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This paper presents a comprehensive potential energy surface (PES) for hydrogen atom addition to and abstraction from 2-methyl-1-butene, 2-methyl-2-butene, and 3-methyl-1-butene and the subsequent ß-scission and H atom transfer reactions. Thermochemical parameters for species on the Ċ

In this paper, the three-phase, two-level Switched -Inductor based Z- Source Inverter (SL-ZSI) and SL based quasi-ZSI (SL-qZSI) are suggested for Renewable Energy Sources (RES) and fuel cell applications. The performance of both the topologies have been analyzed using sine reference based Simple Boost Control Technique (SBCT). The analytical and simulated results are compared with the traditional ZSI. A detailed analysis of topologies and generalized discussion is provided. The analytical and simulated results are verified using MATLAB/Simulink. Further, the proposed converters were simulated and compared with conventional ZSI using SBCT for various shoot through (K) and modulation indices (M).

Induction Motors (IM) are work horse of power industries. Controlling of IM is crucial task in most of the applications. This paper presents implementation of a Variable Frequency Drive (VFD) controller for a three phase induction motor driven by single phase supply on an Arduino platform. The hardware setup involves a rectifier-inverter combination along with a DC link. The present work concentrates on programming the timers of ATMEGA 2560 microcontroller to obtain the required switching pulses. The simulation results of the developed switching control technique with due validation from a hardware setup are presented.

An important aspect of program parallelization is the mapping of concurrent tasks that are a product of the parallelization process to the processors of a parallel machine. A step often over-shadowed by the concurrency detection and the task creation phases but nevertheless as important from the performance perspective and to realize the full benefits of parallelization. The mapping process is driven by two inherent characteristics of the tasks, namely the execution cycle count and the required communication bandwidth. Since these two are independent traits of a program, it is a challenge to find a solution to the mapping problem, that satisfies both these criteria. There is a third aspect involved in the mapping process, called the load balancing, which just means loading the processors of the machine uniformly, and is more connected to the machine topology than the set of tasks involved. This often can be achieved by paying careful attention to the two previous traits of the program. The algorithms to solve this mapping problem and their complexity analyses were presented in an earlier paper and here we focus on the evaluation of these algorithms using an empirical approach using cost equations, with results gathered for different permutations of processor and task count. We also present Topmap a tool that emerged and evolved during the course of our research and assisted us in the data and graph creation, algorithm deployment, data gathering, and analysis phases of our work. Topmap with a few tweaks can be turned in to an infrastructure or a platform for solving a major category of problems based on the graph model.

Parallelization is the process of finding instruction clusters called tasks, which can be executed in concurrent fashion, on multiple processing elements. The objective of parallel execution is to reduce program run time, by overlapping the processing of these tasks. However these tasks are not entirely independent, and generally depend on data generated by peers. One of the objectives of effective parallelization is to limit this inter-task communication, an overhead which can limit the speedup realized through parallelization. Since this inter-task communication cannot be entirely avoided, judiciously mapping the tasks among the processors of a parallel machine, assumes utmost importance. Performance of a parallel program, is also determined by how uniformly the processors of the target machine are loaded with tasks, in situations where the tasks outnumber the processors. This activity is normally referred to as the load balancing. The problem of generating parallel tasks out of a sequential program is well studied, but the related problem of effectively mapping the concurrent tasks, to the processors of a parallel machine, still needs to be researched. This research work involved studying the problem of mapping specific tasks to individual processors, referred to here as the Processor Task Mapping and finding effective solutions. Previous solutions to the mapping problem were non-deterministic, sub-optimal, and incomplete, since their focus was mainly on the task schedules and load balancing criteria and mostly ignoring the communication profile of the tasks to drive the mapping decision. This was the main driving force for taking up our research. We present here the outcomes of this study namely, several efficient graph based algorithms to perform this mapping effectively. These algorithms are general and are applicable to machine topologies of diverse architectures, including the Shared Memory Multiprocessor, Distributed Multiprocessor and the Non-Uniform Memory Access Machines (NUMA), are scalable, deterministic, and produce close to optimal solutions.

