Source Of New Ideas Research Articles

Applying science to drug discovery

Scientists and science in the pharmaceutical industry rely heavily on the more academically orientated basic research carried out at Universities, for first of all training, but also as a source of new ideas and approaches to drug discovery. Progress in the discovery and development of novel therapeutics benefits from a healthy alliance with, and the output from, more basic research institutions, and the reverse is also true, with many advances in understanding of physiological and pathological processes being as the result of the application of novel targeted molecules. To illustrate this, some examples related to the themes of this meeting from my experiences in three different companies will be described. The first involves a metabolic angle in the unravelling of the mechanism of the novel anti-anginal agent ranolazine. The second describes the application of detailed knowledge of insulin structure and action to then use recombinant approaches to design novel molecules to be able to offer the Type I (insulin-dependent) diabetic patient therapies allowing a more physiological treatment regime, and also the further application of learned technology to then discover a means of harnessing the potential of GLP-1 (glucagon-like polypeptide 1) for treating Type II (non-insulin-dependent) diabetes. The last illustrates how findings of novel binding sites on glycogen phosphorylase and glucokinase as the result of drug discovery programmes have led to increased understanding of these key metabolic enzymes and also potential new therapies for Type II diabetes.

Applying science to drug discovery

Scientists and science in the pharmaceutical industry rely heavily on the more academically orientated basic research carried out at Universities, for first of all training, but also as a source of new ideas and approaches to drug discovery. Progress in the discovery and development of novel therapeutics benefits from a healthy alliance with, and the output from, more basic research institutions, and the reverse is also true, with many advances in understanding of physiological and pathological processes being as the result of the application of novel targeted molecules. To illustrate this, some examples related to the themes of this meeting from my experiences in three different companies will be described. The first involves a metabolic angle in the unravelling of the mechanism of the novel anti-anginal agent ranolazine. The second describes the application of detailed knowledge of insulin structure and action to then use recombinant approaches to design novel molecules to be able to offer the Type I (insulin-dependent) diabetic patient therapies allowing a more physiological treatment regime, and also the further application of learned technology to then discover a means of harnessing the potential of GLP-1 (glucagon-like polypeptide 1) for treating Type II (non-insulin-dependent) diabetes. The last illustrates how findings of novel binding sites on glycogen phosphorylase and glucokinase as the result of drug discovery programmes have led to increased understanding of these key metabolic enzymes and also potential new therapies for Type II diabetes.

Are Small Firms Really Less Productive?

Small and medium-sized establishments (SMEs) account for a large proportion of industrial employment and production in almost all countries. Moreover, the recent literature emphasizes the role SMEs play in nurturing entrepreneurship and generating new products and processes. Although SMEs could be a source of new ideas and innovations, there are substantial productivity differences between small and large establishments. In this paper, we analyze three sources of productivity differentials: technical efficiency, returns to scale, and technical change. Our analysis on the creation, survival, and growth of new establishments in Turkish manufacturing industries in the period 1987–1997 shows that all these three factors play a very important role in determining the survival probability and growth prospects of new establishments.

