Universities And Business: Partnering for the Knowledge Society

Preface by Luc E. Weber and James J. Duderstadt Contributors and participants PART I: THE ROLE OF UNIVERSITIES, BUSINESS AND GOVERNMENT IN MEETING THE NEEDS OF SOCIETY Chapter 1, European Strategy to promote the Knowledge Society as a Source of renewed economic Dynamism and of social Cohesion Luc E. WEBER Chapter 2, University-Industry-Government Partnerships for a 21st century Global, Knowledge-Driven Economy: An American Perspective James J. DUDERSTADT Chapter 3, War and peace: how did we get here in HE-business relations? Alice FOSTER and Howard NEWBY Chapter 4, Strategic Alliances between Universities and their Communities Brenda M. GOURLEY and John L. BRENNAN Chapter 5, Higher Education Systems Dynamics and Useful Knowledge Creation Frans van VUGHT PART II: KNOWLEDGE TRANSFER Chapter 6, European Research Policy: Towards Knowledge and Innovation or Trivial Pursuit Bertil ANDERSSON Chapter 7, Knowledge Diffusion: The Prospects for More Productive University-Industry Partnerships Anita JONES Chapter 8, The Collaboration Imperative Wayne C. JOHNSON Chapter 9, Global Networks and Knowledge Diffusion: the Quantum physics model of the 21st century University William R. BRODY Chapter 10, Innovation and wealth creation Dennis TSICHRITZIS and Michael-Alexander KREYSEL PART III: THE EUROPEAN EXPERIENCE Chapter 11, The EPFL approach to Innovation Hervé LEBRET, Jan-Anders MANSON and Patrick AEBISCHER Chapter 12, Developing ongoing Research and Learning Relationships between Business Firms and Academic Institutions Sigvald HARRYSON and Peter LORANGE Chapter 13, Best Practice in Business-University Collaboration Richard LAMBERT Chapter 14, Obstacles to University–Industry Relations Horst SOBOLL Chapter 15, University-Industry Collaborations: a Source of Continuous Mutual Stimulation and Inspiration Klaus MUELLER PART IV: THE AMERICAN EXPERIENCE Chapter 16, Universities, Businesses and Public Authorities — the Inclusive Development of Society Marye Anne FOX Chapter 17, Lessons about Regional Economic Development from the Austin Story Larry FAULKNER Chapter 18, Challenges in University-Industry Collaborations Wayne C. JOHNSON Chapter 19, Effective Knowledge Transfer: from Research Universities to Industry Thomas CONNELLY PART V: HUMAN CAPITAL Chapter 20, Declining Demand among Students for Science and Engineering? Georg WINCKLER and Martin FIEDER Chapter 21, Declining Interest in Engineering Studies at a Time of Increased Business Need Wayne C. JOHNSON and Russel C. JONES Chapter 22, A Mosaic of Problems Wm. A. WULF Chapter 23, Best Practices in Knowledge Transfer Charles M. VEST PART VI: SUMMARY Chapter 24, Universities and business — a view from a food company Peter BRABECK-LETMATHE Chapter 25, University-Business Partnership for a Knowledge Society James J. DUDERSADT and Luc E. WEBERGlion Colloquiumhttp://deepblue.lib.umich.edu/bitstream/2027.42/57289/1/jjd_Universities And Business Partnering for the Knowledge Society.pd

Four quasars above redshift 6 discovered by the Canada-France High-z Quasar Survey

The Canada-France High-z Quasar Survey (CFHQS) is an optical survey designed to locate quasars during the epoch of reionization. In this paper we present the discovery of the first four CFHQS quasars at redshift greater than 6, including the most distant known quasar, CFHQS J2329-0301 at z=6.43. We describe the observational method used to identify the quasars and present optical, infrared, and millimeter photometry and optical and near-infrared spectroscopy. We investigate the dust properties of these quasars finding an unusual dust extinction curve for one quasar and a high far-infrared luminosity due to dust emission for another. The mean millimeter continuum flux for CFHQS quasars is substantially lower than that for SDSS quasars at the same redshift, likely due to a correlation with quasar UV luminosity. For two quasars with sufficiently high signal-to-noise optical spectra, we use the spectra to investigate the ionization state of hydrogen at z>5. For CFHQS J1509-1749 at z=6.12, we find significant evolution (beyond a simple extrapolation of lower redshift data) in the Gunn-Peterson optical depth at z>5.4. The line-of-sight to this quasar has one of the highest known optical depths at z~5.8. An analysis of the sizes of the highly-ionized near-zones in the spectra of two quasars at z=6.12 and z=6.43 suggest the IGM surrounding these quasars was substantially ionized before these quasars turned on. Together, these observations point towards an extended reionization process, but we caution that cosmic variance is still a major limitation in z>6 quasar observations.Comment: 15 pages, 9 figures, AJ, in press, minor changes to previous versio