The pyrolysis of selected C3 C5 allylic hydrocarbons has been studied using a single-pulse shock tube. A new single-pulse shock tube has been designed and constructed by recommissioning an existing conventional shock tube. This facility enables the investigation of high-temperature chemical kinetics with an emphasis on combustion chemistry. The modifications performed on the existing shock tube are described, and the details of the sampling system to analyze the species concentration using a gas chromatography-mass spectrometry-flame ionization detection (GC-MS with a flame ionization detector) system are also provided. This facility is characterized and validated by performing cyclohexene pyrolysis experiments. Furthermore, the performance of the shock tube is demonstrated by reproducing previous literature measurements on the pyrolysis of isobutene. Postvalidation, this setup is used to study the pyrolysis of trans-2- butene and 2-methyl-2-butene (2M2B). A newly developed mechanism, NUIGMech1.0, is used to simulate the experimental data of propene, isobutene, 2- butene, and 2M2B, allylic hydrocarbon fuels. A description using two different kinetic simulation approaches is provided using our isobutene experiments as a reference. We found no significant differences between the two methods. Additionally, the contribution of different reaction classes on fuel consumption is detailed and the influence of geometry on fuel consumption and first aromatic ring: benzene is discussed. 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. Haitao Lu acknowledges financial support from China Scholarship Council. The authors would also like to acknowledge Dr. Kenji Yasunaga, Dr. Robert Tranter and Prof. Karl Alexander Heufer for their input during the design phase. peer-reviewed 2021-08-17

This paper proposes an optimized Multi-Level Inverter (MLI) topology with symmetrical and asymmetrical DC sources for sustainable energy applications. The proposed MLI has optimized components to reduce size, cost, and installation area in comparison with traditional MLIs. It also improves output power quality by reducing harmonics in the stepped output, and hence it can be used for sustainable energy applications with a grid interface. The proposed inverter is equipped with six switching devices, one clamping diode, and two DC sources. It produces a five-level stepped output when using symmetrical DC sources and a seven-level stepped output when using asymmetrical DC sources. In this topology, the six switching devices are divided into two units, namely the level generator and the polarity generator units, the switches used in the level generator are responsible for producing the required number of levels in the form of rectified stepped output and the switches used in the polarity generator are responsible for converting the rectified stepped waveform to stepped AC output. The simulation results verify the operation of the MLI when fed with linear load with symmetrical and asymmetrical DC sources, and the experimental output results are presented for validation.

This paper proposes an optimized Multi-Level Inverter (MLI) topology with symmetrical and asymmetrical DC sources for sustainable energy applications. The proposed MLI has optimized components to reduce size, cost, and installation area in comparison with traditional MLIs. It also improves output power quality by reducing harmonics in the stepped output, and hence it can be used for sustainable energy applications with a grid interface. The proposed inverter is equipped with six switching devices, one clamping diode, and two DC sources. It produces a five-level stepped output when using symmetrical DC sources and a seven-level stepped output when using asymmetrical DC sources. In this topology, the six switching devices are divided into two units, namely the level generator and the polarity generator units, the switches used in the level generator are responsible for producing the required number of levels in the form of rectified stepped output and the switches used in the polarity generator are responsible for converting the rectified stepped waveform to stepped AC output. The simulation results verify the operation of the MLI when fed with linear load with symmetrical and asymmetrical DC sources, and the experimental output results are presented for validation.