Wavelet and Multiscale Methods

The Wavelet and Multiscale Methods workshop, organized by Albert Cohen (Paris), Wolfgang Dahmen (Aachen), Ronald A. DeVore (Columbia) and Angela Kunoth (Bonn) was held July 11–17, 2004. A central objective was to bring together leading researchers working in a variety of different areas where multiscale phenomena play an intrinsic role regarding the theoretical understanding of the problems as well as the numerical solution concepts. This meeting was well attended with over 45 participants with a broad geographic representation from all continents. With only very few exceptions, the most prominent representers of the respective fields participated in the workshop. The main link being multiscale concepts, the overall audience was certainly less homogeneous than in most other workshops. In order to provide a solid ground for discussions and synergies, thirteen of the twenty six talks were longer survey-style lectures by leading experts who had been contacted by the organizers prior to the meeting. The following topics were addressed in the survey-type lectures: Several adaptive wavelet schemes for fluid flow problems were presented with varying emphasis on analysis and numerical realization. This included combinations of statistical and multiresolution concepts for understanding turbulence. Such approaches were complemented by a “two-scale” point of view where the concept of “residual free bubbles” allows one to model the influence of unresolved scales to the resolved ones, initiating vivid discussions about a possible combination of these approaches. From the perspective of nonlinear approximation, best N -term approximation in corresponding anisotropic function spaces was discussed, which is another important component in adaptive solution concepts in this context. Another focal point was the quasi – sparse or data – sparse representation of global operators, for instance, via wavelet bases or through concepts like hierarchical matrices. On one hand, this was shown to lead to new shape – optimization techniques as well as to significant advancements of adaptive wavelet methods for boundary integral equations. On the other hand, hierarchical matrix concepts were seen to make extremely high dimensional problems of a certain separable structure numerically tractable. In fact, problems of high spatial dimension were treated in the context of quantum chemistry centering upon the solution of the Schrödinger equation for many particles as one of the grand challenges of the future. Here compression and sparse grid techniques were again complemented by theoretical investigations of the regularity of eigensolutions which provides the foundation of the potential success of such numerical methods. Anisotropy is also a key issue in modern image compression techniques. The “wedgelet” concept was presented as a way of extending approximation libraries in combination with image encoding and model selection techniques. Moreover, the meeting adequately reflected through several talks some very recent advances in the currently highly active area of Mathematical Learning Theory, where new synergies between approximation theory and statistics are just emerging. In particular, wavelet techniques have now led to new universal estimators in a model free regression context where the universality could be achieved through nonlinear approximation concepts. Regarding the inhomogeneity of the participants' research fields, in order to maintain a high level of attendance and interest throughout the meeting, the topics of the lectures were deliberately mixed. This created a very open atmosphere and essentially all talks were followed by extensive discussions revealing a number of unforeseen connections between seemingly different subjects. The reaction of the participants during the meeting clearly indicated that the combination of different areas was very well perceived as a source of new ideas and perspectives. New collaborations were initiated and already existing cooperations partly across disciplines were pursued on a visibly intense level.

The neutral theory of biodiversity and biogeography and Stephen Jay Gould

Neutral theory in ecology is based on the symmetry assumption that ecologically similar species in a community can be treated as demographically equivalent on a per capita basis—equivalent in birth and death rates, in rates of dispersal, and even in the probability of speciating. Although only a first approximation, the symmetry assumption allows the development of a quantitative neutral theory of relative species abundance and dynamic null hypotheses for the assembly of communities in ecological time and for phylogeny and phylogeography in evolutionary time. Although Steve Gould was not a neutralist, he made use of ideas of symmetry and of null models in his science, both of which are fundamental to neutral theory in ecology. Here I give a brief overview of the current status of neural theory in ecology and phylogeny and, where relevant, connect these newer ideas to Gould's work. In particular, I focus on modes of speciation under neutrality, particularly peripheral isolate speciation, and their implications for relative species abundance and species life spans. Gould was one of the pioneers in the study of neutral models of phylogeny, but the modern theory suggests that at least some of the conclusions from these early neutral models were premature. Modern neutral theory is a remarkably rich source of new ideas to test in ecology and paleobiology, the potential of which has only begun to be realized.

Novel Avidin-like Protein from a Root Nodule Symbiotic Bacterium, Bradyrhizobium japonicum

Bradyrhizobium japonicum is an important nitrogenfixing symbiotic bacterium, which can form root nodules on soybeans. These bacteria have a gene encoding a putative avidin- and streptavidin-like protein, which bears an amino acid sequence identity of only about 30% over the core regions with both of them. We produced this protein in Escherichia coli both as the full-length wild type and as a C-terminally truncated core form and showed that it is indeed a high affinity biotin-binding protein that resembles (strept)avidin structurally and functionally. Because of the considerable dissimilarity in the amino acid sequence, however, it is immunologically very different, and polyclonal rabbit and human antibodies toward (strept)avidin did not show significant cross-reactivity with it. Therefore this new avidin, named bradavidin, facilitates medical treatments such as targeted drug delivery, gene therapy, and imaging by offering an alternative tool for use if (strept)avidin cannot be used, because of a deleterious patient immune response for example. In addition to its medical value, bradavidin can be used both in other applications of avidin-biotin technology and as a source of new ideas when creating engineered (strept)avidin forms by changing or combining the desired parts, interface patterns, or specific residues within the avidin protein family. Moreover, the unexpected discovery of bradavidin indicates that the group of new and undiscovered bacterial avidin-like proteins may be both more diverse and more common than hitherto thought.

