High throughput determination of sequence-function relationships in protein and RNA

Thesis (Ph.D.)--University of Washington, 2016-06

Understanding conceptual schemas: exploring the role of application and IS domain knowledge

Although information systems (IS) problem solving involves knowledge of both the IS and application domains, little attention has been paid to the role of application domain knowledge. In this study, which is set in the context of conceptual modeling, we examine the effects of both IS and application domain knowledge on different types of schema understanding tasks: syntactic and semantic comprehension tasks and schema-based problem-solving tasks. Our thesis was that while IS domain knowledge is important in solving all such tasks, the role of application domain knowledge is contingent upon the type of understanding task under investigation. We use the theory of cognitive fit to establish theoretical differences in the role of application domain knowledge among the different types of schema understanding tasks. We hypothesize that application domain knowledge does not influence the solution of syntactic and semantic comprehension tasks for which cognitive fit exists, but does influence the solution of schema-based problem-solving tasks for which cognitive fit does not exist. To assess performance on different types of conceptual schema understanding tasks, we conducted a laboratory experiment in which participants with high- and low-IS domain knowledge responded to two equivalent conceptual schemas that represented high and low levels of application knowledge (familiar and unfamiliar application domains). As expected, we found that IS domain knowledge is important in the solution of all types of conceptual schema understanding tasks in both familiar and unfamiliar applications domains, and that the effect of application domain knowledge is contingent on task type. Our findings for the EER model were similar to those for the ER model. Given the differential effects of application domain knowledge on different types of tasks, this study highlights the importance of considering more than one application domain in designing future studies on conceptual modeling.

Emergent temporal behaviour and collaborative work

Although collaboration manifestly takes place in time, the role of time in shaping the behaviour of collaborations, and collaborative systems, is not well understood. Time is more than clock-time or the subjective experience of time; its effects on systems include differential rates of change of system elements, temporally non-linear behaviour and phenomena such as entrainment and synchronization. As a system driver, it generates emergent effects shaping systems and their behaviour. In the paper we present a systems view of time, and consider the implications of such a view through the case of collaborative development of a new university timetabling system. Teasing out the key temporal phenomena using the notion of temporal trajectories helps us understand the emergent temporal behaviour and suggests a means for improving outcomes.

Synthesis and evaluation of N1-substituted-3-propyl-1,4-benzodiazepine-2-ones as cholecystokinin (CCK2) receptor ligands

A novel synthetic approach towards N1-alkylated 3-propyl-1,4-benzodiazepines was developed in five synthetic steps from 2-amino-4-chlorobenzophenone, in which the N-oxide 4 served as a key intermediate. The structure-activity relationship optimization of this 3-prophyl-1,4-benzodiazepine template was carried out on the N1-position by selective alkylation reactions and resulted in a ligand with an improved affinity on the cholecystokinin (CCK2) receptor. The N-allyl-3-propyl-benzodiazepine 6d displayed an affinity towards the CCK2 (CCK-B) receptor of 170 nM in a radiolabelled receptor-binding assay. The anxiolytic activity of this allyl-3-propyl-1,4-benzodiazepine 6d was subsequently determined in in-vivo psychotropic assays. This novel ligand had ED50 values of 4.7 and 5.2 mg kg-1 in the black and white box test and the x-maze, respectively, and no significant sedation/muscle relaxation was observed.

Transients and asymptotics of natural gradient learning

We analyse natural gradient learning in a two-layer feed-forward neural network using a statistical mechanics framework which is appropriate for large input dimension. We find significant improvement over standard gradient descent in both the transient and asymptotic phases of learning.

TAP for parity check error correcting codes

We employ the methods presented in the previous chapter for decoding corrupted codewords, encoded using sparse parity check error correcting codes. We show the similarity between the equations derived from the TAP approach and those obtained from belief propagation, and examine their performance as practical decoding methods.

Public key cryptography and error correcting codes as Ising models

We employ the methods of statistical physics to study the performance of Gallager type error-correcting codes. In this approach, the transmitted codeword comprises Boolean sums of the original message bits selected by two randomly-constructed sparse matrices. We show that a broad range of these codes potentially saturate Shannon's bound but are limited due to the decoding dynamics used. Other codes show sub-optimal performance but are not restricted by the decoding dynamics. We show how these codes may also be employed as a practical public-key cryptosystem and are of competitive performance to modern cyptographical methods.

