scholarly journals Transparency in Human-Machine Mutual Action

2021 ◽  
Vol 33 (5) ◽  
pp. 987-1003
Author(s):  
Hiroto Saito ◽  
Arata Horie ◽  
Azumi Maekawa ◽  
Seito Matsubara ◽  
Sohei Wakisaka ◽  
...  
Keyword(s):  
Sense Of Self ◽  
Single Agent ◽  
Design Guidelines ◽  
Design Approach ◽  
Physical Abilities ◽  
Machine Systems ◽  
Further Development ◽  
System Designs ◽  
Mutual Action ◽  
At Will

Recent advances in human-computer integration (HInt) have focused on the development of human-machine systems, where both human and machine autonomously act upon each other. However, a key challenge in designing such systems is augmenting the user’s physical abilities while maintaining their sense of self-attribution. This challenge is particularly prevalent when both human and machine are capable of acting upon each other, thereby creating a human-machine mutual action (HMMA) system. To address this challenge, we present a design framework that is based on the concept of transparency. We define transparency in HInt as the degree to which users can self-attribute an experience when machines intervene in the users’ action. Using this framework, we form a set of design guidelines and an approach for designing HMMA systems. By using transparency as our focus, we aim to provide a design approach for not only achieving human-machine fusion into a single agent, but also controlling the degrees of fusion at will. This study also highlights the effectiveness of our design approach through an analysis of existing studies that developed HMMA systems. Further development of our design approach is discussed, and future prospects for HInt and HMMA system designs are presented.

GEIS 39: Phase II trial of nabpaclitaxel for the treatment of patient with multiply relapsed/refractory desmoplastic small round cell tumor (DSRCT) and Ewing sarcoma (EwS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11529-11529
Author(s):  
Jaume Mora ◽  
Mariona Suñol ◽  
Nadia Hindi ◽  
Alicia Castañeda ◽  
Andrés Redondo ◽  
...  
Keyword(s):  
Single Agent ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Free Survival ◽  
Pediatric Solid Tumors ◽  
Meaningful Activity ◽  
Common Grade ◽  
Central Pathology ◽  
Grade 3 ◽  
Further Development

11529 Background: Nab-paclitaxel (albumin-bound paclitaxel) has shown preclinical activity against pediatric solid tumors. Preclinical data in EwS PDX models suggested high activity of nab-paclitaxel in tumors expressing high-levels of SPARC. Tumoral SPARC facilitates the accumulation of albumin in the tumor and increases the effectiveness of albumin-bound paclitaxel. Nab-paclitaxel utilizes albumin to deliver paclitaxel via caveolin-mediated endocytosis which is expressed in the EwS cells surface. We hypothesized that SPARC can be a predictive biomarker for nab-paclitaxel in EwS and DSRCT that could potentially be relevant for a better design of clinical trials and personalized treatments using nab-paclitaxel. Methods: Main endpoint of GEIS-39 was the overall response rate (ORR) assessed by RECIST 1.1 criteria with centralized pathology and imaging review. Secondary objectives included safety according to the CTCAE 4.0 criteria. Patients aged ≥ 6 months and ≤ 40 years, with relapsed/refractory DSRCT were eligible after having received at least one previous poly-chemotherapy line; EwS must have received at least two standard chemotherapy lines. Prior taxane therapy was accepted. Central pathology review selected for tumors with > Grade 3 (intense and diffuse) expression of SPARC by immunohistochemistry to be eligible. Nab-paclitaxel was administered as follows: age ≥ 21 and ≤ 40 years: 125 mg/m2 days 1, 8 and 15 in cycles of 28 days; age ≥ 6 months and ≤ 20 years: 240 mg/m2 days 1, 8 and 15 in cycles of 28 days. A 30% ORR was anticipated with a sample size of 25 patients needed to test the hypothesis. Stopping rule was set at 1 response within the first 16 treated pts. If 5 or more successes were observed in 25 pts, the results of the trial will warrant further investigation. Results: Twenty-nine patients were enrolled from June 2017 until October 2019, 11 DSRCT and 18 EwS. Median age was 32 years (range 14-69), and 5 females and 24 males were included, having received a median of 3 previous systemic treatment lines. Patients received a median of 3 cycles of nab-paclitaxel (range 1-17). In the EwS cohort an ORR of 33.3% (all partial responses, median duration 2 months) and 16.7% of stabilizations were achieved. No objective responses were observed among DSRCT pts, but 27.3% of pts achieved a stabilization. Overall, median progression free survival was 2.8 months and median overall survival 12.1 months, with no significant differences between DSRCT and EwS cohorts. Most common grade 3 toxicities were neutropenia (20.7%) and diarrhea (10.3%). Conclusions: Single agent nab-paclitaxel in biomarker selected EwS patients, but not in DSRCT, provided clinically meaningful activity that deserves further development. Nab-paclitaxel had a manageable adverse event profile. Clinical trial information: 2016-002464-14.