Learning from Diversity: A Theoretical Exploration

Public‐sector organizations tend to be more racially and ethnically diverse than private‐sector organizations, leading to the challenge of enhancing heterogeneous work group effectiveness. Recent work suggests that a group's “diversity perspective,” or set of beliefs about the role of cultural diversity, moderates diverse group performance. One perspective, the integration and learning perspective, argues that heterogeneous groups function better when they believe that cultural identities can be tapped as sources of new ideas and experiences about work. However, simply holding the integration and learning perspective may not be sufficient. Research on general group learning has shown that it requires particular behaviors and cognitive frames. This article integrates recent work on diversity perspectives with long‐standing research on team learning to propose a conceptual model of learning in culturally diverse groups. It suggests that both the integration and learning perspective and more generic learning frames and skills must be present.

Self-experimentation as a source of new ideas: Ten examples about sleep, mood, health, and weight

Little is known about how to generate plausible new scientific ideas. So it is noteworthy that 12 years of self-experimentation led to the discovery of several surprising cause-effect relationships and suggested a new theory of weight control, an unusually high rate of new ideas. The cause-effect relationships were: (1) Seeing faces in the morning on television decreased mood in the evening (> 10 hrs later) and improved mood the next day (> 24 hrs later), yet had no detectable effect before that (0-10 hrs later). The effect was strongest if the faces were life-sized and at a conversational distance. Travel across time zones reduced the effect for a few weeks. (2) Standing 8 hours per day reduced early awakening and made sleep more restorative, even though more standing was associated with less sleep. (3) Morning light (1 hr/day) reduced early awakening and made sleep more restorative. (4) Breakfast increased early awakening. (5) Standing and morning light together eliminated colds (upper respiratory tract infections) for more than 5 years. (6) Drinking lots of water, eating low-glycemic-index foods, and eating sushi each caused a modest weight loss. (7) Drinking unflavored fructose water caused a large weight loss that has lasted more than 1 year. While losing weight, hunger was much less than usual. Unflavored sucrose water had a similar effect. The new theory of weight control, which helped discover this effect, assumes that flavors associated with calories raise the body-fat set point: The stronger the association, the greater the increase. Between meals the set point declines. Self-experimentation lasting months or years seems to be a good way to generate plausible new ideas.

Learning from concepts and ideas presented in Process Safety Progress

AbstractMagazine articles, such as those in Process Safety Progress (PSP), are a source of new ideas as well as old ideas restated and emphasized. While busy schedules increasingly interfere with getting the most out of these types of information sources, studying such published papers should not be given a low priority. Presented below are ideas and thoughts (some garbage, some gems) on a variety of subjects from just one such issue (September 2001 of PSP). They include: comments on the probabilistic nature of electrostatic ignition, the domino effect in explosion scenarios, MY Tree analysis of accidents, an argument from the viewpoint of the industrial ecosystem in support of a fault data bank, the prescriptiveness of performance‐based standards, the applicability of HAZOP to analogous systems different in scale and purpose, keys to a good HAZOP and a good FMEA, an argument in support of a universal effort to improve process safety by throwing cash at the hazards, initiator/enabler concepts, the use of a bar chart to effectively present the relative effectiveness of strategies used to control overall plant risk, the flammability diagram: a living, pulsating thing, and comments on the relationship between minimum ignition energy and turbulence.

The promise of new ideas and new technology for improving teaching and learning.

