The time-dependent localization of Ki 67 antigen-positive cells in human skin wounds

A total of 77 human skin wounds with a post-infliction interval between 3 h and 7 months were investigated and the proliferation marker antigen Ki 67 was visualized in paraffin sections using a specific monoclonal antibody (MIB). The re-built epidermal layer covering the former lesional area showed only a few basal cells positively staining for Ki 67 antigen. No enhanced reactivity was found when compared to uninjured skin. In basal cells of the epidermis adjacent to the wound area, however, varying numbers of positive cells occurred, but no information useful for a reliable time estimation of skin wounds could be obtained due to the considerable variability in the number of Ki 67 positive epidermal basal cells found in non-damaged skin. Fibroblastic cells in the wound area revealed an increased number of Ki 67-positive sites which could first be detected in a 1.5-day-old skin lesion. Positive results could be obtained in every specimen investigated after a post-infliction interval of 6 days up to 1.5 months. Only the scar tissue of the oldest wound examined (wound age 7 months) revealed no increase in the number of positively staining fibroblasts. Therefore, positive results indicate a wound age of at least approximately 1.5 days and the lack of an increased number of positive fibroblastic cells in a sufficient number of specimens indicates at a wound age of less than 6 days, but cannot totally exclude longer post-infliction intervals

How the country context shapes firms' competitive repertoire complexity

Research Summary: Recent research has shown that firms' ability to employ complex competitive repertoires can create long-term competitive advantages. Since research on its determinants has focused on the firm level, we lack an understanding of how country-level factors impact firms' implementation of complex competitive repertoires. Our cross-country study addresses this gap by integrating a model of country-level competitiveness factors with insights from the literature on competitive dynamics and portable governance. We argue that a country context with high-quality competitiveness factors enables firms to implement complex competitive repertoires. In addition, we hypothesize that firms with foreign investors from countries with high-quality competitiveness factors can partially compensate for low-quality factors in firms' domestic context. We found support for our hypotheses in an unbalanced sample containing 1,340 firms from 32 countries. Managerial Summary: Employing complex competitive repertoires (i.e., diverse and dynamic arrays of competitive actions), such as price reductions or new product introductions, can help firms outcompete their competition. We argue and empirically show that firms' domestic country context, specifically high-quality governance, factor and demand conditions, related and supporting industries, and strong context for rivalry drive their ability to implement complex repertoires. Moreover, we find that ownership by foreign investors from favorable country backgrounds can partly compensate for firms' weak conditions at home by serving as enabling bridges. Managers who aim to improve their firms' repertoire complexity but are restricted by their domestic country context may consider attracting foreign investors from countries that have what their countries lack

Determinants of common ownership:Exploring an information-based and a competition-based perspective in a global context

This study explores the determinants of common ownership. Drawing on two explanatory lenses, we suggest an information-based perspective and a competition-based perspective. We theorize on and empirically test both perspectives at the firm, industry, and country levels. Based on 14,372 observations of firms from the MSCI All Country World Index for the years 2008 to 2017, we find evidence supporting the information-based perspective at the firm, industry, and country levels: Access to and the value of private information about rival firms increases common ownership. For the competition-based perspective, we find support at the industry and country levels, specifically uncovering that common ownership is higher in more concentrated industries and in countries with more extensive laws regarding anticompetitive conduct. Our findings contribute to research by stressing the relevance of both perspectives. Overall, our study has broader implications for understanding the emerging phenomenon of common ownership

eTRIKS Analytical Environment: A Modular High Performance Framework for Medical Data Analysis

Translational research is quickly becoming a science driven by big data. Improving patient care, developing personalized therapies and new drugs depend increasingly on an organization's ability to rapidly and intelligently leverage complex molecular and clinical data from a variety of large-scale partner and public sources. As analysing these large-scale datasets becomes computationally increasingly expensive, traditional analytical engines are struggling to provide a timely answer to the questions that biomedical scientists are asking. Designing such a framework is developing for a moving target as the very nature of biomedical research based on big data requires an environment capable of adapting quickly and efficiently in response to evolving questions. The resulting framework consequently must be scalable in face of large amounts of data, flexible, efficient and resilient to failure. In this paper we design the eTRIKS Analytical Environment (eAE), a scalable and modular framework for the efficient management and analysis of large scale medical data, in particular the massive amounts of data produced by high-throughput technologies. We particularly discuss how we design the eAE as a modular and efficient framework enabling us to add new components or replace old ones easily. We further elaborate on its use for a set of challenging big data use cases in medicine and drug discovery

Immunohistochemical localization of fibronectin as a tool for the age determination of human skin wounds

