47 results on '"Nielsen, Christian"'
Search Results
2. Role of oxygen within end group substituents on film morphology and charge carrier transport in thiophene/phenylene small-molecule semiconductors
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Waliszewski, Witold, Parr, Zachary S., Michalska, Agnieszka, Halaksa, Roman, Zajaczkowska, Hanna, Sleczkowski, Piotr, Neophytou, Marios, Luszczynska, Beata, Blom, Paul W.M., Nielsen, Christian B., Marszalek, Tomasz, and Pisula, Wojciech
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- 2022
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3. Quantification of the pro-form of human complement component factor D (adipsin)
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Henriksen, Maiken Lumby, Nielsen, Christian, Pedersen, Dennis, Andersen, Gregers Rom, Thiel, Steffen, Palarasah, Yaseelan, and Hansen, Soren Werner Karlskov
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- 2022
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4. Persistently reduced humoral and sustained cellular immune response from first to third SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients
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Bajwa, Hamza Mahmood, Novak, Frederik, Nilsson, Anna Christine, Nielsen, Christian, Holm, Dorte K., Østergaard, Kamilla, Witt, Agnes Hauschultz, Byg, Keld-Erik, Johansen, Isik S., Mittl, Kristen, Rowles, William, Zamvil, Scott S., Bove, Riley, Sabatino, Joseph J., and Sejbaek, Tobias
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- 2022
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5. Product Design for Matrix-Structured Manufacturing Systems
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Nielsen, Christian P. and Yu, Fei
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- 2022
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6. Humoral immune response following SARS-CoV-2 mRNA vaccination concomitant to anti-CD20 therapy in multiple sclerosis
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Novak, Frederik, Nilsson, Anna Christine, Nielsen, Christian, Holm, Dorte K., Østergaard, Kamilla, Bystrup, Anna, Byg, Keld-Erik, Johansen, Isik S., Mittl, Kristen, Rowles, William, Mcpolin, Kira, Spencer, Collin, Sagan, Sharon, Gerungan, Chloe, Wilson, Michael R., Zamvil, Scott S., Bove, Riley, Sabatino, Joseph J., and Sejbaek, Tobias
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- 2021
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7. Bystander interventions and survival following out-of-hospital cardiac arrest at Copenhagen International Airport
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Gantzel Nielsen, Christian, Andelius, Linn Charlotte, Hansen, Carolina Malta, Blomberg, Stig Nikolaj Fasmer, Christensen, Helle Collatz, Kjølbye, Julie Samsøe, Tofte Gregers, Mads Christian, Ringgren, Kristian Bundgaard, and Folke, Fredrik
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- 2021
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8. A data-driven approach for Decision-Making support of factory simulation solutions
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Yu, Fei and Nielsen, Christian P.
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- 2020
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9. Digital Twins and Blockchain – Proof of Concept
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Nielsen, Christian Petersson, da Silva, Elias Ribeiro, and Yu, Fei
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- 2020
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10. Operating Digital Manufacturing in Industry 4.0: the role of advanced manufacturing technologies
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da Silva, Elias Ribeiro, Shinohara, Ana Carolina, Nielsen, Christian Petersson, de Lima, Edson Pinheiro, and Angelis, Jannis
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- 2020
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11. Low-Cost 3D Scanning in a Smart Learning Factory
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Nielsen, Christian P., Malik, Ali A., Hansen, David G., and Bilberg, Arne
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- 2019
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12. Secondary kinetic deuterium isotope effects. The CC cleavage of labeled tetramethylethylenediamine radical cations—Who gets to keep the electron?
