77 research outputs found

    From start-up to acquisition: Implications of financial investment trends for small- to medium-sized high-tech enterprises

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    The high-technology (high-tech) industry is a dynamic environment defined by both frequent changes in composition and a concentration of market power through consolidation. Operating as a new or small venture within this environment poses many complex challenges, especially when considering the financial resources needed to be successful. In their efforts to obtain financial resources, entrepreneurs often overlook how the choice and pattern of investment funding to maintain a growth path can later affect a successful entrepreneurial exit. Exit via acquisition for small- to medium-sized technology enterprises (SMTEs) is a strong area of interest given firms in the U.S. high-tech industry experience the fastest growth rates and have been the target of over $400 billion in deal volume and 20% of all merger and acquisition (M&A) transactions in the last twenty years. Much of this M&A activity is conducted by five prominent firms, Alphabet, Amazon, Apple, Facebook, Microsoft, commonly referred to as the Fearsome Five or the ā€œFANGSā€. However, as there has been only limited research examining this unique M&A context, in this study we explore the investment funding factors influencing exit via acquisition by the Fearsome Five. We highlight questions and potential concerns for SMTEs given the trends in financial investments and increasing market power

    Metalloproteinase expression in venous aneurysms

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    IntroductionAlthough recognized with increasing frequency, the pathogenesis of venous aneurysms (VA) remains poorly understood. We evaluated 8 patients with 10 VA for the presence, localization and activity of metalloproteinases (MMPs).MethodsTissue specimens from VA (n=8), normal saphenous vein (NSV n=7) and varicose veins (VV n=7 were compared by histology and immunohistochemistry (IHC). Histologic sections were stained with H&E, Movats pentachrome and toluidine blue, and IHC specimens with antibodies to CD68, MMP2, MMP9, and MMP13. Protein expression and enzyme activity were determined by Western immunoblotting and zymography.ResultsThree of 4 patients with popliteal VA presented with edema and leg pain and the remaining patient with deep venous thrombosis (DVT) and pulmonary embolism (PE). The 5 popliteal VA were treated by; excision and reanastomosis (n=2) lateral venorrhaphy (n=2) and spiral saphenous vein graft (n=1). The 3 patients with 4 upper extremity VA had discomfort over a compressible mass. Two of the VA were excised and the remaining patients aneurysm ruptured spontaneously. The mesenteric VA, an incidental finding at laparotomy was excised. Thrombus was present in 2 popliteal, 1 upper extremity and in the mesenteric aneurysm. Histologically, VA and VV were characterized by fragmentation of the elastic lamellae, loss of smooth muscle cells (SMCs) and attenuation of the venous wall when compared to NSV. Varicose veins and VA also demonstrated increased expression of MMP-2, MMP-9 and MMP-13 in endothelial cells (ECs), SMCs and adventitial microvessels compared to NSV. Both pro-MMP-2 and pro-MMP-9 were detected by zymography in VA,VV and NSV but only MMP-2 activity was demonstrable.ConclusionsThe structural changes in the venous wall in addition to the increased expression of MMP-2, MMP-9 and MMP-13 in VA compared to NSV and VV suggests a possible causal role for these MMPs in their pathogenesis

    Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies

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    To study the substrate specificity of enzymes, we use the amidohydrolase and enolase superfamilies as model systems; members of these superfamilies share a common TIM barrel fold and catalyze a wide range of chemical reactions. Here, we describe a collaboration between the Enzyme Specificity Consortium (ENSPEC) and the New York SGX Research Center for Structural Genomics (NYSGXRC) that aims to maximize the structural coverage of the amidohydrolase and enolase superfamilies. Using sequence- and structure-based protein comparisons, we first selected 535 target proteins from a variety of genomes for high-throughput structure determination by X-ray crystallography; 63 of these targets were not previously annotated as superfamily members. To date, 20 unique amidohydrolase and 41 unique enolase structures have been determined, increasing the fraction of sequences in the two superfamilies that can be modeled based on at least 30% sequence identity from 45% to 73%. We present case studies of proteins related to uronate isomerase (an amidohydrolase superfamily member) and mandelate racemase (an enolase superfamily member), to illustrate how this structure-focused approach can be used to generate hypotheses about sequenceā€“structureā€“function relationships
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