We analyzed the distribution of fibronectin in routinely embedded tissue specimens from 53 skin wounds and 6 postmortem wounds. In postmortem wounds a faint but focal positive staining was exclusively found at the margin of the specimens which dit not extend into the adjacent stroma. Vital wounds were classified into 3 groups. The first comprising lesions with wound ages ranging from a few seconds to 30 min, the second comprising those with wound ages upt to 3 weeks, and the third group with lesions more than 3 weeks old. Ten out of 17 lesions with a wound age up to 30 min showed a clear positive reaction within the wound area. Three specimens in this group were completely negative, while in 4 additional cases the result was not significantly different from postmortem lesions. These 7 cases were characterized by acute death with extremely short survival times (only seconds). In wounds up to 3 weeks old fibronectin formed a distinct network containing an increasing number of inflammatory cells corresponding to the wound age. In 2 cases with a survival time of 17 days and in all wounds older than 3 weeks fibronectin was restricted to the surface of fibroblasts and to parallel arranged fibers in the granulation tissue without any network structures. We present evidence that fibronectin is a useful marker for vital wounds with a survival time of more than a few minutes. Fibronectin appears before neutrophilic granulocytes migrate into the wound area. Since a faint positive fibronectin staining is seen in postmortem lesions and bleedings, we propose that only those wounds which show strong positive fibronectin staining also extending into the adjacent stroma should be regarded as vital

Galaxy Zoo: Kinematics of strongly and weakly barred galaxies

We study the bar pattern speeds and corotation radii of 225 barred galaxies, using IFU data from MaNGA and the Tremaine-Weinberg method. Our sample, which is divided between strongly and weakly barred galaxies identified via Galaxy Zoo, is the largest that this method has been applied to. We find lower pattern speeds for strongly barred galaxies than for weakly barred galaxies. As simulations show that the pattern speed decreases as the bar exchanges angular momentum with its host, these results suggest that strong bars are more evolved than weak bars. Interestingly, the corotation radius is not different between weakly and strongly barred galaxies, despite being proportional to bar length. We also find that the corotation radius is significantly different between quenching and star forming galaxies. Additionally, we find that strongly barred galaxies have significantly lower values for R, the ratio between the corotation radius and the bar radius, than weakly barred galaxies, despite a big overlap in both distributions. This ratio classifies bars into ultrafast bars (R < 1.0; 11% of our sample), fast bars (1.0 < R < 1.4; 27%) and slow bars (R > 1.4; 62%). Simulations show that R is correlated with the bar formation mechanism, so our results suggest that strong bars are more likely to be formed by different mechanisms than weak bars. Finally, we find a lower fraction of ultrafast bars than most other studies, which decreases the recently claimed tension with {\Lambda}CDM. However, the median value of R is still lower than what is predicted by simulations.Comment: 20 pages, 16 figure

An experimental protocol for mimicking pathomechanisms of traumatic brain injury in mice

Traumatic brain injury (TBI) is a result of an outside force causing immediate mechanical disruption of brain tissue and delayed pathogenic events. In order to examine injury processes associated with TBI, a number of rodent models to induce brain trauma have been described. However, none of these models covers the entire spectrum of events that might occur in TBI. Here we provide a thorough methodological description of a straightforward closed head weight drop mouse model to assess brain injuries close to the clinical conditions of human TBI

Inner ear hair cells produced in vitro by a mesenchymal-to-epithelial transition

Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of National academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 104 (2007): 16675-16680, doi:10.1073/pnas.0704576104.Sensory hair cell loss is a major contributor to disabling hearing and balance deficits that affect >250 million people worldwide. Sound exposures, infections, drug toxicity, genetic disorders, and aging all can cause hair cell loss and lead to permanent sensory deficits. Progress toward treatments for these deficits has been limited, in part because hair cells have only been obtainable via microdissection of the anatomically complex internal ear. Attempts to produce hair cells in vitro have resulted in reports of some success, but have required transplantation into embryonic ears or co-culturing with other tissues. Here we show that avian inner ear cells can be cultured and passaged for months, frozen, and expanded to large numbers without other tissues. At any point from passage 6 up to at least passage 23, these cultures can be fully dissociated and then aggregated in suspension to induce a mesenchymal-to-epithelial transition that reliably yields new polarized sensory epithelia. Those epithelia develop numerous hair cells that are crowned by hair bundles, comprised of a single kinocilium and an asymmetric array of stereocilia. These hair cells exhibit rapid permeance to FM1-43, a dye that passes through open mechanotransducing channels. Since a vial of frozen cells can now provide the capacity to produce bona fide hair cells completely in vitro, these discoveries should open new avenues of research that may ultimately contribute to better treatments for hearing loss and other inner ear disorders.Supported by NIH grants DC00200 and DC006182to J.T.C