The present situation people with hearing and visual impairment need more support in their physical and psychosocial improvement. Child with visual and hearing impairment is not only face a lot of individual hardships during his premature developing years but also face a many problems and challenges to the responsible adults in his life. The intention of the current examination was to measure the lung capacity of hearing and visually impaired special school children of Karnataka state. Further the level of perception on forced expiratory volume per second and peak expiratory flow volume per minute was also correlated with their actual status. The present study was conducted on four hundred and fourteen (N=414) hearing and visually impaired special school children selected through purposive random sampling technique. The study included adolescents with hearing impairment one hundred and seventy one (N=171) and vision impairment two hundred and forty three (N=243) in male group. Complete subjects were residents of special schools within Karnataka state. Their age ranged between 13 to 18 years. The forced expiratory volume per second and peak expiratory flow volume per minute measurement was done by following the standard procedure. The level of perception on forced expiratory volume per second and peak expiratory flow volume per minute of hearing and visually impaired school children was done using a 3 point likert scale. The forced expiratory volume per second of 13 to 14 years with 2.01 ± 0.48; 2.39 ± 0.46 in 15 to 16 years; and 2.58 ± 0.52 in 17 to 18 years. The peak expiratory flow volume per minute was 290.36 ± 68.99 in 13 to 14 years; 326.95 ± 75.09 in 15 to 16 years; and 352.18 ± 87.00 in 17 to 18 years. On the basis of the findings of the current examination it is concluded that the hearing and visually impaired school going children poor forced expiratory volume per second and peak expiratory flow volume per minute is an indication of lower lung capacity level. Since hearing and visually impaired school going children require to perform their everyday physical exercise at their own, it is imperative to have enough lung capacity. Further, the hearing and visually impaired school children under examination are unable to significantly weak positive linear relationship their lung capacity precisely., {"references":["1.\tAl-Rahamneh, H., Dababseh, M and Eston, R (2013) \"Fitness level of deaf students compared to hearing students in Jordan\", Journal of Physical Education and Sport; Volume- 13(4); PP: 528 – 532. 2.\tBabu, K.R., Mohit, M and Kolekar, D (2015) \"A Comparative Study of Peak Expiratory Flow Rate (PEFR) and BMI in Male and Female Medical Students\", International Journal of Health Sciences and Research; 5(8); PP: 273-278. 3.\tFeng, K., Chen, L., Han, S. M and Zhu, G. J (2011) \"Spirometric Standards for Healthy Children and Adolescents of Korean Chinese in Northeast China\", Journal of Korean Medical Sciences; 26(11); PP: 1469-1473. 4.\tJalili, F., Beiki, Y., Fathizadan, A and Hossini, F (2011) \"The Effect of a Twelve Week Aerobic Exercise Program on Self-Concept among 8 to 10 Years Old Physically and Mentally Disabilities Children\", Australian Journal of Basic and Applied Sciences; 5(10); PP: 1187-1190. 5.\tKobberling, G., Jankowski, L. W and Leger, L (1989) \"Energy Cost of Locomotion in Blind Adolescents\", Adapted Physical Activity Quarterly; 8; PP: 58-67. 6.\tMehta, B., Garg, K., Ambwani, S., Bhandari, B and Bhagat, O.L (2016) \"Peak Expiratory Flow Rate: A Useful Tool for Early Detection of Airway Obstruction in School Children\", Open Medicine Journal; 3; PP:159-165. 7.\tMessan, F., Dansou, P., Amoussou, T., Marqueste, T., Sovi-Guidi, B., Decherchi, P and Tossou, R (2013) \"First Report of FVC and FEV1 Reference Values for Beninese Children Aged 11–16 Years\", Hindawi Publishing Corporation; PP: 1-8. 8.\tMiller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Crapo, R., Enright, P., van der Grinten, C.P.M., Gustafsson, P., Jensen, R., Johnson, D.C., MacIntyre, N., McKay, R., Navajas, D., Pedersen, O.F., Pellegrino, R., Viegi, G and Wanger, J (2005) \"Standardisation of spirometry\", European Respiratory Journal; 26(2); PP: 319-338. 9.\tMoore, V.C (2014) \"Spirometry: step by step\", Breathe practice-focused education for respiratory professionals; 8(3); PP: 233-240. 10.\tRahmani-Nia, F, Damitchi, A, Azizi, M and Hoseini, R. (2011) \"Associations between Self-Perceived and Measured Physical Fitness of Male College Students, World Applied Sciences Journal; 14(9); PP: 1331-1338. 11.\tRiungu, K (2002). \"The effects of Physical Education and Sports program on deaf pupils' health related fitness\", Unpublished Master's Thesis, Kenyatta University, Nairobi, Kenya."]}