Smart Optimization of Machine Systems Using Hierarchical Genotype Representations

1999 ◽  
Author(s):  
Masataka Yoshimura ◽  
Kazuhiro Izui
Keyword(s):  
Structural Design ◽  
Hierarchical Structures ◽  
Optimization Methods ◽  
Optimization Method ◽  
Design Problems ◽  
Design Variables ◽  
The Hierarchical Structure ◽  
Machine Systems ◽  
System Designs ◽  
Crossover And Mutation

Abstract Design problems for machine products are generally hierarchically expressed. With conventional product optimization methods, it is difficult to concurrently optimize all design variables of portions within the hierarchical structure. This paper proposes a design optimization method using genetic algorithms containing hierarchical genotype representations, so that the hierarchical structures of machine system designs are exactly expressed through genotype coding, and optimization can be concurrently conducted for all of the hierarchical structures. Crossover and mutation operations for manipulating the hierarchical genotype representations are also developed. The proposed method is applied to a machine-tool structural design to demonstrate its effectiveness.

題目設定引導設計邏輯發展之教學研究

建築學報 ◽  
2021 ◽  
Vol 116 (116-1) ◽  
pp. 055-061
Author(s):  
江梓瑋 江梓瑋
Keyword(s):  
Design Thinking ◽  
Design Method ◽  
Design Approach ◽  
Design Studio ◽  
Design Development ◽  
Specific Design ◽  
Direct Design ◽  
Operation Process ◽  
Thinking Process ◽  
Further Development

<p>傳統的建築設計課程皆以每學期幾次不同題型的設定，期望在設計操作的反復練習中，幫助操作者探索合適的操作方法並從中建立設計邏輯。設計題目的設定規範了操作的方向與期望的成果，但因設計發展並沒有既定的步驟與方法，常因個人經驗與所選擇設計方式的不同，導致過於感性的思維模式，也造就了理性建築設計教學的挑戰。此研究針對題目設定與設計邏輯的關係，試圖避開操作者可預期的結果，並藉過程中不同階段性的操作設定，試圖建立一種設計邏輯發展的依據。</p> <p>&nbsp;</p><p>Traditionally, architecture design studio requires few exercises per semester for students to practice design method and develop design thinking. As design exercises often direct design approach and also establish expectation of outcome, there is no guaranty procedure or design method to follow in order to achieve the best outcome. Since design development heavily based on experience of operation and choice of approach, sensible thinking process is often involved and sets challenge for rational architectural pedagogy. This research aims to exam the design thinking process of students by setting up specific design exercise to avoid predictable operation process, in order to direct specific design approach according to established guidance for further development. </p> <p>&nbsp;</p>

A phase I pharmacokinetic (PK) and molecular pharmacodynamic (PD) study of the combination of two anti-EGFR therapies, the monoclonal antibody (MAb) cetuximab (C) and the tyrosine kinase inhibitor (TKI) gefitinib (G), in patients (pts) with advanced colorectal (CRC), head and neck (HNC) and non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3006-3006 ◽  
Author(s):  
J. Baselga ◽  
P. Schöffski ◽  
F. Rojo ◽  
H. Dumez ◽  
F. J. Ramos ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Single Agent ◽  
Gene Profiling ◽  
Clinical Activity ◽  
Skin Biopsies ◽  
Grade 3 ◽  
Development Methods ◽  
Further Development ◽  
Profiling Analysis ◽  
Different Doses

3006 Background: C and G are two anti-EGFR agents with different mechanisms of action. We had previously shown a synergistic effect combining the two agents in preclinical models (Matar et al, Clin Cancer Res 2004). This study aims to explore safety, PK and PD changes in tumor and skin at different doses of C/G to define the recommended dose (RD) for further development. Methods: pts were treated at the RD of weekly iv C (400 mg/m2 initial dose, 250 mg/m2 weekly) and oral daily G (250 mg/d) as single agents (5 pts each) and in successive cohorts of combined C/G (3–6 pts each): C (320/200) / G (100), C (400/250) / G (100), C (400/250) / G (250), C (320/200) / G (500) & C (400/250) / G (500) (ongoing). Dose escalation depended on dose limiting toxicity (DLT) rate during the first 28 d. Pre- & on-treatment steady-state (14 d) tumor & skin biopsies were obtained and have been evaluated by IHC for total (t) and phospho (p)-EGFR, p-MAPK, p-Akt, proliferation (Ki67), p27 expression and apoptosis by TUNEL. Gene profiling analysis is ongoing. Results: 35 pts have been treated so far: 20 CRC, 13 HNC & 2 NSCLC; median KI 90 % (70–100); median age 60 years (38–80); 24 males, 11 females. DLTs occurred in 3 pts: 1 pt with G alone with reversible ILD; 1 pt with G (250) / C (400/250) with reversible deafness & 1 pt with G (500) / C (320/200) with grade 3 anorexia and nausea. There were 1 CR (HNC) and 5 PRs (CRC) in the C/G cohorts, and 1 PR (CRC) in the C cohort. Overall, 5 out of 9 (56%) pts with CRC treated in the C/G cohorts presented a PR. PD studies show superior inhibition of p-EGFR, p-MAPK and p-Akt, reduction of proliferation and increased apoptosis (all p values <0.05) in the tumors of pts treated with C/G compared with the single agent cohorts. PK evaluation shows no PK interactions with the 2 drugs. Conclusions: This combination of an anti-EGFR MAb (C) and a TKI (G) is feasible at the RD of both agents. Our findings show encouraging clinical activity, especially in CRC, and superior PD signaling inhibition with the combination without any significant PK interaction. Combined anti-EGFR therapy deserves further evaluation. [Table: see text]