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Nielsen, Christian Bech and Hammerum, Steen
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- 2017
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13. Bis-lactam-based donor polymers for organic solar cells: Evolution by design
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Rumer, Joseph W., Schroeder, Bob C., Nielsen, Christian B., Ashraf, Raja S., Beatrup, Daniel, Bronstein, Hugo, Cryer, Samuel J., Donaghey, Jenny E., Holliday, Sarah, Hurhangee, Michael, James, David I., Lim, Stefanie, Meager, Iain, Zhang, Weimin, and McCulloch, Iain
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- 2014
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14. A specific assay for quantification of human C4c by use of an anti-C4c monoclonal antibody
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Pilely, Katrine, Skjoedt, Mikkel-Ole, Nielsen, Christian, Andersen, Thomas Emil, Louise Aabom, Anne, Vitved, Lars, Koch, Claus, Skjødt, Karsten, and Palarasah, Yaseelan
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- 2014
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15. P2X7 receptor-deficient mice are susceptible to bone cancer pain
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Hansen, Rikke Rie, Nielsen, Christian K., Nasser, Arafat, Thomsen, Stine I.M., Eghorn, Laura F., Pham, Yen, Schulenburg, Cecilia, Syberg, Susanne, Ding, Ming, Stojilkovic, Stanko S., Jorgensen, Niklas R., and Heegaard, Anne-Marie
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- 2011
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16. Influence of side chain symmetry on the performance of poly(2,5-dialkoxy- p-phenylenevinylene): fullerene blend solar cells
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Tuladhar, Sachetan M., Sims, Marc, Choulis, Stelios A., Nielsen, Christian B., George, Wayne. N., Steinke, Joachim H.G., Bradley, Donal D.C., and Nelson, Jenny
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- 2009
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17. Gauge-origin independent magnetizabilities from hybrid quantum mechanics/molecular mechanics models: Theory and applications to liquid water
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Aidas, Kestutis, Kongsted, Jacob, Nielsen, Christian B., Mikkelsen, Kurt V., Christiansen, Ove, and Ruud, Kenneth
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- 2007
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18. 17-β Estradiol and 4-nonylphenol delay smolt development and downstream migration in Atlantic salmon, Salmo salar
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Madsen, Steffen S, Skovbølling, Søren, Nielsen, Christian, and Korsgaard, Bodil
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- 2004
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19. Versatile and recyclable double-network PVA/cellulose hydrogels for strain sensors and triboelectric nanogenerators under harsh conditions.
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Wang, Yaquan, Zhang, Yuan, Ren, Peng, Yu, Simiao, Cui, Peng, Nielsen, Christian B., Abrahams, Isaac, Briscoe, Joe, and Lu, Yao
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Versatile and recyclable conductive hydrogels with long-term environmental adaptability and mechanical stability have attracted tremendous attention in wearable smart electronics. Here, double-network (DN) polyvinyl alcohol (PVA)/cellulose hydrogels were constructed after introducing a conductive rigid cellulose/Zn
2+ /Ca2+ network into a soft PVA/borax network. The resultant hydrogels possessed good mechanical and self-adhesive properties, along with transparency, recyclability, and remarkable resistance to freezing. They showed 30-day non-drying properties due to the presence of hygroscopic salts through a dynamic moisture adsorption and desorption process. Dehydrated hydrogels can return to their original states via self-regeneration under high relative humidity. Hydrogel-based strain sensors retained good sensitivity and a wide sensing range during the wide working temperature ranging from −40 °C to 50 °C and after recycling. Additionally, conductive hydrogels were integrated into triboelectric nanogenerators (TENGs) functioning as energy harvesters for powering electronics. TENGs retained stable electrical outputs even under harsh conditions and after recycling. Hydrogels were also assembled into flexible self-powered biomechanical sensors and tactile sensors. Thermally reversible interactions in composite hydrogels enabled their good recyclability, thereby reducing economic costs and environmental impacts caused by e-wastes. This work demonstrates the great potential of versatile and recyclable hydrogels with good environmental and mechanical stability in wearable smart electronics under harsh conditions. [Display omitted] • The double-network hydrogels consist of rigid cellulose and soft PVA networks. • The double-network hydrogels are versatile, environmentally stable and recyclable. • The demonstration of sensors in information transmission and human motion detection. • The demonstration of TENGs in sustainable power supply and self-powered sensors. • The demonstration of strain sensors and TENGs under harsh conditions [ABSTRACT FROM AUTHOR]- Published
- 2024
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20. Introduction of a New Treatment Algorithm Reduces the Number of Periprosthetic Femoral Fractures After Primary Total Hip Arthroplasty in Elderly Females.
