Palo Alto, CA, United States

Innovation Center Denmark
Palo Alto, CA, United States

Innovation Center Denmark facilitates the entry of technology based Danish companies into Silicon Valley, connects research, capital and companies and innovates business models and market strategies. Innovation Center Denmark is a joint effort between The Danish Ministry of Foreign Affairs and The Ministry of Science, Technology and Innovation; a new type of commercial mission located in technological hot spots around the world. Wikipedia.

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Vadodaria K.C.,University of Zürich | Vadodaria K.C.,ETH Zurich | Brakebusch C.,Innovation Center Denmark | Suter U.,ETH Zurich | And 2 more authors.
Journal of Neuroscience | Year: 2013

The molecular mechanisms underlying the generation, maturation, and integration of new granule cells generated throughout life in the mammalian hippocampus remain poorly understood. Small Rho GTPases, such as Cdc42 and Rac1, have been implicated previously in neural stem/progenitor cell (NSPC) proliferation and neuronal maturation during embryonic development. Here we used conditional genetic deletion and virus-based loss-of-function approaches to identify temporally distinct functions for Cdc42 and Rac1 in adult hippocampal neurogenesis. We found that Cdc42 is involved in mouse NSPC proliferation, initial dendritic development, and dendritic spine maturation. In contrast, Rac1 is dispensable for early steps of neuronal development but is important for late steps of dendritic growth and spine maturation. These results establish cell-autonomous and stage-specific functions for the small Rho GTPases Cdc42 and Rac1 in the course of adult hippocampal neurogenesis. © 2013 the authors.

Grandvuinet A.S.,Copenhagen University | Vestergaard H.T.,Danish Medicines Agency | Rapin N.,Innovation Center Denmark | Steffansen B.,Copenhagen University
Journal of Pharmacy and Pharmacology | Year: 2012

Objectives This review provides an overview of intestinal human transporters for organic anions and stresses the need for standardization of the various in-vitro methods presently employed in drug-drug interaction (DDI) investigations. Key findings Current knowledge on the intestinal expression of the apical sodium-dependent bile acid transporter (ASBT), the breast cancer resistance protein (BCRP), the monocarboxylate transporters (MCT) 1, MCT3-5, the multidrug resistance associated proteins (MRP) 1-6, the organic anion transporting polypetides (OATP) 2B1, 1A2, 3A1 and 4A1, and the organic solute transporter α/β (OSTα/β) has been covered along with an overview of their substrates and inhibitors. Furthermore, the many challenges in predicting clinically relevant DDIs from in-vitro studies have been discussed with focus on intestinal transporters and the various methods for deducting in-vitro parameters for transporters (Km/Ki/IC50, efflux ratio). The applicability of using a cut-off value (estimated based on the intestinal drug concentration divided by the Ki or IC50) has also been considered. Summary A re-evaluation of the current approaches for the prediction of DDIs is necessary when considering the involvement of other transporters than P-glycoprotein. Moreover, the interplay between various processes that a drug is subject to in-vivo such as translocation by several transporters and dissolution should be considered. © 2012 Royal Pharmaceutical Society.

Riis A.,University of Aalborg | Riis A.,Research Unit for General Practice | Rathleff M.S.,University of Aalborg | Rathleff M.S.,Innovation Center Denmark | And 2 more authors.
Bone and Joint Journal | Year: 2014

The optimal timing of total knee replacement (TKR) in patients with osteoarthritis, in relation to the severity of disease, remains controversial. This prospective study was performed to investigate the effect of the severity of osteoarthritis and other commonly available pre-and post-operative clinical parameters on the clinical outcome in a consecutive series of cemented TKRs. A total of 176 patients who underwent unilateral TKR were included in the study. Their mean age was 68 years (39 to 91), 63 (36%) were male and 131 knees (74%) were classified as grade 4 on the Kellgren-Lawrence osteoarthritis scale. A total of 154 patients (87.5%) returned for clinical review 12 months post-operatively, at which time the outcome was assessed using the Knee Society score. A low radiological severity of osteoarthritis was not associated with pain 12 months postoperatively. However, it was significantly associated with an inferior level of function (p = 0.007), implying the need for increased focus on all possible reasons for pain in the knee and the forms of conservative treatment which are available for patients with lower radiological severity of osteoarthritis. © 2014 The British Editorial Society of Bone &Joint Surgery.