A Design Method for Shape Memory Alloy Actuators Accounting for Cyclic Shakedown With Constrained Allowable Strain

2010 ◽  
Author(s):  
WonHee Kim ◽  
Brian M. Barnes ◽  
Jonathan E. Luntz ◽  
Diann E. Brei
Keyword(s):  
Design Method ◽  
Mechanical Strain ◽  
High Energy ◽  
Design Guidelines ◽  
Design Approach ◽  
High Energy Density ◽  
Interface Position ◽  
Design Variables ◽  
Graphical Design ◽  
Actuation Strain

The high energy density actuation potential of SMA wire is tempered by conservative design guidelines set to mitigate complex factors such as functional fatigue (shakedown). Shakedown causes problems of stroke loss and interface position drift between the system and the SMA wire under higher stress levels if the wire does not undergo a pre-installation shakedown procedure. Limiting actuation strain has been reported as reducing shakedown as well as increasing fatigue life. One approach to limit actuation strain is using a mechanical strain limiter which sets a fixed Martensite strain position — useful for the development of in-device shakedown procedures which eliminates time consuming pre-installation shakedown procedures. This paper presents a new graphical design approach for SMA wire actuators which accounts for shakedown with the use of mechanical strain limiters to enable higher stress designs to maximize actuator performance. Experimental data on the effect of strain limiters along with stroke and work density contours form the basis for the new graphical design method. For each independent mechanical strain limiter, the maximum of the individual post-shakedown austenite curves at a range of applied stress are combined into a conglomerate stabilization design curve. These curves over a set of mechanical strain limiters provide steady state performance prediction for SMA actuation, effectively decoupling the shakedown material performance from design variables that affect the shakedown. The use and benefits of this new design approach are demonstrated with a common constant force actuator design example. This new design approach, which accounts for shakedown, supports design of SMA actuators at higher stresses with more economical use of material/power, and enables the utilization of strain limiters for cost saving in-device shakedown procedures.

scholarly journals Research on the channels for creation and development of high-quality “green manufacturing” brands — a case study of Xiamen

2021 ◽  
Vol 257 ◽  
pp. 03081
Author(s):  
Xiujuan Zhang ◽  
Pingyuan Zhao
Keyword(s):  
Manufacturing Industry ◽  
Rapid Development ◽  
Green Manufacturing ◽  
Design Guidelines ◽  
Ecological Impacts ◽  
High Quality ◽  
The World ◽  
Global Vision ◽  
Further Development

as the manufacturing industry gains momentum around the world, the conflicts between its rapid development and the accompanying consumption of materials, discharge of wastes and ecological impacts spiral. Governments around the world have explored measures and made achievements in alleviating the dual pressures from economic growth and environmental degradation. As for the overall trend of the manufacturing industry, creating and developing “green manufacturing” brands is the only way for the manufacturing industry to achieve further development. It is of great significance to design guidelines for green manufacturing from the angle of branding, the green notion provides more profundity and the soul to brands, ensuring sustainable development of brands. The development of green brands in Xiamen has adopted a global vision and related to the local realities, which would provide lessons for high-quality development of green manufacturing brands in other places.