There have been enormous advances in our understanding of human learning in the past three decades. There have also been important advances in our understanding of the nature of knowledge and new knowledge creation. These advances, when combined with the explosive development of the Internet and other technologies, permit advances in educational practices at least as important as the invention of the printing press in 1460. We have built on the cognitive learning theory of David Ausubel and various sources of new ideas on epistemology. Our research program has focused on understanding meaningful learning and on developing better methods to achieve such learning and to assess progress in meaningful learning. The concept map tool developed in our program has proved to be highly effective both in promoting meaningful learning and in assessing learning outcomes. Concept mapping strategies are also proving powerful for eliciting, capturing, and archiving knowledge of experts and organizations. New technology for creating concept maps developed at the University of West Florida permits easier and better concept map construction, thus facilitating learning, knowledge capture, and local or distance creation and sharing of structured knowledge, especially when utilized with the Internet. A huge gap exists between what we now know to improve learning and use of knowledge and the practices currently in place in most schools and corporations. There are promising projects in progress that may help to achieve accelerated advances. These include projects in schools at all educational levels, including projects in Colombia, Costa Rica, Italy, Spain, and the United States, and collaborative projects with corporate organizations and distance learning projects. Results to date have been encouraging and suggest that we may be moving from the lag phase of educational innovation to a phase of exponential growth.

Beyond Cold War Paradigms for Science and Democracy

Steve Fuller has been a virtual one-man industry in the field of Science and Technology Studies for more than a decade. In Social Epistemology, he outlined an ambitious programme for remaking the emerging interdisciplinary field into a catalyst for transforming the academy, for the purpose of serving the greater good. Mixing equal measures of constructivist sociology, analytical philosophy, and post-modern theory, Fuller has tried to explain how the disciplinary structure of the field must change in order to reform the academy and society. Key to his concept of social epistemology is the idea that philosophical prescriptions are empty if they do not specify the social conditions for their implementation. Seeing most philosophical talk as empty, and most sociology as too reticent to prescribe, Fuller sought to shake up the accepted division of labour so that a vigorous, theoretically-informed science policy could be developed. He founded a journal, also called Social Epistemology, to encourage interaction among scholars who engage with these issues. Reactions to Fuller's early work generally praised it as a source of new ideas, but questioned his style and methods. To many, his approach to history was particularly off-putting. He did not rely upon detailed case studies to make palatable his theoretical musings an emerging standard for the field that he saw as misguided. He even suggested that experimental psychology should replace history as the preferred science of science.1 Many believed that his policy advice presupposed the standpoint of a benevolent but authoritarian philosopher-king. It is a credit to his willingness to engage critics that he went on to develop a more democratic

Notes from the editor

The first thing most readers will notice about this issue is the cover, which is colored blue this time and is adorned by a clock to signify “Taking Temporality Seriously,” the first article in the issue. After noting the cover (admiringly, I hope) and browsing through the table of contents, readers are hereby invited to shift their attention briefly to the roster of editorial board members inside the cover. There they will see something new: as previewed in an earlier “Notes from the Editor,” an executive committee of the Review's editorial board is now in operation. The six-member executive committee consists of four representatives of major subfields of the discipline (Darren Davis for American politics, James Morrow for international politics, Kirstie McClure for political theory, and Sven Steinmo for comparative politics) and two “at-large” members (Neta Crawford and Robert Goodin). The members of the executive committee are intended to be the “first among equals” in advising me on matters of editorial policy, serving as an initial sounding board and source of new ideas before issues come to the full editorial board. Pertinent examples of the committee's responsibilities include planning an appropriate commemoration of the Review's centenary and revisiting our procedures for handling “Forum” submissions and responses. Executive committee members also constitute a first line of defense in advising me when issues arise concerning particular manuscripts, though such responsibilities tend to be infrequent and, given the diversity of the manuscripts we consider, are fairly widely dispersed among members of the editorial board rather than confined solely to executive committee members. All editorial board members also share responsibility for “recruiting” promising manuscripts within their areas of expertise, but executive committee members are asked to be especially active in this regard. Finally, it is the executive committee that will, early in 2003, review the performance of our editorial office in general and my performance as editor in particular. With the latter point in mind, I want to emphasize (1) that I selected the executive committee with an eye toward diversity of various sorts (substantive, theoretical, methodological, demographic, and so on), and (2) that the executive committee consists of individuals with whom I have not been associated professionally or personally, apart from my familiarity with their work, and with whom I have no more than a nodding acquaintance, if that.