Ehimen E.A.,University of Aalborg | Holm-Nielsen J.-B.,University of Aalborg | Poulsen M.,Innovation Center Denmark | Boelsmand J.E.,Innovation Center Denmark
Renewable Energy | Year: 2013

The anaerobic digestion of outdoor cultivated Rhizoclonium biomass was investigated in this study. The influence of applying mechanical and biological pre-treatment methods prior to the biomass digestion on the overall methane yields was examined. The results show that the application of a combined biomass blending (<0.1 mm length) and an enzymatic pre-treatment improved the methane yields by >20% compared to use of a mechanical size reduction method alone. The methane yields from Rhizoclonium biomass were however observed to be considerably lower than those of other algae species from the literature. © 2012 Elsevier Ltd.

Spangenberg J.H.,Sustainable Europe Research Institute SERI Germany E.V. | Fuad-Luke A.,Innovation Center Denmark | Blincoe K.,Innovation Center Denmark
Journal of Cleaner Production | Year: 2010

Nowadays design is faced with the challenge to contribute to the transition towards a sustainable society. Design for Sustainability (DfS) is the response to this challenge. It includes but goes beyond what Design for the Environment or ecodesign provides, by integrating social, economic, environmental and institutional aspects and by offering opportunities to get involved, express one's own identity beyond consuming standardised mass products. DEEDS, a Leonardo research project, had the mission to embed sustainability in design and design in sustainability. For this behalf, the project partners approached the issue from the angles of design, sustainability science and sustainable consumption analysis, developing tools and rules (the SCALES principles) to support DfS and to incorporate it into design education and practice. The paper describes the framework conditions as explored by sustainable consumption research, the obstacles identified by DEEDS and gives hints how to overcome them based in the lessons learnt in the course of the project. © 2010 Elsevier B.V. All rights reserved.

Nagamori I.,University of California at Irvine | Adam Cruickshank V.,Innovation Center Denmark | Sassone-Corsi P.,University of California at Irvine
Journal of Cell Science | Year: 2011

SummaryDuring mammalian spermatogenesis, the mouse VASA homolog (MVH; also known as DDX4), a germ-cell-specific DEAD-box type RNA-binding protein, localizes in a germline-specific RNA granule termed the chromatoid body (CB). Genetic analyses have revealed that MVH is essential for progression through spermatogenesis, although the molecular mechanisms of its function remain elusive. We found that the acetyltransferase Hat1, and its cofactor, p46, are specifically colocalized with MVH in the CB and acetylate MVH at Lys405, leading to inactivation of its RNA-binding activity. Notably, the acetylation is developmentally regulated, paralleling the temporally regulated colocalization of Hat1 and p46 in the CB. We have identified 858 mRNAs as MVH targets, a large proportion of which correspond to previously known translationally arrested genes. Importantly, eIF4B mRNA, a target of MVH, is selectively released from the MVH-ribonucleoprotein (RNP) complex when MVH is acetylated, paralleling an increase in eIF4B protein. These findings reveal a previously unknown signaling pathway that links acetylation to RNA processing in the control of spermatogenesis. © 2011. Published by The Company of Biologists Ltd.

