Exploring the Problem-Finding and Problem-Solving Approach for Designing Organizations

An emerging problem-finding and problem-solving approach suggests that management's discovering problems to solve, opportunities to seize, and challenges to respond to, are vital to organizations. This paper explores the extent to which the problem-finding and problem-solving approach can provide a foundation for joining the capabilities, dynamic capabilities, and governance perspectives as a way to help scholars and practitioners to coherently design organizations from the perspective of design science. The problem-finding and problem-solving approach offers a unit of analysis and a set of behavioral assumptions that enable us to address open questions within the extant literature and to propose new questions in management research.

The utility of single nucleotide polymorphisms in inferences of population history

Single nucleotide polymorphisms (SNPs) represent the most widespread type of sequence variation in genomes, yet they have only emerged recently as valuable genetic markers for revealing the evolutionary history of populations. Their occurrence throughout the genome also makes them ideal for analyses of speciation and historical demography, especially in light of recent theory suggesting that many unlinked nuclear loci are needed to estimate population genetic parameters with statistical confidence. In spite of having lower variation compared with microsatellites, SNPs should make the comparison of genomic diversities and histories of different species (the core goal of comparative biogeography) more straightforward than has been possible with microsatellites. The most pervasive, but correctable, complication to SNP analysis is a bias towards analyzing only the most variable loci, an artifact that is usually introduced by the limited number of individuals used to screen initially for polymorphisms. Although the use of SNPs as markers in population studies is still new, innovative methods for SNP identification, automated screening, haplotype inference and statistical analysis might quickly make SNPs the marker of choice

Model of Genetic Variation in Human Social Networks

Social networks exhibit strikingly systematic patterns across a wide range of human contexts. While genetic variation accounts for a significant portion of the variation in many complex social behaviors, the heritability of egocentric social network attributes is unknown. Here we show that three of these attributes (in-degree, transitivity, and centrality) are heritable. We then develop a "mirror network" method to test extant network models and show that none accounts for observed genetic variation in human social networks. We propose an alternative "Attract and Introduce" model with two simple forms of heterogeneity that generates significant heritability as well as other important network features. We show that the model is well suited to real social networks in humans. These results suggest that natural selection may have played a role in the evolution of social networks. They also suggest that modeling intrinsic variation in network attributes may be important for understanding the way genes affect human behaviors and the way these behaviors spread from person to person.Comment: Additional materials related to the paper are available at http://jhfowler.ucsd.ed

AmpliTaq DNA polymerase, FS dye-terminator sequencing: Analysis of peak height patterns

Taq DNA polymerases in which the phenylalanine is substituted by a tyrosine at position 667 (Taq F667Y) are members of a new class of DNA polymerases that incorporate chain-terminating dideoxyribonucleoside triphosphates (ddNTPs) much more efficiently than the wild-type Taq DNA polymerase. Improved incorporation of ddNTPs into DNA during cycle sequencing using AmpliTaq DNA polymerase, FS (Taq-FS, a member of the Taq F667Y family), and dye-labeled primers results in nearly uniform peak heights in the sequencing trace. This is not the case when dye-labeled ddNTPs are used in Taq-FS cycle sequencing reactions. While the rate of dye-terminator incorporation is more efficient with Taq-FS, the peak pattern is still highly variable and different from that produced by the wild-type enzyme. We have systematically examined pairs of sequence-tagged sites that vary at only a single nucleotide to determine how base changes influence the peak heights of neighboring bases in sequencing traces generated by the Taq-FS dye-terminator chemistry. In 31 of 64 possible 3-base windows (48%), we find that the peak height of a particular base can be predicted by knowing just one or two bases 5\u27 to the base in question. We have also compared and contrasted the peak patterns produced by the Taq-FS enzyme with those previously identified for the wild-type enzyme. Establishing the patterns in peak heights within local sequence contexts can improve the accuracy of base-calling and the identification of polymorphisms/mutations when using the Taq-FS dye-terminator cycle-sequencing chemistry

The representation of scientific research in the national curriculum and secondary school pupils’ perceptions of research, its function, usefulness and value to their lives