Policy transfer and reversal: customary land registration from Africa to Melanesia

AbstractIdeas and laws about land titling were transferred from East Africa to Melanesia in the 1950s and 1960s. There they provoked a nationalist reaction, and new sources of ideas became influential: from other South Pacific countries in the 1970s, from economic theory in the 1980s, and from the World Bank in the 1990s. Research has cast doubt on the effectiveness of earlier schemes, though little has emerged in Melanesia to take their place. This article analyses the process as one of failed ‘policy transfer’ in which the beneficiaries of the policy may see it quite differently from the government and donors who promote it. Copyright © 2002 John Wiley & Sons, Ltd.

Chemistry in the 21st century. A central science or a "back office" technical activity?

Abstract The science of chemistry underlies all of our work in the environmental area and in the new technologies exemplified by materials science and molecular physics. For these areas to progress, chemistry must continue to be a creative and innovative source of new ideas rather than just a handmaiden for currently identified problems in these closely allied areas of study.

Introduction

Introduction Stephanie Beswick and Jay Spaulding The countries of the Horn of Africa—Ethiopia, Eritrea, Somalia, and Sudan—are among the continent's most troubled. These nations have been at war for decades. Ethiopia has been a postimperial nation-state for only a few years, yet during this interval has suffered famine, Marxist revolutionary dictatorship, liberation, and famine once again, in quick succession. Eritrea fought a long, hard war to achieve its recent and fragile freedom from Ethiopia and continues to be vulnerable to its larger, more powerful neighbor. Somalia has fallen into a fractious state of almost continuous warfare since its political disintegration in 1991; the fragments of the former nation are currently presided over by powerful clan families. The longest war anywhere in the Horn is that in South Sudan. There, a desperately fought war for independence from Islamic fundamentalists of the northern government has intermittently sputtered and raged since 1955, resulting in the cumulative death of millions. In all times of political upheaval, women suffer in ways that differ significantly from those of their male counterparts. This volume presents the first compilation of papers concerning the lives of women in the conflict zones of the Horn of Africa. During the last half-century, women's studies has proven to be a very rich source of new ideas for the social sciences and humanities; indeed, it would be hard to name a rival in the stimulation of innovative theoretical approaches, original research and analytical methodologies, and the mobilization of new forms of evidence toward comprehension of the human condition. One consequence of this very efflorescence of [End Page 1] thought, however, has been the branching of the young scholarly tradition into many pathways, not all of which seem to lead toward a single destination. A fundamental question concerns the conceptualization of the discipline's human context; some scholars have chosen to focus fairly emphatically upon women as women, while others have preferred to interpret women's lives as integral parts of various other forms of social reality. A second important set of decisions confronts those who opt for the latter approach: what scale of conceptualization and which disciplinary techniques and intellectual discourses are appropriate for the understanding of each to ensure that the very diverse situations are considered? Does one traverse the interior landscape of an individual mind, the story of the events of a person's life, or the many levels of women's cultural and historical engagement in family, class, ethnic, national, and religious traditions? Any scholar may well find the research agenda to be guided, when not dictated, by the forms of relevant evidence that happen to be available; the product of such an effort cannot fail to reflect its empirical roots, and it is not always easy to achieve a sense of what is commensurate among works rooted in radically diverse evidential bases. For all the reasons indicated, it has not been easy for women's studies to achieve consensus concerning which situations, out of all of women's experiences, are properly to be compared with which others. The papers contributed to this special issue of Northeast African Studies devoted to women and the study of women, each excellent in its own way, inevitably reflect at least some of the fertile tensions and the diversity that characterize the discipline as a whole. In his painstaking historiographical survey of writings by and about women in Ethiopia, Belete Bizuneh exposes a range of themes that also, in broad strokes, characterizes the literature of the region as a whole. Dominant among these is fragmentation; despite promising but tentative pioneer works by a younger generation of Ethiopian scholars, it is not easy to find a relevant women's literature for Ethiopia. A distinct if related theme is that of oblique reference. Much of what may indeed be read about women in Ethiopia must be extracted, through an intellectual process resembling reconstructive surgery, from studies devoted primarily to something else. A third important theme is the disproportionate [End Page 2] weight of foreign scholarship throughout; at this time, the demand for an intellectual commitment to women in the Horn is clearly of primarily alien origin. While this circumstance need...