Introduction: Dexmedetomidine has been shown to have a myocardial protective effect in off-pump coronary artery bypass patients. However, the same dosage of dexmedetomidine could not elicit a myocardial protective effect in percutaneous coronary intervention patients. The aim of this study was to assess the effect of different doses of dexmedetomidine when used for myocardial protection in percutaneous coronary interventional patients. Methodology: 240 patients (Group D1, treated with dexmedetomidine [n=80]; Group D2, treated with dexmedetomidine [n=80]; and the control group [C; n=80]) were enrolled in the study. Dexmedetomidine was administered over 15 minutes in the respective doses in Groups D1 and D2 at the start of the procedure, while normal saline was given to patients in Group C. Maintenance of dexmedetomidine/NS was started at 0.5 µg/kg/hour in the groups until 30 minutes post-procedure. Creatine phosphokinase (CPK) and CPK-MB, heart rate (HR), mean blood pressure (MAP), and sedation score were noted at baseline (T0), 6 hours (T1), 12 hours (T2), and 24 hours (T3) after the loading dose. Results: MAP and HR significantly decreased in D1 and D2 compared to C (p

The objective of this study is to investigate the effect of compression ratio on combustion characteristics of diesel engine with waste cooking oils methyl ester–diesel blends as fuel. The DI engin...

The standard treatment for high-grade serous ovarian cancer is primary debulking surgery followed by chemotherapy. The extent of metastasis and invasive potential of lesions can influence the outcome of these primary surgeries. Here, we explored the underlying mechanisms that could increase metastatic potential in ovarian cancer. We discovered that FABP4 (fatty acid binding protein) can substantially increase the metastatic potential of cancer cells. We also found that miR-409-3p regulates FABP4 in ovarian cancer cells and that hypoxia decreases miR-409-3p levels. Treatment with DOPC nanoliposomes containing either miR-409-3p mimic or FABP4 siRNA inhibited tumor progression in mouse models. With RPPA and metabolite arrays, we found that FABP4 regulates pathways associated with metastasis and affects metabolic pathways in ovarian cancer cells. Collectively, these findings demonstrate that FABP4 is functionally responsible for aggressive patterns of disease that likely contribute to poor prognosis in ovarian cancer., In ovarian cancer, metastatic phenotype may impact surgical outcomes. Here, the authors show miR-409-3p regulates FABP4 which can increase metastatic potential of ovarian cancer, and treatment with DOPC nanoliposomes containing either miR-409--3p mimic or FABP4 siRNA inhibits tumor progression in mice.

Primary debulking surgery followed by adjuvant chemotherapy is the standard treatment for ovarian cancer. Residual disease after primary surgery is associated with poor patient outcome. Previously, we discovered ADH1B to be a molecular biomarker of residual disease. In the current study, we investigated the functional role of ADH1B in promoting ovarian cancer cell invasiveness and contributing to residual disease. We discovered that ADH1B overexpression leads to a more infiltrative cancer cell phenotype, promotes metastasis, increases the adhesion of cancer cells to mesothelial cells, and increases extracellular matrix degradation. Live cell imaging revealed that ADH1B-overexpressing cancer cells efficiently cleared the mesothelial cell layer compared to control cells. Moreover, gene array analysis revealed that ADH1B affects several pathways related to the migration and invasion of cancer cells. We also discovered that hypoxia increases ADH1B expression in ovarian cancer cells. Collectively, these findings indicate that ADH1B plays an important role in the pathways that promote ovarian cancer cell infiltration and may increase the likelihood of residual disease following surgery.

