Rational Design of Multifunctional Polymer Therapeutics for Cancer Theranostics

Although anti-angiogenic agents offer great therapeutic potential, preclinical and clinical studies suggest that these agents, used as monotherapies, have a delayed onset of activity and may have only limited effects on advanced malignancies. Multimodality targeted polymer therapeutics that include anti-angiogenic agents and chemotherapeutics offer the potential for improved efficacy and diminished toxicity in the treatment of cancer and other angiogenesis-dependent diseases. We have recently designed and characterized novel combined anti-angiogenic and antitumor polymer–drug conjugates that target both the tumor and its microenvironment. These conjugates include combined anti-angiogenic and chemotherapeutic drugs, such as TNP-470 and paclitaxel, respectively. Several conjugates also incorporate bisphosphonates as targeting moieties for bone metastases and osteosarcomas or RGD peptidomimetics that target integrins overexpressed on tumor endothelial cells and several tumor cells. Using molecular imaging techniques, we have successfully established dormant and fast-growing tumor mouse models to intravitally non-invasively follow-up tumor progression and response to novel polymer therapeutics. Our results point at our polymer therapeutics as novel bi-specific conjugates targeting both the tumor epithelial and endothelial compartments, warranting their use on a wide spectrum of primary as well as metastatic tumors. The use of these novel architectures will potentially shed light on the molecular mechanisms underlying tumor dormancy and hopefully transform cancer into a chronically-manageable disease.     

The Art of Organic Synthesis in the Age of Automation

Recent progress in the automation of chemical synthesis is part of a broad ongoing trend that is based on incorporating machine learning algorithms to improve automated performance in different tasks. However, what are the implications on the art of organic synthesis? Will robotic chemists replace us in the next 50–100 years? Will they be able to outperform a master organic chemist in the study of mechanisms, the development of new reactions, the optimization of reaction conditions, catalysts, or synthetic routes? What would be our role as human chemists in this automation revolution? In this essay, these questions will be reflected upon through the progress in the synthesis of strychnine since 1954.     

Competencies for managing change

Organisational changes are recognised as a specific project type that can benefit from the application of project management skills, tools and techniques. Associated with this trend is evidence of rivalry in the marketplace between Project Managers and Change Managers concerning who should be managing business change. And these are not the only contenders. Corporate executives and senior managers, although they may engage the assistance of both Project Managers and Change Managers, generally see themselves as taking the leading roles in managing major organisational changes and transformations. As such endeavours are most likely to take the form of programs, comprising multiple projects across the organization, Program Managers are seen by some as being most likely to be responsible for managing organisational change initiatives. This paper reports on research undertaken to explore the differences in approach and practice of Project, Program and Change Managers as a basis for determining the competencies required to effectively manage change initiatives.     

On the exploitation of CDF based wireless scheduling

Channel-aware scheduling strategies – such as the CDF scheduler (CS) algorithm – provide an effective mechanism for utilizing the channel data rate for improving throughput performance in wireless data networks by exploiting channel fluctuations. A highly desired property of such a scheduling strategy is that its algorithm is stable, in the sense that no user has incentive “cheating” the algorithm in order to increase his/hers channel share (on the account of others). Considering a single user we show that no such user can increase his/hers channel share by misreporting the channel capacity. In contrast, considering a group of users, we present a scheme by which coordination allows them to gain permanent increase in both their time slots share and in their throughput at the expense of others, by misreporting their rates. We show that for large populations consisting of regular and coordinated users in equal numbers, the ratio of allocated time slots between a coordinated and a regular user converges to e − 1 ≈ 1.7. Our scheme targets the very fundamental principle of CS (as opposed to just attacking implementation aspects), which bases its scheduling decisions on the Cumulative Distribution Function (CDF) of the channel rates reported by users. Our scheme works both for the continuous channel spectrum and the discrete channel spectrum versions of the problem. Finally, we outline a modified CDF scheduler immune to such attacks.     

The Technology of Ammonia Plants

Abstract

There are 105 large-scale plants in successful operation in virtually every corner of the globe. There are 20 more in various stages of design, engineering, or construction. Their capacities range from 600 to 1800 tons a day. These large-scale plants, and 20 earlier smaller Kellogg units, account for approximately half of the world's ammonia production today.     