First Steps Towards an Understanding of a Mode ofCarcinogenic Action for Vanadium Pentoxide

Inhalation of vanadium pentoxide clearly increases the incidence of alveolar/bronchiolar neoplasms in male and female B6C3F1 mice at all concentrations tested (1, 2 or 4 mg/m3), whereas responses in F344/N rats was, at most, ambiguous. While vanadium pentoxide is mutagenic in vitro and possibly in vivo in mice, this does not explain the species or site specificity of the neoplastic response. A nose-only inhalation study was conducted in female B6C3F1 mice (0, 0.25, 1 and 4 mg/m3, 6 h/day for 16 days) to explore histopathological, biochemical (α-tocopherol, glutathione and F2-isoprostane) and genetic (comet assays and 9 specific DNA-oxo-adducts) changes in the lungs. No treatment related histopathology was observed at 0.25 mg/m3. At 1 and 4 mg/m3, exposure-dependent increases were observed in lung weight, alveolar histiocytosis, sub-acute alveolitis and/or granulocytic infiltration and a generally time-dependent increased cell proliferation rate of histiocytes. Glutathione was slightly increased, whereas there were no consistent changes in α-tocopherol or 8-isoprostane F2α. There was no evidence for DNA strand breakage in lung or BAL cells, but there was an increase in 8-oxodGuo DNA lesions that could have been due to vanadium pentoxide induction of the lesions or inhibition of repair of spontaneous lesions. Thus, earlier reports of histopathological changes in the lungs after inhalation of vanadium pentoxide were confirmed, but no evidence has yet emerged for a genotoxic mode of action. Evidence is weak for oxidative stress playing any role in lung carcinogenesis at the lowest effective concentrations of vanadium pentoxide

The vascular gene Apold1 is dispensable for normal development but controls angiogenesis under pathological conditions

The molecular mechanisms of angiogenesis have been intensely studied, but many genes that control endothelial behavior and fate still need to be described. Here, we characterize the role of Apold1 (Apolipoprotein L domain containing 1) in angiogenesis in vivo and in vitro. Single-cell analyses reveal that - across tissues - the expression of Apold1 is restricted to the vasculature and that Apold1 expression in endothelial cells (ECs) is highly sensitive to environmental factors. Using Apold1$^{-/-}$ mice, we find that Apold1 is dispensable for development and does not affect postnatal retinal angiogenesis nor alters the vascular network in adult brain and muscle. However, when exposed to ischemic conditions following photothrombotic stroke as well as femoral artery ligation, Apold1$^{-/-}$ mice display dramatic impairments in recovery and revascularization. We also find that human tumor endothelial cells express strikingly higher levels of Apold1 and that Apold1 deletion in mice stunts the growth of subcutaneous B16 melanoma tumors, which have smaller and poorly perfused vessels. Mechanistically, Apold1 is activated in ECs upon growth factor stimulation as well as in hypoxia, and Apold1 intrinsically controls EC proliferation but not migration. Our data demonstrate that Apold1 is a key regulator of angiogenesis in pathological settings, whereas it does not affect developmental angiogenesis, thus making it a promising candidate for clinical investigation

The Infrared Imaging Spectrograph (IRIS) for TMT: instrument overview

IRIS is a near-infrared (0.84 to 2.4 micron) integral field spectrograph and wide-field imager being developed for first light with the Thirty Meter Telescope (TMT). It mounts to the advanced adaptive optics (AO) system NFIRAOS and has integrated on-instrument wavefront sensors (OIWFS) to achieve diffraction-limited spatial resolution at wavelengths longer than 1 μm. With moderate spectral resolution (R ~ 4000 – 8,000) and large bandpass over a continuous field of view, IRIS will open new opportunities in virtually every area of astrophysical science. It will be able to resolve surface features tens of kilometers across Titan, while also mapping the most distant galaxies at the scale of an individual star forming region. This paper summarizes the entire design and capabilities, and includes the results from the nearly completed preliminary design phase

Globin-like proteins in Caenorhabditis elegans: in vivo localization, ligand binding and structural properties

Background: The genome of the nematode Caenorhabditis elegans contains more than 30 putative globin genes that all are transcribed. Although their translated amino acid sequences fit the globin fold, a variety of amino-acid substitutions and extensions generate a wide structural diversity among the putative globins. No information is available on the physicochemical properties and the in vivo expression. Results: We expressed the globins in a bacterial system, characterized the purified proteins by optical and resonance Raman spectroscopy, measured the kinetics and equilibria of O2 binding and determined the crystal structure of GLB-1* (CysGH2 T Ser mutant). Furthermore, we studied the expression patterns of glb-1 (ZK637.13) and glb-26 (T22C1.2) in the worms using green fluorescent protein technology and measured alterations of their transcript abundances under hypoxic conditions.GLB-1* displays the classical three-over-three α-helical sandwich of vertebrate globins, assembled in a homodimer associated through facing E- and F-helices. Within the heme pocket the dioxygen molecule is stabilized by a hydrogen bonded network including TyrB10 and GlnE7.GLB-1 exhibits high ligand affinity, which is, however, lower than in other globins with the same distal TyrB10-GlnE7 amino-acid pair. In the absence of external ligands, the heme ferrous iron of GLB-26 is strongly hexacoordinated with HisE7, which could explain its extremely low affinity for CO. This globin oxidizes instantly to the ferric form in the presence of oxygen and is therefore incapable of reversible oxygen binding. Conclusion: The presented data indicate that GLB-1 and GLB-26 belong to two functionally-different globin classes

Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that the toll-like receptor 3 (TLR3) is an interesting target for anti-cancer therapy. Unfortunately, most laboratory investigations about the impact of TLR3 stimulation on human malignant cells have been performed with very high concentrations - 5 to 100 μg/ml - of the prototype TLR3 ligand, poly(I:C). In a previous study focused on a specific type of human carcinoma - nasopharyngeal carcinoma - we have shown that concentrations of poly(I:C) as low as 100 ng/ml are sufficient to induce apoptosis of malignant cells when combined to a pharmacological antagonist of the IAP family based on Smac mimicry.</p> <p>Methods</p> <p>This observation prompted us to investigate the contribution of the IAP family in cell response to poly(I:C) in a variety of human malignant cell types.</p> <p>Results</p> <p>We report a rapid, intense and selective increase in c-IAP2 protein expression observed under stimulation by poly(I:C)(500 ng/ml) in all types of human malignant cells. In most cell types, this change in protein expression is underlain by an increase in c-IAP2 transcripts and dependent on the TLR3/TRIF pathway. When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines.</p> <p>Conclusions</p> <p>Currently, IAP inhibitors like RMT 5265 and poly(I:C) are the subject of separate therapeutic trials. In light of our observations, combined use of both types of compounds should be considered for treatment of human malignancies including carcinomas and melanomas.</p

As the Walls of Academia are Tumbling Down

http://deepblue.lib.umich.edu/bitstream/2027.42/58008/1/2717844392.pd

Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin

Single nucleotide polymorphisms (SNPs) in the multiple drug resistance protein 1 (MRP1) and P-glycoprotein 1 (MDR1) genes modulate their ability to mediate drug resistance. We therefore sought to retrospectively evaluate their influence on outcomes in relapsed and/or refractory myeloma patients treated with bortezomib or bortezomib with pegylated liposomal doxorubicin (PLD). The MRP1/R723Q polymorphism was found in five subjects among the 279 patient study population, all of whom received PLD + bortezomib. Its presence was associated with a longer time to progression (TTP; median 330 vs. 129 days; p = 0.0008), progression-free survival (PFS; median 338 vs. 129 days; p = 0.0006), and overall survival (p = 0.0045). MDR1/3435(C > T), which was in Hardy–Weinberg equilibrium, showed a trend of association with PFS (p = 0.0578), response rate (p = 0.0782) and TTP (p = 0.0923) in PLD + bortezomib patients, though no correlation was found in the bortezomib arm. In a recessive genetic model, MDR1/3435 T was significantly associated with a better TTP (p = 0.0405) and PFS (p = 0.0186) in PLD + bortezomib patients. These findings suggest a potential role for MRP1 and MDR1 SNPs in modulating the long-term outcome of relapsed and/or refractory myeloma patients treated with PLD + bortezomib. Moreover, they support prospective studies to determine if such data could be used to tailor therapy to the genetic makeup of individual patients

Characterization of HCV Interactions with Toll-Like Receptors and RIG-I in Liver Cells

The aim of this study was to examine the mechanisms of IFN induction and viral escape. In order to accomplish the goal we compared our new hepatoma cell line LH86, which has intact TLR3 and RIG-I expression and responds to HCV by inducing IFN, with Huh7.5 cells which lack those features.The initial interaction of LH86 cells, Huh7.5 cells or their transfected counter parts (LH86 siRIG-I, siTLR3 or siTLR7 and Huh7.5 RIG-I, TLR3 or TLR7) after infection with HCV (strain JFH-1) was studied by measuring the expression levels of IFNβ, TRAIL, DR4, DR5 and their correlation to viral replication.HCV replicating RNA induces IFN in LH86 cells. The IFN induction system is functional in LH86, and the expression of the RIG-I and TLR3 in LH86 is comparable to the primary hepatocytes. Both proteins appear to play important roles in suppression of viral replication. We found that innate immunity against HCV is associated with the induction of apoptosis by RIG-I through the TRAIL pathway and the establishment of an antiviral state by TLR3. HCV envelope proteins interfere with the expression of TLR3 and RIG-I.These findings correlate with the lower expression level of PRRs in HCV chronic patients and highlight the importance of the PRRs in the initial interaction of the virus and its host cells. This work represents a novel mechanism of viral pathogenesis for HCV and demonstrates the role of PRRs in viral infection