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Omari, Adam, Nielsen, Christian S., Husted, Henrik, Otte, Kristian S., Troelsen, Anders, and Gromov, Kirill
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Background: Increasing global usage of cementless prostheses in total hip arthroplasty (THA) presents a challenge, especially for elderly patients. To reduce the risk of early periprosthetic femoral fractures (PFFs), a new treatment algorithm for females older than 60 years undergoing primary THA was introduced. The aim of this study was to determine the impact of the new treatment algorithm on the early risk of perioperative and postoperative PFFs and guideline compliance.Methods: A total of 2405 consecutive THAs that underwent primary unilateral THA at our institution were retrospectively identified in the period January 1, 2013-December 31, 2018. A new treatment algorithm was introduced on April 1, 2017 with female patients aged older than 60 years intended to receive cemented femoral components. Before this, all patients were scheduled to receive cementless femoral components. Demographic data, number of perioperative and postoperative PFFs, and surgical compliance were recorded, analyzed, and intergroup differences compared.Results: The utilization of cemented components in female patients older than 60 years increased from 12.3% (n = 102) to 82.5% (n = 264). In females older than 60 years, a significant reduction in the risk in early postoperative and intraoperative PFF after introduction of the new treatment algorithm was seen (4.57% vs 1.25%; P = .007 and 2.29% vs 0.31%; P = .02, respectively). Overall risk for postoperative and intraoperative fractures combined was also reduced in the entire cohort (4.1% vs 2.0%; P = .01).Conclusion: Use of cemented fixation of the femoral component in female patients older than 60 years significantly reduces the number of PFFs. Our findings support use of cemented femoral fixation in elderly female patients. [ABSTRACT FROM AUTHOR]- Published
- 2020
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21. Harnessing AI to unmask Copenhagen's invisible air pollutants: A study on three ultrafine particle metrics.
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Amini, Heresh, Bergmann, Marie L., Taghavi Shahri, Seyed Mahmood, Tayebi, Shali, Cole-Hunter, Thomas, Kerckhoffs, Jules, Khan, Jibran, Meliefste, Kees, Lim, Youn-Hee, Mortensen, Laust H., Hertel, Ole, Reeh, Rasmus, Gaarde Nielsen, Christian, Loft, Steffen, Vermeulen, Roel, Andersen, Zorana J., and Schwartz, Joel
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MACHINE learning ,AIR pollutants ,REGRESSION trees ,STANDARD deviations ,INDEPENDENT variables ,CITIES & towns - Abstract
Ultrafine particles (UFPs) are airborne particles with a diameter of less than 100 nm. They are emitted from various sources, such as traffic, combustion, and industrial processes, and can have adverse effects on human health. Long-term mean ambient average particle size (APS) in the UFP range varies over space within cities, with locations near UFP sources having typically smaller APS. Spatial models for lung deposited surface area (LDSA) within urban areas are limited and currently there is no model for APS in any European city. We collected particle number concentration (PNC), LDSA, and APS data over one-year monitoring campaign from May 2021 to May 2022 across 27 locations and estimated annual mean in Copenhagen, Denmark, and obtained additionally annual mean PNC data from 6 state-owned continuous monitors. We developed 94 predictor variables, and machine learning models (random forest and bagged tree) were developed for PNC, LDSA, and APS. The annual mean PNC, LDSA, and APS were, respectively, 5523 pt/cm
3 , 12.0 μm2 /cm3 , and 46.1 nm. The final R2 values by random forest (RF) model were 0.93 for PNC, 0.88 for LDSA, and 0.85 for APS. The 10-fold, repeated 10-times cross-validation R2 values were 0.65, 0.67, and 0.60 for PNC, LDSA, and APS, respectively. The root mean square error for final RF models were 296 pt/cm3 , 0.48 μm2 /cm3 , and 1.60 nm for PNC, LDSA, and APS, respectively. Traffic-related variables, such as length of major roads within buffers 100–150 m and distance to streets with various speed limits were amongst the highly-ranked predictors for our models. Overall, our ML models achieved high R2 values and low errors, providing insights into UFP exposure in a European city where average PNC is quite low. These hyperlocal predictions can be used to study health effects of UFPs in the Danish Capital. [Display omitted] • Developed first machine-learning models for three UFP metrics in Copenhagen, Denmark. • Annual mean PNC, LDSA, and average particle size (APS) were 5523 pt/cm3 , 12.0 μm2 /cm3 , and 46.1 nm. • The cross-validated R2 values were 0.65, 0.67, and 0.60 for PNC, LDSA, and APS. • Novel insights into the spatial variation of UFP exposure metrics in a European city. • Providing the opportunity to study PNC/LDSA health effects and effect modification by APS. [ABSTRACT FROM AUTHOR]- Published
- 2024
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22. 149. Is serum 25-hydroxyvitamin D associated to blood pressure in pregnancy and preeclampsia development?