Executive Growth Along the Adult Development Curve.

This article describes how principles of adult psychological development can inform executive coaching. An adult developmental perspective is used to identify key transformational tasks of adulthood that help shape executive role functioning. The correlation of psychological competencies with leadership competencies is outlined in more detail for the roles of senior vice president and executive vice president. Coaching case material is used to further illustrate how consultants can use an adult developmental framework to better align organizational life with personal strivings for meaning and growth. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A structured interview for the assessment of the Five-Factor Model of Personality.

The authors report on the psychometric properties of a new semistructured interview, the Structured Interview for the Five-Factor Model of Personality (SIFFM; T J. Rull & T A. Widiger, 1997). The SIFFM assesses major dimensions of the five-factor model (FFM) as well as trait facets for each dimension. Analyses of data obtained from both nonclinical and clinical participants support the reliability and validity of SIFFM scores. Specifically, SIFFM scores were reliable across raters, were internally consistent and relatively stable over time, and were correlated with scores from related measures (e.g., personality, personality disorders). The authors discuss the need for and attractiveness of an interview-based measure of the FFM in assessing normal and dysfunctional personality traits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measurements and simulations of thermal comfort: a synagogue in Tel Aviv,Israel

This study illustrates the utility of empirical and digital methodologies in examining the question to which degree an architect who lives and builds in one distinctive geographic and climatic region adapts his sacred architecture design to a different climatic region. Specifically, we analysed the thermal comfort in a Synagogue in Tel Aviv, Israel, designed by a renowned Swiss architect in 1996. The morphological analyses, actual measurements, and computerized energy simulations show that the synagogue exhibits high thermal discomfort during the hot-humid summers in Tel Aviv. The results of morphological analyses and simulations also show thermal discomfort in the synagogue during Tel Aviv's mild winters. When simulating the synagogue as if built in Switzerland, the results also show high thermal discomfort. Thus, the design of this synagogue did not necessarily consider climate conditions. However, the design does exhibit attentiveness and sensitivity to symbols and faith requirements.     

To bridge or to bond? Diverse social connections in an IS project team

Although research has shown that knowledge sharing among project team members is crucial for project performance, achieving knowledge sharing is still challenging. This problem is especially salient in IS project teams. Such teams are temporary organizations that may not progress through the necessary team formation cycle, yet are expected to produce intangible outcomes in a limited time. In this paper, we investigate how bonding and bridging social capital influence knowledge sharing and project performance. Bonding could facilitate cohesiveness within a team and lead a team to achieve project goals. Bridging could facilitate access to various beneficial resources beyond the boundary of a project team, increasing creativity and innovation. However, bridging is costly and can obstruct project performance. Our findings suggest that team members with high bonding social capital are more likely to share their knowledge with their team. Bonding and intention to share knowledge also positively affect project performance. Conversely, bridging social capital can contribute to project performance only through the mediating effect of bonding. This research contributes to theory by empirically examining the two types of social capital and their interdependence, as predictors of knowledge sharing and subsequently project performance. Project managers should form teams composed of members with diverse social connections and consider the balance between bonding and bridging within a team to control the potential disadvantageous effects of bridging social capital.     

A cascade boost-switched-capacitor-converter - two level inverter with an optimized multilevel output waveform

Two structures, a switched-capacitor (SC)-based boost converter and a two-level inverter, are connected in cascade. The dc multilevel voltage of the first stage becomes the input voltage of the classical inverter, resulting in a staircase waveform for the inverter output voltage. Such a multilevel waveform is close to a sinusoid; its harmonics content can be reduced by multiplying the stage number of the SC converter. The output low-pass filter, customary after a two-level inverter, becomes obsolete, resulting in a small size of the system, as the SC circuit can be miniaturized. Both stages are operated at a high switching frequency, resulting in a high-frequency inverter output, as required by some industrial applications. A Fourier analysis of the output waveform is performed. The design is optimized with reference to the nominal duty-cycle for obtaining the minimum total harmonic distortion. Simulations and experiments on two prototypes, one with a five-level output and one with a seven-level output, confirm the theoretical analysis.