Phase I study of oral gemcitabine prodrug (LY2334737) alone and in combination with erlotinib in patients (pts) with advanced solid tumors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2576-2576
Author(s):  
S. Koolen ◽  
P. O. Witteveen ◽  
I. Garcia-Ribas ◽  
S. Callies ◽  
V. Andre ◽  
...  
Keyword(s):  
Single Agent ◽  
Hypovolemic Shock ◽  
Hepatic Function ◽  
Maximum Tolerated Dose ◽  
Continual Reassessment ◽  
Proportional Increase ◽  
Grade 3 ◽  
Ecog Ps ◽  
Dose Levels ◽  
Further Development

2576 Background: LY2334737 (LY) is an orally available valproic acid prodrug of gemcitabine that was developed to overcome the extensive first-pass metabolism of gemcitabine to 2',2'-difluorodeoxyuridine (dFdU). The objectives of this study were to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and pharmacokinetics (PK) of LY as monotherapy and in combination with erlotinib. Methods: Eligible pts had ECOG PS < 2 and adequate hematologic, renal and hepatic function. In Arm A, LY was given daily for 14 days in a 3-week cycle. Pts assigned to Arm B also received erlotinib daily 100 mg continuously. Dose escalation was based on observed toxicity and the modified continual reassessment method (mCRM). The dose was maximally increased by 100% depending on the toxicity observed in the previous cohort. PK of LY, gemcitabine, dFdU and intracellular metabolites were determined. Results: 33 pts (21 m, 12 f, median age 60 yrs (range 24–81)) were treated at 5 different dose-levels (range 5–50 mg/day). Pts received a median of 3 cycles (range 2–17). Three out of 7 pt treated with 50 mg experienced 5 dose limiting toxicities (DLT). DLTs observed at 40 and 50 mg include fatigue (4 pt), thrombocytopenia (1 pt), GGT elevation (1 pt), AST/ALT elevation (1 pt), fever (1 pt), and pulmonary embolism (1 pt). One death was possibly related to LY intake. This pt, treated with 40 mg LY, developed on day 15 dyspnea, hypovolemic shock, and suddenly died. No grade 3 or 4 toxicities were reported at dose-levels < 40 mg. The most common adverse events were fatigue, vomiting, nausea, pyrexia, anorexia, and diarrhea. Two pts with mesothelioma were stable for > 9 months. One pt with refractory prostate cancer presented a PSA CR as assessed by investigator. The PK show dose-proportional increase in exposure of both LY and gemcitabine. Both LY and gemcitabine are rapidly cleared, thus no accumulation occurs. The metabolite dFdU accumulates due to its long half life. Conclusions: LY displays linear PK. The dose level of 50-mg is non-tolerable and 40-mg is being confirmed as the MTD as single agent and in combination with 100 mg erlotinib. Antitumor activity warrants further development. Pt accrual is ongoing. [Table: see text]

Nāgārjuna (c. AD 150–200)

2018 ◽  
Author(s):  
Mark Siderits
Keyword(s):  
East Asia ◽  
South India ◽  
Sense Of Self ◽  
Ultimate Truth ◽  
Profound Influence ◽  
Inherent Nature ◽  
Further Development ◽  
In Virtue Of ◽  
Ultimate Nature ◽  
Insight Into

Nāgārjuna was the first Buddhist philosopher to articulate and seek to defend the claim that all things are empty, that is, devoid of their own essential nature. A native of South India, as the founder of the Madhyamaka school of Mahāyāna Buddhism he exerted a profound influence on the further development of Buddhist thought in South and East Asia. When he claimed that all things are empty, he denied that anything exists solely in virtue of its own inherent nature. If, as all Buddhists hold, existents only arise in dependence on other existents, then nothing may be said to have a determinate nature apart from its relations to other things. Yet prior developments in Buddhist philosophy had presumably shown that anything lacking an independent nature is a conceptual fiction and not ultimately real. Thus if all things are empty, nothing is ultimately real. Still Nāgārjuna claimed not to be a nihilist. Emptiness is rather the defeat of all metaphysical theories, all attempts at grasping the ultimate nature of reality – including nihilism. Insight into emptiness is said to free us from our tendency conceptually to construct an ultimate truth, a tendency that bolsters our sense of self. Thus realization of emptiness is, Nāgārjuna held, required in order to attain full liberation from the suffering caused by clinging.

scholarly journals Smart education framework

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Kadir Alpaslan Demir
Keyword(s):  
Information Technologies ◽  
Literature Search ◽  
Design Approach ◽  
Education Systems ◽  
Layered Architecture ◽  
Wide Range ◽  
Education Design ◽  
Smart Education ◽  
System Designs ◽  
And Training

AbstractAdvances in information technologies present opportunities for novel approaches, methods, and tools for new or improved education and training practices. Furthermore, these technologies are enabling a shift in the education paradigm. Based on an investigation of a wide range of information technologies supporting smart education, we developed a Smart Education Framework. The framework conceptually structures the information technologies in a layered architecture. We also developed a smart education design approach based on the framework. Furthermore, we show how to use the framework and design approach to develop a specific course or lecture design. To validate the smart education framework, we examined smart education systems reported in the literature. To identify smart education systems, we conducted a systematic literature search. The literature search results show that the smart education framework has the ability to describe smart education systems. This study contributes to the current literature with a smart education framework. The smart education framework will guide future smart education system designs.

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