Young people’s views on what research is, how it is conducted and whether it is important, influences the decisions they make about their further studies and career choices. In this paper we report the analysis of questionnaire data with a particular focus on pupil perceptions of research in the sciences and of the scientific method. The questionnaire was a 25-item Likert Scale (1-5) distributed to seven collaborating schools. We received 2634 returns from pupils across key stages 3, 4 and 5. We also asked teachers to complete the questionnaire in order to explore how they thought their pupils would respond. We received 54 teacher responses. Statistically significant differences in the responses were identified through a chi-square test on SPSS. As what is being taught influences secondary pupil views on research we also consider how the term ‘research’ appears in the national curriculum for England and Wales and the three main English exam boards. The main theoretical construct that informs our analysis of the questionnaire data and the national curriculum is Angela Brew’s 4-tier descriptor of perceptions of research (domino, trading, layer, journey). We use this framework in order to map what, when and how research is presented to school pupils in England and Wales. We also use this framework in order to highlight and discuss certain pupil views that emerged from the questionnaire data and which indicate areas where curriculum and pedagogy intervention may be necessary: pupils seem less confident in their understanding of research as involving the identification of a research question; and, they often see research as a means to confirm one’s own opinion. They do however understand research as involving the generation of new knowledge and the collection of new data, such as interviews and questionnaires as well as laboratory work, field trips and library searches and they appear relatively confident in their statements about their ability to do research, their school experiences of research and the importance of research in their future career choice

Casein kinase 2-mediated phosphorylation of Brahma-related gene 1 controls myoblast proliferation and contributes to SWI/SNF complex composition

Transcriptional regulation is modulated in part by chromatin-remodeling enzymes that control gene accessibility by altering chromatin compaction or nucleosome positioning. Brahma-related gene 1 (Brg1), a catalytic subunit of the mammalian SWI/SNF chromatin-remodeling enzymes, is required for both myoblast proliferation and differentiation, and the control of Brg1 phosphorylation by calcineurin, PKCbeta1, and p38 regulates the transition to differentiation. However, we hypothesized that Brg1 activity might be regulated by additional kinases. Here, we report that Brg1 is also a target of casein kinase 2 (CK2), a serine/threonine kinase, in proliferating myoblasts. We found that CK2 interacts with Brg1, and mutation of putative phosphorylation sites to non-phosphorylatable (Ser to Ala, SA) or phosphomimetic residues (Ser to Glu, SE) reduced Brg1 phosphorylation by CK2. Although BRG1-deleted myoblasts that ectopically express the SA-Brg1 mutant proliferated similarly to the parental cells or cells ectopically expressing wild-type (WT) Brg1, ectopic expression of the SE-Brg1 mutant reduced proliferation and increased cell death, similar to observations from cells lacking Brg1. Moreover, pharmacological inhibition of CK2 increased myoblast proliferation. Furthermore, the Pax7 promoter, which controls expression of a key transcription factor required for myoblast proliferation, was in an inaccessible chromatin state in the SE-Brg1 mutant, suggesting that hyperphosphorylated Brg1 cannot remodel chromatin. WT-, SA-, and SE-Brg1 exhibited distinct differences in interacting with and affecting expression of the SWI/SNF subunits Baf155 and Baf170 and displayed differential sub-nuclear localization. Our results indicate that CK2-mediated phosphorylation of Brg1 regulates myoblast proliferation and provides insight into one mechanism by which composition of the mammalian SWI/SNF enzyme complex is regulated

Algorithmic Complexity for Short Binary Strings Applied to Psychology: A Primer

Since human randomness production has been studied and widely used to assess executive functions (especially inhibition), many measures have been suggested to assess the degree to which a sequence is random-like. However, each of them focuses on one feature of randomness, leading authors to have to use multiple measures. Here we describe and advocate for the use of the accepted universal measure for randomness based on algorithmic complexity, by means of a novel previously presented technique using the the definition of algorithmic probability. A re-analysis of the classical Radio Zenith data in the light of the proposed measure and methodology is provided as a study case of an application.Comment: To appear in Behavior Research Method

Direct force probe reveals the mechanics of nuclear homeostasis in the mammalian cell

How cells maintain nuclear shape and position against various intracellular and extracellular forces is not well understood, although defects in nuclear mechanical homeostasis are associated with a variety of human diseases. We estimated the force required to displace and deform the nucleus in adherent living cells with a technique to locally pull the nuclear surface. A minimum pulling force of a few nanonewtons--far greater than typical intracellular motor forces--was required to significantly displace and deform the nucleus. Upon force removal, the original shape and position were restored quickly within a few seconds. This stiff, elastic response required the presence of vimentin, lamin A/C, and SUN (Sad1p, UNC-84)-domain protein linkages, but not F-actin or microtubules. Although F-actin and microtubules are known to exert mechanical forces on the nuclear surface through molecular motor activity, we conclude that the intermediate filament networks maintain nuclear mechanical homeostasis against localized forces