The gut microbiome is an important determinant for the success of anti-tumor therapies including chemotherapeutics and anti-checkpoint inhibitors. In this study we wanted to leverage Second Genome’s large and curated microbiome database coupled with its proprietary bioinformatics and machine learning tools to discover bioactive peptides from Bifidobacteria that have the potential to drive response to immunotherapy. The genome of Bifidobacterium (B.) breve and B. longum were analyzed for proteins which were potentially secreted, and had unknown functions. 50 peptides were chemically synthesized and then screened in cell based assays for T cell activation and cytokine secretion. In the present study we describe one such novel B. breve-derived 42-aa peptide (SG-3-0020). The peptide stimulated secretion of effector cytokines by in vitro-cultured T cells (IFNg, TNF-a, IL-10 and IL-2) and increased the expression of PD-1 on both CD4+ and CD8+ T cells when stimulated with low-dose anti-CD3 antibody. To identify the binding partners and mechanism of action of the peptide, Mass Spec and Single-cell RNA-seq was used. Mass spec analysis showed that SG-3-05308, a variant of SG-3-0020 binds to a transmembrane glycoprotein of the immunoglobulin superfamily. Silencing this gene via CRISPR-Cas significantly decreased PD1 levels, cell proliferation and IFNg production in human pan T cells. Single cell RNA-seq data showed that SG-3-0020 activates NF-kB signaling and modulates calcium signaling in T cells. The potency of SG-3-0020 was further optimized for binding to activated T cells by using alanine scanning, saturation, and combinatorial mutation libraries using phage display. The results of protein engineering demonstrated that the 13 amino acids from the C-terminus of SG-3-0020 were not critical for binding and a 29-aa long (lacking the C-term) peptide stimulated increased IFNg production in human T cells across multiple human donors in a dose dependent manner. The peptide with the highest potency SG-3-05429 was selected for further understanding of how it interacts with the identified glycoprotein target and activates downstream T cell signaling pathways . Collectively, these data suggest that SG-3-0020’s ability to up-regulate key co-stimulatory and checkpoint molecules on T cells provides a strong rationale for its potential future use in combination with IO. These results validate the capability of the Second Genome drug discovery platform to identify novel microbial peptides/proteins of potential therapeutic relevance in IO and demonstrate a unique approach that can identify microbial derived bioactive molecules involved in modulating immune cell effector functions and/or immune cell differentiation. Citation Format: Michelle Lin, Archana S. Nagaraja, Dhwani Haria, Yuliya Katlinskaya, Divya Ravichandar, Preston Williams, Roberta Hannibal, Todd Z. DeSantis, Bum-Yeol Hwang, Michi Wilcoxon, Toshi Takeuchi, Karim Dabbagh, Preeti Lal, Helena Kiefel. Development and validation of a novel T-cell modulating, microbiome-based peptide for combination with immunotherapy [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P260.

A newly developed detailed chemical kinetic mechanism, NUIGMech1.1, is used to study the pyrolysis of C1 ¿ C7 hydrocarbons at a constant initial fuel concentration in the temperature range 900 ¿ 2000 K. We observe that, for a given reaction time and pressure, fuel pyrolysis does not occur below a certain ¿threshold temperature¿. This phenomenon is explored further in this study by performing rate of production analyses for different fuels. It is observed that pyrolysis is highly sensitive to unimolecular dissociation reactions and that the products of unimolecular dissociation determine the secondary fuel consumption pathways. Furthermore, a minimum progress of reaction factor for the initiation of pyrolysis is established for different fuels over a wide range of residence time (3 ms ¿ 30 min) and partial pressure (0.02 ¿ 2.00 bar) conditions. This limiting factor determines the threshold temperature for the pyrolysis of any alkane or alkene. A computer program is developed based on this concept to calculate the threshold temperature. An application of threshold temperature is also illustrated. The authors would like to acknowledge Science Foundation Ireland for funding via project numbers 15/IA/3177 and 16/SP/3829. The authors would also acknowledge Dr. Charles Westbrook and Prof. Karl Alexander Heufer for fruitful discussions during manuscript preparation. peer-reviewed

Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy. Pexophagy, the specific autophagy of peroxisomes, is downregulated in neurons, and peroxisomes produce more ROS. 2-hydroxypropyl-β-cyclodextrin (HPβCD), an activator of the transcription factor TFEB, which regulates expression of genes involved in autophagy and lysosome function, mitigates damage of pexophagy and decreases ROS production induced by doxorubicin. We conclude that peroxisome-associated oxidative stress induced by doxorubicin may contribute to neurotoxicity, cognitive dysfunction, and accelerated brain aging in cancer patients and survivors. Peroxisomes might be a valuable new target for mitigating neuronal damage caused by chemotherapy drugs and for slowing down brain aging in general.

