Modeling, identification, and application of multilayer polypyrrole conducting polymer actuators

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2007.Includes bibliographical references.Experiments were performed using commercially available, self-contained, multilayer polypyrrole (PPy) actuators to develop low-order lumped parameter models of actuator electrical, mechanical, and electromechanical behavior. Experimental data were processed using system identification techniques. Both grey box and black box models were identified. The grey box model consisted of a first order electrical network that was linearly and algebraically coupled to a second order viscoelastic model. The black box model incorporated a third order Box-Jenkins structure and achieved model to data residues comparable to the grey box model. When utilizing validation data, the grey box model showed very good performance for loads in the range of 0.5 to 3 N. Overall, the results of system identification experiments suggested that low order, lumped parameter models were adequate to describe the gross behavior of multilayer actuators. An online identification scheme was developed for monitoring polymer electrical impedance and thereby monitoring the degradation state of an actuator. This identification was performed successfully using recursive least squares and least squares for a discrete impedance model.(cont.) Experimental validation data, spanning more than 5 hours of continuous operation, were collected and analyzed. A final contribution of this research was the application PPy linear actuators to a custom-designed humanoid foot. Four linear conducting polymer actuators were used to obtain multifunctional behavior of the overall foot. Jacobian analysis of stiffness and damping was performed for the design. Simulations illustrated that PPy actuators through the use of appropriate electrical excitation can modulate their stiffness characteristics as a function of time to match a desired force versus length relationship.by Thomas W. Secord.S.M

Design and application of a cellular, piezoelectric, artificial muscle actuator for biorobotic systems

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 219-227).One of the foremost challenges in robotics is the development of muscle-like actuators that have the capability to reproduce the smooth motions observed in animals. Biological muscles have a unique cellular structure that departs from traditional electromechanical actuators in several ways. A muscle consists of a vast number of muscle fibers and, more fundamentally, sarcomeres that act as cellular units or building blocks. A muscle's output force and displacement are the aggregate effect of the individual building blocks. Thus, without using gearing or transmissions, muscles can be tailored to a range of loads, satisfying specific force and displacement requirements. These natural actuators are desirable for biorobotic applications, but many of their characteristics have been difficult to reproduce artificially. This thesis develops and applies a new artificial muscle actuator based on piezoelectric technology. The essential approach is to use a subdivided, cellular architecture inspired by natural muscle. The primary contributions of this work stem from three sequential aims. The first aim is to develop the operating principles and design of the actuator cellular units. The basic operating principle of the actuator involves nested flexural amplifiers applied to piezoelectric stacks thereby creating an output length strain commensurate with natural muscle. The second aim is to further improve performance of the actuator design by imparting tunable stiffness and resonance capabilities. This work demonstrates a previously unavailable level of tunability in both stiffness and resonance. The final aim is to showcase the capabilities of the actuator design by developing an underwater biorobotic fish system that utilizes the actuators for resonance-based locomotion. Each aspect of this thesis is supported by rigorous analysis and functional prototypes that augment broadly applicable design concepts.by Thomas William Secord.Ph.D

The C-terminus of Bienertia sinuspersici Toc159 contains essential elements for its targeting and anchorage to the chloroplast outer membrane

Most nucleus-encoded chloroplast proteins rely on an N-terminal transit peptide (TP) as a post-translational sorting signal for directing them to the organelle. Although Toc159 is known to be a receptor for specific preprotein TPs at the chloroplast surface, the mechanism for its own targeting and integration into the chloroplast outer membrane is not completely understood. In a previous study, we identified a novel TP-like sorting signal at the C-terminus (CT) of a Toc159 homolog from the single-cell C4 species, Bienertia sinuspersici. In the current study, we have extended our understanding of the sorting signal using transient expression of fluorescently-tagged fusion proteins of variable-length, and with truncated and swapped versions of the CT. As was shown in the earlier study, the 56 residues of the CT contain crucial sorting information for reversible interaction of the receptor with the chloroplast envelope. Extension of this region to 100 residues in the current study stabilized the interaction via membrane integration, as demonstrated by more prominent plastid-associated signals and resistance of the fusion protein to alkaline extraction. Despite a high degree of sequence similarity, the plastid localization signals of the equivalent CT regions of Arabidopsis thaliana Toc159 homologs were not as strong as that of the B. sinuspersici counterparts. Together with computational and circular dichroism analyses of the CT domain structures, our data provide insights into the critical elements of the CT for the efficient targeting and anchorage of Toc159 receptors to the dimorphic chloroplasts in the single-cell C4 species.published_or_final_versio