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Andersen, Louise Bjørkholt, Birukov, Anna, Jørgensen, Jan Stener, Sørensen, Grith Lykke, Nielsen, Christian, Barington, Torben, Dechend, Ralf, and Christesen, Henrik Thybo
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- 2018
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23. Medial Overhang of the Tibial Component Is Associated With Higher Risk of Inferior Knee Injury and Osteoarthritis Outcome Score Pain After Knee Replacement.
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Nielsen, Christian S., Nebergall, Audrey, Huddleston, James, Kallemose, Thomas, Malchau, Henrik, and Troelsen, Anders
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Background: The aim of this prospective multicenter study is to investigate the association among (1) tibial site-specific overhang of medial, anterior, and lateral overhang in relation to Knee Injury and Osteoarthritis Outcome Score pain 1 year after surgery (1 Y KOOS pain) and (2) the malalignment of TKA components including overall malalignment in relation to 1 Y KOOS pain.Methods: From 10 centers, across 4 continents, 323 patients were enrolled from October 2011 to February 2014. Radiographs were analyzed for tibial overhang on medial, anterior, and lateral site and for overall, tibial, femur, and combined malalignment. A 1 Y KOOS pain score <70 represented an unsatisfactory pain level.Results: A significant association was observed between medial overhang and 1 Y KOOS pain with a cut-off of <70 (P = .04), with an odds ratio of 0.46. No significant associations were observed among the independent variables of lateral and anterior overhang or for overall, tibial, femoral, and combined component malalignment, and the dependent variable of 1 Y KOOS pain <70.Conclusion: This prospective multicenter study showed a significant association between medial overhang of the tibial component and a 1 Y KOOS pain <70. The related odds ratio was 0.46, which demonstrates that medial overhang may lead to a 54% reduced chance for entering an acceptable pain category 1 year after surgery when receiving a TKA. [ABSTRACT FROM AUTHOR]- Published
- 2018
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24. Low Risk of Thromboembolic Events After Routine Administration of Tranexamic Acid in Hip and Knee Arthroplasty.