In this communication, we present a systematic investigation on structural, electric, magnetic and thermoelectric power properties of REMnO3 (RE = Dy, Gd, Eu and Sm) manganites which were prepared using solid-state reaction route. The samples exhibit orthorhombic crystal structure with Pbnm space group. Rietveld analysis of x-ray diffraction (XRD) data shows that the unit cell volume increases with increase in ionic radii of the rare earth ion, $r_{\text {RE}}$ . The particle size was calculated from the scanning electron microscope (SEM) images. The estimated particle size is observed to decrease with increasing ionic radii of the rare earth ions. All samples exhibit insulating behaviour and display immeasurably high resistivity at low temperatures. Magnetization studies indicate that the samples display a transition in the low temperature region. Magnetization data also reveals that antiferromagnetic behaviour is observed for all samples. Thermoelectric power results show that large thermoelectric power is seen for these manganites. Thermoelectric power of high-temperature region was successfully analysed using small polaron hopping (SPH) model.

The current research focuses on dry sliding wear behaviour of end of life CRT panel glass and BN reinforced hybrid magnesium matrix composite fabricated through powder metallurgy route. CRT panel glass percentage (5, 10 & 15 wt %) and particle size (10, 30 & 50 μm) are varied to find its effect on wear performance and BN solid lubricant is added at a fixed level of 2%. Increase in reinforcement content and particle size decreases the wear rate whereas the opposite trend is found for coefficient of friction. ANOVA results reveal that all of the considered parameters significantly influence the response parameters. Taguchi based GRA is used for multi objective optimization and the worn surface SEM analysis is also performed.

// Yasmin A. Lyons 1 , Sunila Pradeep 1 , Sherry Y. Wu 1 , Monika Haemmerle 1 , Jean M. Hansen 1 , Michael J. Wagner 1 , Alejandro Villar-Prados 1 , Archana S. Nagaraja 1 , Robert L. Dood 1 , Rebecca A. Previs 1 , Wei Hu 1 , Yang Zhao 4 , Duncan H. Mak, 7 Zhilan Xiao 5 , Brenda D. Melendez 5 , Gregory A. Lizee 5 , Imelda Mercado-Uribe 6 , Keith A. Baggerly 4 , Patrick Hwu 5 , Jinsong Liu 6 , Willem W. Overwijk 5 , Robert L. Coleman 1 and Anil K. Sood 1,2,3 1 Departments of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3 Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of Bioinformatics and Computational Biology, Division of Quantitative Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 5 Department of Melanoma Medical Oncology-Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 6 Department of Pathology, Division of Pathology and Laboratory Medicine, Section of Gynecologic Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 7 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence to: Anil K. Sood, email: // Keywords : adaptive resistance, anti-VEGF therapy, tumor associated macrophages, tumor microenvironment, CSF1R inhibition Received : April 18, 2017 Accepted : July 20, 2017 Published : August 24, 2017 Abstract Anti-angiogenesis therapy has shown clinical benefit in patients with high-grade serous ovarian cancer (HGSC), but adaptive resistance rapidly emerges. Thus, approaches to overcome such resistance are needed. We developed the setting of adaptive resistance to anti-VEGF therapy, and performed a series of in vivo experiments in both immune competent and nude mouse models. Given the pro-angiogenic properties of tumor-associated macrophages (TAMs) and the dominant role of CSF1R in macrophage function, we added CSF1R inhibitors following emergence of adaptive resistance to anti-VEGF antibody. Mice treated with a CSF1R inhibitor (AC708) after anti-VEGF antibody resistance had little to no measurable tumor burden upon completion of the experiment while those that did not receive a CSF1R inhibitor still had abundant tumor. To mimic clinically used regimens, mice were also treated with anti-VEGF antibody and paclitaxel until resistance emerged, and then a CSF1R inhibitor was added. The addition of a CSF1R inhibitor restored response to anti-angiogenesis therapy, resulting in 83% lower tumor burden compared to treatment with anti-VEGF antibody and paclitaxel alone. Collectively, our data demonstrate that the addition of a CSF1R inhibitor to anti-VEGF therapy and taxane chemotherapy results in robust anti-tumor effects.

