The Prospects for Family Business in Research Universities

Family business shows the promise of becoming a respected scholarly field in research universities. However, success is not a given. We inquire about its prospects, with reference to the sociology of science. A key requirement for success that has been met is identification with an important and distinctive domain of inquiry. This domain is at the intersection two phenomena - of kinship and business - but more attention has been paid to enterprise than to kinship. We suggest that this creates important windows for theoretical development, an important requirement for a core presence in research universities. We further suggest additional priorities, such as progress in journal and research quality, more developed links to pressing social issues such as international business, inclusion of family business issues in the credit curriculum, and faculty lines that create research continuity and legitimize research on family business

Organizational Learning from Extreme Performance Experience: The Impact of Success and Recovery Experience

This paper argues that two different types of a firm’s own extreme performance experiences—success and recovery—and their interactions can generate survival-enhancing learning. Although these types of experience often represent valuable sources of useful learning, several important learning challenges arise when a firm has extremely limited prior experience of the same type. Thus, we theorize that a certain threshold of a given type of experience is required before each type of experience becomes valuable, with low levels of experience harming the organization. Furthermore, we propose that success and recovery experience will interact to enhance each other’s value. These conditions can help overcome learning challenges such as superstitious learning or learning from small samples. We investigate our ideas using a sample of the U.S. commercial banks founded between 1984 and 1998. Our results indicate that both success and recovery experience of a firm generate survival-enhancing learning, but only after a certain level of experience is reached. Furthermore, success and recovery experience enhance each other’s learning value, consistent with the theories that emphasize the importance of richer and contrasting experience in providing useful knowledge. Our framework advances organizational learning theory by presenting a contingent model of the impact of success and recovery experience and their interaction

Myopia during emergency improvisation: lessons from a catastrophic wildfire

Purpose The purpose of this paper is to explore how a number of processes joined to create the microlevel strategies and procedures that resulted in the most lethal and tragic forest fire in Portugal's history, recalled as the EN236-1 road tragedy in the fire of Pedrogao Grande. Design/methodology/approach Using an inductive theory development approach, the authors consider how the urgency and scale of perceived danger coupled with failures of system-wide communication led fire teams to improvise repeatedly. Findings The paper shows how structure collapse led teams to use only local information prompting acts of improvisational myopia, in the particular shape of corrosive myopia, and how a form of incidental improvisation led to catastrophic results. Practical implications The research offers insights into the dangers of improvisation arising from corrosive myopia, identifying ways to minimize them with the development of improvisation practices that allow for the creation of new patterns of action. The implications for managing surprise through improvisation extend to risk contexts beyond wildfires. Originality/value The paper stands out for showing the impact of improvisational myopia, especially in its corrosive form, which stands in stark contrast to the central role of attention to the local context highlighted in previous research on improvisation. At the same time, by exploring the effects of incidental improvisation, it also departs from the agentic conception of improvisation widely discussed in the improvisation literature.info:eu-repo/semantics/acceptedVersio

Spillback Effects of Expansion When Product-Types and Firm-Types Differ

Contrary to perspectives that credit firms with only limited abilities to undertake significant change successfully, recent research has demonstrated that firms often improve their performance after undertaking major expansion to their operations. In this paper, we build on a study by Mitchell and Singh (1993) to test for differences in expansion effects, depending on whether the new goods substitute for old products and whether the firm is a generalist or specialist participant in the industry. The analysis helps us understand when a business can undertake major change successfully. The results have implications for ecological and other definitions of the core of a business and highlight the necessity for firms to undertake changes even at considerable risk to their existing operations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68398/2/10.1177_014920639502100105.pd

Abnormal Wnt and PI3Kinase Signaling in the Malformed Intestine of lama5 Deficient Mice

Laminins are major constituents of basement membranes and are essential for tissue homeostasis. Laminin-511 is highly expressed in the intestine and its absence causes severe malformation of the intestine and embryonic lethality. To understand the mechanistic role of laminin-511 in tissue homeostasis, we used RNA profiling of embryonic intestinal tissue of lama5 knockout mice and identified a lama5 specific gene expression signature. By combining cell culture experiments with mediated knockdown approaches, we provide a mechanistic link between laminin α5 gene deficiency and the physiological phenotype. We show that laminin α5 plays a crucial role in both epithelial and mesenchymal cell behavior by inhibiting Wnt and activating PI3K signaling. We conclude that conflicting signals are elicited in the absence of lama5, which alter cell adhesion, migration as well as epithelial and muscle differentiation. Conversely, adhesion to laminin-511 may serve as a potent regulator of known interconnected PI3K/Akt and Wnt signaling pathways. Thus deregulated adhesion to laminin-511 may be instrumental in diseases such as human pathologies of the gut where laminin-511 is abnormally expressed as it is shown here

Efficacy and tolerability of folate-aminopterin therapy in a rat focal model of multiple sclerosis