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Madsen, Rune V., Nielsen, Christian S., Kallemose, Thomas, Husted, Henrik, and Troelsen, Anders
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Background: The blood-conserving effect of intravenous (IV) tranexamic acid (TXA) is well-documented for total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, the risk of thromboembolic (TE) events after routine use of TXA is unclear and the safety profile is debated. This retrospective study investigates patient characteristics, occurrences, and predictors of TE events after routine administration of IV TXA in THA and TKA.Methods: Three thousand one hundred fifty-nine THA or TKA procedures performed from 2007-2013 at our institution were included. IV TXA, 1 g, was administered preoperatively if not contraindicated. Relevant patient characteristics and comorbidity information were extracted locally from the database. Data on TE events occurring within 90 days postoperatively came from The Danish National Patient Registry. Patient characteristics, comorbidities, and TE events were compared between TXA groups. A logistic regression model was used to evaluate predictors of TE events.Results: Of 3159 procedures, 2766 (87.6%) received TXA (TXA+ group) preoperatively, whereas 393 (12.4%) did not (TXA- group). Mean age, distributions of gender, American Society of Anesthesiologists score, anesthesia method, duration of surgery, diagnosis, and survival status were all statistically significant different (P values <.05) between TXA groups. The studied comorbidities were all significantly different (TXA+ vs TXA- group; P values ≤.002). We found 31 (1.0%) TE events out of 3159 procedures, with no significant group difference in TE events (TXA+: 27 out of 2766 = 1.0%, TXA-: 4 out of 393 = 1.0%, P value = .55 for any event). For the TXA+ group, 0.5% suffered from deep venous thrombosis, 0.3% from acute myocardial infarction, and 0.2% from a pulmonary embolism. In the TXA+ group, higher age (odds ratio [OR] = 1.06, 95% confidence interval = 1.02-1.11, P = .005) and present cardiovascular disease (OR = 4.78, 95% confidence interval = 1.72-13.28, P = .003) were associated with an increased risk of TE events.Conclusion: The findings suggest that routine use of IV TXA for TKA and THA as safe with low occurrence of TE events, although a large prospective trial should confirm this. [ABSTRACT FROM AUTHOR]- Published
- 2017
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25. No Effect of a Bipolar Sealer on Total Blood Loss or Blood Transfusion in Nonseptic Revision Knee Arthroplasty-A Prospective Study With Matched Retrospective Controls.
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Nielsen, Christian Skovgaard, Gromov, Kirill, Jans, Øivind, Troelsen, Anders, and Husted, Henrik
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Background: Postoperative anemia is frequent after revision of total knee arthroplasty (TKA) with reported transfusion rates up to 83%. Despite increased efforts of reducing blood loss and enhancing fast recovery within the fast-track setup, a considerable transfusion rate is still evident. The aim of this study was therefore to evaluate the effect of a bipolar sealer on blood loss and transfusion in revision TKA.Methods: In this single-center prospective cohort study with retrospective controls, 51 patients were enrolled in a fast-track setup for revision TKA without the use of a tourniquet. Twenty-five prospectively enrolled patients received treatment with both a bipolar sealer and electrocautery, whereas 26 patients had received treatment with a conventional electrocautery only in the retrospective group.Results: No significant differences were found neither for calculated blood loss, with 1397 (standard deviation, ± 452) mL in the bipolar sealer group vs 1452 (SD, ± 530) mL in the control group (P = .66), nor for blood transfusion rates of 53% and 46% (P = .89), respectively. Four controls were readmitted within 90 days follow-up.Conclusion: The use of a bipolar sealer in a TKA revision setting without the use of a tourniquet did not reduce blood loss or blood transfusion rates. [ABSTRACT FROM AUTHOR]- Published
- 2017
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26. Obese Patients Achieve Good Improvements in Patient-Reported Outcome Measures After Medial Unicompartmental Knee Arthroplasty Despite a Lower Preoperative Score.
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Bagge, Anders, Jensen, Christian B., Mikkelsen, Mette, Gromov, Kirill, Nielsen, Christian S., and Troelsen, Anders
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In this study, we examined the association between obesity and patient-reported outcome measures after medial unicompartmental knee arthroplasty (MUKA), assessed through score changes, Patient Acceptable Symptom State (PASS), and minimal important change (MIC). Second, the association between obesity and early readmissions was examined. A total of 450 MUKAs (mean body mass index [BMI] 30.3, range, 19.6-53.1), performed from February 2016 to December 2020, were grouped using BMI: <30, 30-34.9, and >34.9. Oxford Knee Score (OKS), Forgotten Joint Score (FJS), and Activity and Participation Questionnaire (APQ) were assessed preoperatively and at 3, 12, and 24 months, postoperatively. The 12-month PASS and MIC were also assessed, defining PASS as OKS = 30, MIC-OKS as change in OKS = 8, and MIC-FJS as change in FJS = 14. No significant differences in OKS change were found between BMI groups. After 12 months, patients who had a BMI of 30-34.9 had lower change in FJS (estimate −8.1, 95% CI −14.9 to −1.4) and were less likely to reach PASS (odds ratio 0.4, 95% CI 0.2-0.7) as well as MIC-FJS (odds ratio 0.5, 95% CI 0.2-0.9). Both obese groups had lower change in APQ after 12 months. Differences in 90-day readmission rates were nonsignificant between groups. Our findings of no differences in OKS improvement between BMI groups and achieving MIC for BMI > 34.9 suggest good improvements in obese patients despite lower preoperative scores, supporting contemporary indications for MUKA. Lower APQ development and achievement of 12-month PASS may be used when addressing expectations of recovery. [ABSTRACT FROM AUTHOR]
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- 2023
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27. The origins and processing of ultra fine anaphase DNA bridges.