Lohse B.,Copenhagen University | Nielsen A.L.,Novo Nordisk AS | Kristensen J.B.L.,Copenhagen University | Helgstrand C.,Copenhagen University | And 5 more authors.
Angewandte Chemie - International Edition | Year: 2011

How low can you go? The natural substrate for the epigenetic regulators PHF8, JmjD2A, and JmjD2C (lysine demethylases), a peptide consisting of 39 amino acid residues, can be truncated to 14, 8, and 4 amino acids, respectively, while maintaining catalytic activity (see picture). Inhibitors were prepared by attaching small molecules to the truncated substrates. Selective inhibition of JmjD2C over JmjD2A and PHF8 was possible. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thomsen F.B.,Copenhagen University | Christensen I.J.,Innovation Center Denmark | Brasso K.,Copenhagen University | Roder M.A.,Copenhagen University | Iversen P.,Copenhagen University
BJU International | Year: 2014

Objectives: • To elucidate the role of prostate-specific antigen (PSA) doubling time (PSAdt) as a progression criterion in patients with low-risk prostate cancer managed by active surveillance (AS). • To assess the correlation between PSAdt during AS and final histopathology after radical prostatectomy (RP) in patients meeting predefined progression criteria. Patients and Methods: • A total of 258 consecutive patients on an AS programme were included in the study. • The PSAdt was calculated in patients with two or more PSA values, and 95% confidence intervals (CIs) were calculated in patients with four or more PSA values. • Progression risk groups were defined as follows: high-risk: PSAdt <3 years, rebiopsy Gleason score (GS) ≥4 + 3, more than three positive biopsy cores, and/or bilateral tumour or cT ≥2c disease; intermediate-risk: PSAdt 3-5 years, GS = 3 + 4 or cT2b disease; and low-risk: PSAdt >5 years, without histopathological or clinical progression. • Definitive treatment was recommended for patients in the high-risk group and treatment options were discussed with those in the intermediate-risk group. Results: • A total of 2291 PSA values obtained during AS were available, of which 2071 were considered valid in the 258 patients. • PSAdt values with 95% CIs were calculated in 221 patients based on a median of 8 PSA values. • The 95% CIs for PSAdt overlapped considerably and in up to 91% of the patients, the 95% CIs overlapped among the risk group definitions. • A total of 26% (68/258 patients) underwent RP after meeting the progression criteria. • There was no association between preoperative PSAdt and final histopathology (P = 0.87). Conclusion: • The uncertainty of calculated PSAdt during AS leads to a significant risk of patients being misclassified in terms of risk of progression, which limits the use of PSAdt in the management of patients on AS. © 2013 The Authors.

Nasr I.,University of Iowa | Attaluri A.,University of Iowa | Hashmi S.,University of Iowa | Gregersen H.,Innovation Center Denmark | Rao S.S.C.,University of Iowa
Neurogastroenterology and Motility | Year: 2010

Background There is limited and conflicting data regarding the role of esophageal hypersensitivity in the pathogenesis of functional chest pain (FCP). We examined esophageal sensori-motor properties, mechanics, and symptoms in subjects with FCP. Methods Esophageal balloon distension test was performed using impedance planimetry in 189 (m/f = 57/132) consecutive subjects with non-cardiac, non-reflux chest pain, and 36 (m/f = 16/20) healthy controls. The biomechanical and sensory properties of subjects with and without esophageal hypersensitivity were compared with controls. The frequency, intensity, and duration of chest pain were assessed. Key Results One hundred and forty-three (75%) subjects had esophageal hypersensitivity and 46 (25%) had normal sensitivity. Typical chest pain was reproduced in 105/143 (74%) subjects. Subjects with hypersensitivity demonstrated larger cross-sectional area (P < 0.001), decreased esophageal wall strain (P < 0.001) and distensibility (P < 0.001), and lower thresholds for perception (P < 0.01), discomfort (P < 0.01), and pain (P < 0.01) compared to those without hypersensitivity or healthy controls. Chest pain scores (mean ± SD) for frequency, intensity and duration were 2.5 ± 0.3, 2.2 ± 0.2, and 2.2 ± 0.2, respectively, and were similar between the two patient groups. Conclusions & Inferences Seventy-five per cent of subjects with FCP demonstrate esophageal hypersensitivity. Visceral hyperalgesia and sensori-motor dysfunction of the esophagus play a key role in the pathogenesis of chest pain. © 2010 Blackwell Publishing Ltd.

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