Randomized phase II trial of bevacizumab plus everolimus versus bevacizumab alone for recurrent or persistent ovarian, fallopian tube or peritoneal carcinoma: An NRG oncology/gynecologic oncology group study

PURPOSE: Bevacizumab (BV) monotherapy leads to compensatory upregulation of multiple signaling pathways, resulting in mTOR activation. We evaluated combining BV and everolimus (EV), an mTOR kinase inhibitor, to circumvent BV-resistance in women with recurrent or persistent ovarian, fallopian tube or primary peritoneal cancer (OC). PATIENTS AND METHODS: Eligible OC patients had measurable (RECIST1.1) or detectable disease, 1-3 prior regimens, performance status (PS) 0-2, and no prior m-TOR inhibitor. All patients received BV 10 mg/kg IV every 2wks. Patients were randomized (1:1) to oral EV (10 mg daily) or placebo stratified by platinum-free interval (PFI), measurable disease and prior BV. Primary endpoint was progression-free survival (PFS); secondary endpoints included safety and response. RESULTS: 150 patients were randomized to BV with (n = 75) and without (n = 75) EV. Arms were well-balanced for age (median 63: range 28-92), PS (0: 73%, 1-2: 27%), prior regimens (1: 37%, 2: 47%, 3: 16%), prior BV (11%), PFI (<6mos: 65%) and measurable disease (81%). The BV + EV vs BV median PFS was 5.9 vs 4.5 months (hazard ratio [HR] 0.95 (95% CI, 0.66-1.37, p = 0.39)). Median OS was 16.6 vs 17.3 months (HR 1.16 (95% CI, 0.72-1.87, p = 0.55). Objective measurable responses were higher with BV + EV (22% vs 12%). Study removal due to toxicity was higher with BV + EV (29% vs 12%). Toxicity (≥grade 3) from BV + EV were "other GI (mucositis)" (23 vs 1%) and "metabolic/nutrition" (19 vs. 7%); common ≥ grade 2 toxicities with BV + EV were cytopenia, nausea, fatigue and rash. CONCLUSION: The combination regimen (BV + EV) did not significantly reduce the hazard of progression or death relative to BV and was associated with higher rates of adverse events and study discontinuation when compared to BV alone

A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer

© 2020 American Association for Cancer Research Inc.. All rights reserved. Purpose: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (GþC) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. Patients and Methods: Patients received either GþC (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). Results: Of 100 patients treated, 51 received GþC and 49 received TC, of which 27 crossed over to GþC. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the GþC and TC groups, respectively; P ¼ 0.07). However, the 6-month PFS rate was significantly higher in the GþC group (37% vs. 11% in TC group; P ¼ 0.003). The incidence of grade 3 or higher toxicity was similar in GþC and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the GþC group. Conclusions: Although this trial did not show superiority for PFS of GþC versus TC, the 6-month PFS increased in GþC treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection

Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer

Tumor hypoxia is associated with adverse outcome in many malignancies. The goal of this study was to determine if elevated expression of carbonic anhydrase IX (CAIX), a biomarker of hypoxia, predicts for recurrence in early-stage cervical cancer. The charts of all patients with early-stage cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988–2001 were reviewed. Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remained disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/intensity of staining. Outcome, as measured by freedom from recurrence (FFR), distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastases as first site of failure (5-year FFDM 50%) than patients with only +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p = 0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expression is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment

Introduction: looking beyond the walls

In its consideration of the remarkable extent and variety of non-university researchers, this book takes a broader view of ‘knowledge’ and ‘research’ than in the many hot debates about today’s knowledge society, ‘learning age’, or organisation of research. It goes beyond the commonly held image of ‘knowledge’ as something produced and owned by the full-time experts to take a look at those engaged in active knowledge building outside the university walls

A novel business strategies framework of do-it-yourself practices in logistics to minimise environmental waste and improve performance

The transportation sector is consuming a high quantity of oil and producing air pollution, CO2 and allergies, as well as promoting the storage of goods in traditional warehouses. It is not only creating waste and environmental pollution but also increasing temperature, air pollution and low rainfall. The present study intends to uncover and understand the challenges of logistic infrastructure as well as how the adoption of do-it-yourself (DIY) business strategies is useful to encourage those practices and technology which are useful in transforming the logistic infrastructure into an eco-friendly environment. The DIY focuses on purposely utilising digital technologies to increase the engagement and involvement of customers in businesses. Moreover, DIY enables organisations to produce products and services that are highly demanded and have high acceptability. After doing an extensive literature review, the enablers of DIY are identified, and empirical investigation has been conducted. The analysis of the study provides a business strategies framework of DIY which would help the logistics managers in the proper implementation of the DIY practices to minimise negative environmental impact and improve business performance