Management Factors Influencing Location Selection Decisions of Independent Filmmakers: An Exploratory Case Study

This is an exploratory case study of a management issue that confronts filmmakers: how do they select locations for their films? The outcome of those decisions can have vast and immediate effects upon the profitability of a film. This is a sometimes shadowy, but significant industry with a major economic impact. For systems theory advocates, students, and explorers, this study demonstrates that investigative, immersive action research techniques can be used to explore what are otherwise hidden, somewhat cloistered business organizations and industry structures that are ordinarily closed to outsiders. The soft-system of this industry that is rooted upon trust, loyalty, alliances, relationships, and other non-financial bonds influence its decisions, and its institutional performance. While this research is focused upon a fragment of the overall film industry worldwide, and is thus limited in the universality of the propositions that subsequently emerge, this study can serve as a springboard for research into other soft systems, from which new knowledge of managerial perspectives can emerge.     

Suggestions for New Application Areas for Soft Systems Methodology in the Information Age

Soft systems methodology (SSM) is now 40?years old. Another decade has passed since Checkland??s thirty year retrospective on the methodology, published in 2000. It can now be described as an old methodology. But it has adapted and changed over the years and is still very much alive, although the days are long gone when it was mainly developed and practised by its founders at the University of Lancaster. Interestingly, considering that many applications of SSM over the years have been to information systems, it was developed before the age of personal computers and the Internet. The way SSM is viewed has changed over the years as it has been applied to various types of problem situation. Every use of SSM will potentially hold methodological lessons in addition to those about the situation of concern; these may include SSMs framework of ideas, processes and way of use. How is SSM going to change in the future? This will depend in part on the types of problem situation to which it is applied. This paper examines some problem situations associated with emerging technologies in the information age to which SSM has not yet been much applied. These include computer simulation and virtual reality, ubiquitous computing and the design of cities, Information Technology Service Management and the design of enterprise information architectures. Some of the different worldviews associated with these problem situations which could be explored using SSM are noted.     

PTC124 targets genetic disorders caused by nonsense mutations

Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.     

Low beta diversity of herbivorous insects in tropical forests

Recent advances in understanding insect communities in tropical forests have contributed little to our knowledge of large-scale patterns of insect diversity, because incomplete taxonomic knowledge of many tropical species hinders the mapping of their distribution records. This impedes an understanding of global biodiversity patterns and explains why tropical insects are under-represented in conservation biology. Our study of approximately 500 species from three herbivorous guilds feeding on foliage (caterpillars, Lepidoptera), wood (ambrosia beetles, Coleoptera) and fruit (fruitflies, Diptera) found a low rate of change in species composition (beta diversity) across 75,000 square kilometres of contiguous lowland rainforest in Papua New Guinea, as most species were widely distributed. For caterpillars feeding on large plant genera, most species fed on multiple host species, so that even locally restricted plant species did not support endemic herbivores. Large plant genera represented a continuously distributed resource easily colonized by moths and butterflies over hundreds of kilometres. Low beta diversity was also documented in groups with differing host specificity (fruitflies and ambrosia beetles), suggesting that dispersal limitation does not have a substantial role in shaping the distribution of insect species in New Guinea lowland rainforests. Similar patterns of low beta diversity can be expected in other tropical lowland rainforests, as they are typically situated in the extensive low basins of major tropical rivers similar to the Sepik-Ramu region of New Guinea studied here.     

Structural definition of a conserved neutralization epitope on HIV-1 gp120

The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 A resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.     

Genome-wide detection and characterization of positive selection in human populations

With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.