Herein, we successfully fabricated vertically aligned silicon nanowires (Si NWs) via an electrochemical etching of n-type (100) silicon at different high current densities. The morphology of the prepared Si NWs was studied using SEM, FFT analysis and WSxM software. From FTIR spectroscopy analysis, the silicon dangling bonds of the as-prepared Si NWs layer have large amount of hydrogen to form weak Si H bonds. The blue shift was observed in Photoluminescence due to decrease in the size of silicon crystallites, the crystallite size in the Si NWs varied from 5.9 nm to 4.8 nm depending on the current density. The contact angle varied from 74.7° to 149.1°. From the wettability studies, the surface nature of the Si NWs was converted from hydrophilic to hydrophobic when the current density increased. The obtained Si NWs were used as an anode in lithium ion cell. The charge capacity of the anode is ~ 3452.47 mAh g− 1 at the first cycle with the coulombic efficiency over 85.8%, and faded to 1134.34 mAh g− 1 with coulombic efficiency over 81.6% after the 12th cycle at a current rate of 1C. Scanning electron microscopy and selected area electron diffraction are performed to study the morphology and crystalline structure of the anode, respectively. The dislocation density decreased from 46.2 × 1015 m− 2 to 0.06 × 1015 m− 2 and the surface area decreased from 1.5 × 103 μm2 to 0.05 × 103 μm2 with cycle number increased from 1 to 102 whereas the band gap increased from 2.2 eV to 2.9 eV. The above observations are well correlated.

The optimal time to treat neuropathic (Charcot) arthropathy of the ankle and peritalar joint is controversial because of the various treatment options available and the variable results reported in published studies. We sought to determine the outcome of hind foot arthrodesis with stable internal fixation in patients with different Eichenholtz stages of arthropathy. We prospectively studied patients with substantial disabilities caused by neuropathic arthropathy in deformed, unstable ankle and peritalar joints, with or without ulcerations, who had undergone treatment from July 2007 to December 2012. All patients underwent ankle arthrodesis, autologous iliac crest bone grafting, and subtalar joint arthrodesis, with or without talonavicular joint arthrodesis, fixed internally with an intramedullary hindfoot nail, with or without an additional plate or cancellous screws. Of the 33 enrolled patients, 9 (27.3%) had stage I, 13 (39.4%) had stage II, and 11 (33.3%) had stage III Charcot arthropathy. The cause of arthropathy was diabetes mellitus in 25 (75.8%) patients. The duration of symptoms ranged from 1 to 120 (median 7) months. The mean follow-up period was 40 (range 12 to 76) months and did not differ markedly among the groups. The hindfoot scores, rate of salvage or amputation, or complication rates did not differ significantly across Eichenholtz stage. For the patients with stage I, II, and III, the preoperative hindfoot score was 50, 49, and 48, respectively (p = .9). The corresponding postoperative scores were 68, 68, and 70 (p = .5). We found no evidence that the effectiveness of hindfoot arthrodesis by stable fixation varied across the Eichenholtz stage of Charcot arthropathy involving ankle and peritalar joint. Furthermore, we found that stable internal fixation and bone grafting using a hindfoot nail results in an 84.84% union rate and salvages the unstable and disabled foot in 90.9% of patients with ankle and peritalar Charcot arthropathy.