Location and the Innovation Performance of Commercial GIS Companies

This paper looks at the role of firm size, location, and in‐house research and development (R&D) in the innovation performance of U.S. firms in the commercial geographic information systems (GIS) industry. Data from a survey of 300 GIS firms are presented. The results suggest that innovation‐intensity varies directly with in‐house R&D spending (scaled as a proportion of company sales), but inversely with company size (total employment). Significant regional variations in the innovation performance of GIS firms are identified. It is argued that the geography of innovation is influenced by the spatial distribution of young and/or small firms, in that R&D‐productivity is found to vary inversely with company size. An important finding is that creative inputs to support innovation are almost evenly divided between internal and external sources. A surprising result is that the academic community is not viewed as a particularly important source of new ideas for innovative firms. The paper concludes with a discussion of the implications of the survey data for future empirical work on the GIS sector.

Personalization of Supermarket Product Recommendations

We describe a personalized recommender system designed to suggest new products to supermarket shoppers. The recommender functions in a pervasive computing environment, namely, a remote shopping system in which supermarket customers use Personal Digital Assistants (PDAs) to compose and transmit their orders to the store, which assembles them for subsequent pickup. The recommender is meant to provide an alternative source of new ideas for customers who now visit the store less frequently. Recommendations are generated by matching products to customers based on the expected appeal of the product and the previous spending of the customer. Associations mining in the product domain is used to determine relationships among product classes for use in characterizing the appeal of individual products. Clustering in the customer domain is used to identify groups of shoppers with similar spending histories. Cluster-specific lists of popular products are then used as input to the matching process. The recommender is currently being used in a pilot program with several hundred customers. Analysis of results to date have shown a 1.8% boost in program revenue as a result of purchases made directly from the list of recommended products. A substantial fraction of the accepted recommendations are from product classes new to the customer, indicating a degree of willingness to expand beyond present purchase patterns in response to reasonable suggestions.

Confessions of an Occupational Therapist Who Became a Detective

This life history of an occupational therapist traces her evolution from a biomedical technician to a ‘detective’, who searches for new ideas that will support clinical practice and enable the profession to achieve its potential contribution to humankind. These ideas focus on ‘homo occupacio’, the occupational human: an agent who sets goals, makes choices and becomes competent through engagement in occupation. Concepts such as motivation, self-organisation, skill development, resource reclamation, brain evolution, repertoires of daily routines, environmental management and defining health as the capacity to achieve one's valued goals illuminate occupation. The contexts in which people carry out their rounds of occupation also require study in order for occupational therapists to pose a ‘just right’ level of environmental challenge, enabling people to make an adaptive response in user-friendly environments. Recommended sources for new ideas are, first, self-reports of people who live with impairments and, second, literature from non-medical disciplines that share occupational therapy's holistic, integrated and optimistic view of people. The writings of people who live with chronic conditions reveal that they are not being served well by the current biomedical system. In contrast, scholarly detective work could foster occupational therapy that enhances satisfaction in daily living, influences health, reclaims resources and enables equality of capability for myriads of the world's populations. A keynote address, given on 8 September 1999 at the Inaugural United Kingdom Occupational Science Symposium, held at the College of Ripon and York St John, York.

NSF Outreach for Teachers and Students

The National Science Foundation is emerging as a major source of new ideas and materials, as well as financial support, for teachers throughout the educational system.

Evolution, development and complexity in Pere Alberch (1954–1998)

Evolution, development and complexity in Pere Alberch (1954–1998)