BackgroundActivated macrophages in the experimental model of multiple sclerosis (MS) express folate receptor-beta (FR-beta), representing a promising target for the treatment of MS. Here, we both evaluated the efficacy of a novel folate-aminopterin construct (EC2319) in a rat focal model of multiple sclerosis (MS) and investigated the utility of Ga-68-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated folate (Ga-68-FOL) for assessing inflammatory lesions. In addition, we investigated whether FR-beta is expressed in the brain of patients with MS.MethodsFocal delayed-type hypersensitivity experimental autoimmune encephalomyelitis (fDTH-EAE) was induced in 40 Lewis rats; 20 healthy Lewis rats were used as controls. Rats were divided into six groups according to the duration of disease (control, acute, or chronic) and intervention (vehicle versus EC2319). Ga-68-FOL analyses, histology, and immunofluorescence of the brain were performed to evaluate the efficacy of subcutaneously administered EC2319 on lesion development. Immunofluorescence was used to assess FR-beta expression in postmortem brain samples from 5 patients with MS and 5 healthy controls.ResultsImmunofluorescence and histological analyses revealed significant reductions in FR-beta expression (P < 0.05) and lesion size (P < 0.01), as well as improved inducible nitric oxide synthase/mannose receptor C type 1 ratios (P < 0.01) in macrophages and microglia during the chronic but not acute phase of fDTH-EAE in EC2319-treated rats. The uptake of IV-injected Ga-68-FOL in the brain was low and did not differ between the groups, but the in vitro binding of Ga-68-FOL was significantly lower in EC2319-treated rats (P < 0.01). FR-beta positivity was observed in chronically active lesions and in normal-appearing white matter in MS brain samples.ConclusionsEC2319 was well tolerated and attenuated inflammation and lesion development in a rat model of a chronic progressive form of MS. Human MS patients have FR-beta -positive cells in chronically active plaques, which suggests that these results may have translational relevance

Understanding hereditary diseases using the dog and human as companion model systems

Animal models are requisite for genetic dissection of, and improved treatment regimens for, human hereditary diseases. While several animals have been used in academic and industrial research, the primary model for dissection of hereditary diseases has been the many strains of the laboratory mouse. However, given its greater (than the mouse) genetic similarity to the human, high number of naturally occurring hereditary diseases, unique population structure, and the availability of the complete genome sequence, the purebred dog has emerged as a powerful model for study of diseases. The major advantage the dog provides is that it is afflicted with approximately 450 hereditary diseases, about half of which have remarkable clinical similarities to corresponding diseases of the human. In addition, humankind has a strong desire to cure diseases of the dog so these two facts make the dog an ideal clinical and genetic model. This review highlights several of these shared hereditary diseases. Specifically, the canine models discussed herein have played important roles in identification of causative genes and/or have been utilized in novel therapeutic approaches of interest to the dog and human

A Genome-Wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci

A genome-wide association study was performed to identify genetic factors involved in susceptibility to psoriasis (PS) and psoriatic arthritis (PSA), inflammatory diseases of the skin and joints in humans. 223 PS cases (including 91 with PSA) were genotyped with 311,398 single nucleotide polymorphisms (SNPs), and results were compared with those from 519 Northern European controls. Replications were performed with an independent cohort of 577 PS cases and 737 controls from the U.S., and 576 PSA patients and 480 controls from the U.K.. Strongest associations were with the class I region of the major histocompatibility complex (MHC). The most highly associated SNP was rs10484554, which lies 34.7 kb upstream from HLA-C (P = 7.8×10−11, GWA scan; P = 1.8×10−30, replication; P = 1.8×10−39, combined; U.K. PSA: P = 6.9×10−11). However, rs2395029 encoding the G2V polymorphism within the class I gene HCP5 (combined P = 2.13×10−26 in U.S. cases) yielded the highest ORs with both PS and PSA (4.1 and 3.2 respectively). This variant is associated with low viral set point following HIV infection and its effect is independent of rs10484554. We replicated the previously reported association with interleukin 23 receptor and interleukin 12B (IL12B) polymorphisms in PS and PSA cohorts (IL23R: rs11209026, U.S. PS, P = 1.4×10−4; U.K. PSA: P = 8.0×10−4; IL12B:rs6887695, U.S. PS, P = 5×10−5 and U.K. PSA, P = 1.3×10−3) and detected an independent association in the IL23R region with a SNP 4 kb upstream from IL12RB2 (P = 0.001). Novel associations replicated in the U.S. PS cohort included the region harboring lipoma HMGIC fusion partner (LHFP) and conserved oligomeric golgi complex component 6 (COG6) genes on chromosome 13q13 (combined P = 2×10−6 for rs7993214; OR = 0.71), the late cornified envelope gene cluster (LCE) from the Epidermal Differentiation Complex (PSORS4) (combined P = 6.2×10−5 for rs6701216; OR 1.45) and a region of LD at 15q21 (combined P = 2.9×10−5 for rs3803369; OR = 1.43). This region is of interest because it harbors ubiquitin-specific protease-8 whose processed pseudogene lies upstream from HLA-C. This region of 15q21 also harbors the gene for SPPL2A (signal peptide peptidase like 2a) which activates tumor necrosis factor alpha by cleavage, triggering the expression of IL12 in human dendritic cells. We also identified a novel PSA (and potentially PS) locus on chromosome 4q27. This region harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and was recently shown to be associated with four autoimmune diseases (Celiac disease, Type 1 diabetes, Grave's disease and Rheumatoid Arthritis)

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead