398 research outputs found
Recommended from our members
How Making it Easier to Succeed Reduces Success: IPO Reform and New Firm Performance
We examine how institutional changes that lower the barriers to successful exit influence the rate of IPO’s, the initial capitalization, and the performance of subsequent ventures. Such IPO market reforms are widespread, but their effectiveness is unclear. To do so, we take advantage of a quasi-natural experiment in which the IPO listing requirements in Japan were dramatically
reduced. Using a unique database of over 19,000 new firms incorporated after 1982, we find that IPO market reform is a powerful institutional lever that increases the rate of IPOs. But it is also a narrow instrument that influences only few industries and triggers poor average performance in those industries. Overall, we find that IPO market reform is a complex institutional change. We
conclude with contributions at the nexus institutional theory and entrepreneurship that indicate where and for whom institutional change will be effective
Methylome Alterations “Mark” New Therapeutic Opportunities in Glioblastoma
In this issue of Cancer Cell, Sturm et al. report that global DNA methylation patterns in glioblastoma multiforme divide adult and pediatric tumors into subgroups that have characteristic DNA mutations, mRNA profiles, and most importantly, different clinical behaviors. These findings suggest novel opportunities for therapeutics for this dreaded disease
Institutions and Maker Entrepreneurship
The nascent research on the maker movement highlights the implicit assumptions embedded in the literature on entrepreneurship and innovation based on a model of closed traditional product development. Instead, the maker culture emphasizes inclusiveness, openness, sharing, and collaboration. To date, we know little about how institutional-level factors (such as intellectual property rights protection, maker culture and access to makerspaces) impact the probability of a maker hobbyist becoming an entrepreneur. We leverage the institutional perspective to examine the differing regulatory, normative and cultural elements with a cross-national study. Thus, via a leading maker community, Hackster IO, we collected data from surveying 3,139 global makers from 99 countries during 2016, providing the first quantitative evidence about the maker movement's impact on firm creation. Our results suggest that having access to makerspaces positively correlates with the likelihood of being a maker entrepreneur. Intellectual property rights protection demonstrated an inverted-U shape relationship with being an entrepreneur. This paper provides the first large quantitative evidence on the wide existence of maker entrepreneurship across the world and how intuitional factors impact the creation of maker-founded firms in different societies
Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma
Abstract Background The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. Methods We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Results Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Conclusions Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes.http://deepblue.lib.umich.edu/bitstream/2027.42/78313/1/1471-2407-10-614.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78313/2/1471-2407-10-614.pdfPeer Reviewe
Identification of astrocytoma associated genes including cell surface markers
BACKGROUND: Despite intense effort the treatment options for the invasive astrocytic tumors are still limited to surgery and radiation therapy, with chemotherapy showing little or no increase in survival. The generation of Serial Analysis of Gene Expression (SAGE) profiles is expected to aid in the identification of astrocytoma-associated genes and highly expressed cell surface genes as molecular therapeutic targets. SAGE tag counts can be easily added to public expression databases and quickly disseminated to research efforts worldwide. METHODS: We generated and analyzed the SAGE transcription profiles of 25 primary grade II, III and IV astrocytomas [1]. These profiles were produced as part of the Cancer Genome Anatomy Project's SAGE Genie [2], and were used in an in silico search for candidate therapeutic targets by comparing astrocytoma to normal brain transcription. Real-time PCR and immunohistochemistry were used for the validation of selected candidate target genes in 2 independent sets of primary tumors. RESULTS: A restricted set of tumor-associated genes was identified for each grade that included genes not previously associated with astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase), with a high percentage of cell surface genes. Two genes with available antibodies, Aquaporin 1 and Topoisomerase 2A, showed protein expression consistent with transcript level predictions. CONCLUSIONS: This survey of transcription in malignant and normal brain tissues reveals a small subset of human genes that are activated in malignant astrocytomas. In addition to providing insights into pathway biology, we have revealed and quantified expression for a significant portion of cell surface and extra-cellular astrocytoma genes
Recommended from our members
Neoplastic cells are a rare component in human glioblastoma microvasculature
Microvascular proliferation is a key biological and diagnostic hallmark of human glioblastoma, one of the most aggressive forms of human cancer. It has recently been suggested that stem-like glioblastoma cells have the capacity to differentiate into functional endothelial cells, and that a significant proportion of the vascular lining in tumors has a neoplastic origin. In principle, this finding could significantly impact the efficacy and development of antiangiogenic therapies targeting the vasculature. While the potential of stem-like cancer cells to form endothelium in culture seems clear, in our clinical experience using a variety of molecular markers, neoplastic cells do not contribute significantly to the endothelial-lined vasculature of primary human glioblastoma. We sought to confirm this impression by analyzing vessels in glioblastoma previously examined using chromogenic in situ hybridization (CISH) for EGFR and immunohistochemistry for mutant IDH1. Vessels containing cells expressing these definitive neoplastic markers were identified in a small fraction of tumors, but only 10% of vessel profiles examined contained such cells and when identified these cells comprised less than 10% of the vascular cellularity in the cross section. Interestingly, these rare intravascular cells showing EGFR amplification by CISH or mutant IDH1 protein by immunohistochemistry were located in the middle or outer portions of vessel walls, but not amongst the morphologic boundaries of the endothelial lining. To more directly address the capacity of glioblastoma cells to contribute to the vascular endothelium, we performed double labeling (Immunofluorescence/FISH) for the endothelial marker CD34 and EGFR gene locus. Although rare CD34 positive neoplastic cells unassociated with vessels were identified (<1%), this analysis did not identify EGFR amplified cells within vascular linings, and further supports our observations that incorporation of glioblastoma cells into the tumor vessels is at best extremely rare, and therefore of questionable clinical or therapeutic significance
At Dawning (I Love You)
When the dawn flames in the sky I love you; When the birdlings wake and cry, I love you; When the swaying blades of corn Whisper soft at breaking morn, Love anew to me is born, I love you, I love you. Dawn and dew proclaim my dream, I love you; Chant the birds one thrilling theme, I love you; All the sounds of morning meet, Break in yearning at your feet. Come and answer, come, my sweet, I love you, I love you
At Dawning
[Verse 1] When the dawn flames in the sky, I love you; When the birdlings wake and cry, I love you; When the swaying blades of corn Whisper soft at breaking morn Love to me anew is born, I love you.
[Verse 2] Dawn and dew proclaim my dream, I love you; Chant the birds one thrilling theme, I love you; All the sounds of morning meet, Break in yearning at your feet, Come and answer, come, my sweet, I love you
Isolated endogenous Nocardia endophthalmitis after immunosuppression.
PURPOSE: This study is aimed to report a case of endogenous Nocardia endophthalmitis in the setting of immunosuppression from chronic steroid use.
METHODS: A case report was conducted.
RESULTS: A 79-year-old woman presented with decreased vision with floaters in the left eye. Ophthalmic examination revealed severe inflammation in the anterior chamber, vitreous opacities, and retinal detachment. Vitreous cultures grew Nocardia farcinica without any systemic foci of infection found during further workup. The patient was treated with intravitreal amikacin and oral trimethoprim-sulfamethoxazole, and her retinal detachment was later repaired in the operating room. The patient has since remained stable with no signs of retinal detachment or active infection.
CONCLUSIONS: Nocardia endophthalmitis is a rare, but serious intraocular infection that should be considered in the differential diagnosis in any immunosuppressed patient, including those receiving steroids, who presents with signs of intraocular infection
- …