Magnetization enumerator for LDPC codes - a statistical physics approach

We propose a method based on the magnetization enumerator to determine the critical noise level for Gallager type low density parity check error correcting codes (LDPC). Our method provides an appealingly simple interpretation to the relation between different decoding schemes, and provides more optimistic critical noise levels than those reported in the information theory literature.

The unique complexity of social phenomena and the uses of social science knowledge

The assertion about the peculiarly intricate and complex character of social phenomena has, in much of social discourse, a virtually uncontested tradition. A significant part of the premise about the complexity of social phenomena is the conviction that it complicates, perhaps even inhibits the development and application of social scientific knowledge. Our paper explores the origins, the basis and the consequences of this assertion and asks in particular whether the classic complexity assertion still deserves to be invoked in analyses that ask about the production and the utilization of social scientific knowledge in modern society. We refer to one of the most prominent and politically influential social scientific theories, John Maynard Keynes' economic theory as an illustration. We conclude that, the practical value of social scientific knowledge is not necessarily dependent on a faithful, in the sense of complete, representation of (complex) social reality. Practical knowledge is context sensitive if not project bound. Social scientific knowledge that wants to optimize its practicality has to attend and attach itself to elements of practical social situations that can be altered or are actionable by relevant actors. This chapter represents an effort to re-examine the relation between social reality, social scientific knowledge and its practical application. There is a widely accepted view about the potential social utility of social scientific knowledge that invokes the peculiar complexity of social reality as an impediment to good theoretical comprehension and hence to its applicability.

Acquirer and owner perceptions of technology integration:the South African case

Developing countries are subject to the same global pressures as their developed counterparts but have additional domestic challenges that may place them at a significant, and perhaps insurmountable, disadvantage. However, technology still offers them the opportunity to participate in the international economy. Difficult conditions in their countries do not absolve managers from formulating and implementing technology policies that can make their firms globally competitive. At a macro-economic level, a number of broad developmental issues impact on the use of technology in developing countries. The subject of this paper is to examine the challenge for South African firms in their efforts to master technology, despite internal and external difficulties. Owners of technology need to consider the local context when supplying their technology to developing markets. The paper aims to investigate the views of technology recipients by examining the perceptions of South African managers regarding technology integration in a manufacturing environment. A number of technology suppliers were also interviewed in order to obtain their opinions on the issues raised by the technology acquirers. The importance of different factors in integrating technology is studied in relation to managers ’ abilities to control these variables. An importance-control grid framework is used to identify critical parameters and to assess how they can be managed in a complex environment.

The fallacy of integration:work and non-work in professional services

Many organisations are encouraging their staff to integrate work and non-work, but a qualitative study of young professionals found that many crave greater segregation rather than more integration. Most wished to build boundaries to separate the two and simplify a complex world. Where working practices render traditional boundaries of time and space ineffective, this population seems to create new idiosyncratic boundaries to segregate work from non-work. These idiosyncratic boundaries depended on age, culture and life-stage though for most of this population there was no appreciable gender difference in attitudes to segregating work and non-work. Gender differences only became noticeable for parents. A matrix defining the dimensions to these boundaries is proposed that may advance understanding of how individuals separate their work and personal lives. In turn, this may facilitate the development of policies and practices to integrate work and non-work that meet individual as well as organisational needs.

Web-based expert systems:benefits and challenges

Convergence of technologies in the Internet and the field of expert systems have offered new ways of sharing and distributing knowledge. However, there has been a general lack of research in the area of web-based expert systems (ES). This paper addresses the issues associated with the design, development, and use of web-based ES from a standpoint of the benefits and challenges of developing and using them. The original theory and concepts in conventional ES were reviewed and a knowledge engineering framework for developing them was revisited. The study considered three web-based ES: WITS-advisor - for e-business strategy development, Fish-Expert - for fish disease diagnosis, and IMIS - to promote intelligent interviews. The benefits and challenges in developing and using ES are discussed by comparing them with traditional standalone systems from development and application perspectives. © 2004 Elsevier B.V. All rights reserved.