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Liu, Ying, Nielsen, Christian F, Yao, Qi, and Hickson, Ian D
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ANAPHASE , *DNA structure , *MITOSIS , *IMMUNOFLUORESCENCE , *STAINS & staining (Microscopy) , *CELL physiology - Abstract
Ultra-fine DNA bridges (UFBs) are a recently identified class of mitotic DNA structures that cannot be visualized using conventional DNA staining methods (e.g. using DAPI). Their existence can currently only be revealed by immuno-fluorescent staining for proteins that bind to them, including PICH and BLM. UFBs become visible in the anaphase of mitosis, and can persist into telophase in rare cases. There are at least three different types of UFBs that can be distinguished according to the chromosomal loci from which they originate. However, it remains largely unknown how these UFBs are generated or resolved in the cell. In this article, we will review our current understanding of different types of UFBs and the potential functional role of the proteins that have been shown to be associated with them. [ABSTRACT FROM AUTHOR]
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- 2014
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28. ADAM12-mediated focal adhesion formation is differently regulated by β1 and β3 integrins
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Thodeti, Charles Kumar, Fröhlich, Camilla, Nielsen, Christian Kamp, Takada, Yoshikazu, Fässler, Reinhard, Albrechtsen, Reidar, and Wewer, Ulla M.
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- 2005
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29. Crack healing in cross-ply composites observed by dynamic mechanical analysis.
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Nielsen, Christian and Nemat-Nasser, Sia
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FRACTURE mechanics , *COMPOSITE materials , *CARBON fibers , *FRACTURE toughness , *RESIDUAL stresses - Abstract
Cross-ply composites with healable polymer matrices are characterized using dynamic mechanical analysis (DMA). The [90,0] s samples are prepared by embedding layers of unidirectional glass or carbon fibers in 2MEP4FS, a polymer with thermally reversible covalent cross-links, which has been shown to be capable of healing internal cracks and fully recovering fracture toughness when the crack surfaces are kept in contact. After fabrication, cracks in the composites' transverse plies are observed due to residual thermal stresses introduced during processing. Single cantilever bending DMA measurements show the samples exhibit periods of increasing storage moduli with increasing temperature. These results are accurately modeled as a one-dimensional composite, which captures the underlying physics of the phenomenon. The effect of cracks on the stiffness is accounted for by a shear-lag model. The predicted crack density of the glass fiber composite is shown to fall within a range observed from microscopy images. Crack healing occurs as a function of temperature, with chemistry and mechanics-based rationales given for the onset and conclusion of healing. The model captures the essential physics of the phenomenon and yields results in accord with experimental observations. [ABSTRACT FROM AUTHOR]
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- 2015
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30. Thermally reversible cross-links in a healable polymer: Estimating the quantity, rate of formation, and effect on viscosity.
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Nielsen, Christian, Weizman, Haim, and Nemat-Nasser, Sia
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CROSSLINKED polymers , *VISCOSITY , *DIELS-Alder reaction , *THERMAL analysis , *RING formation (Chemistry) , *PREPOLYMERS , *GLASS transition temperature - Abstract
Abstract: The conversion behavior of 2MEP4FS, a polymer with thermally reversible Diels–Alder cross-links, is modeled. A processing method is developed to create small, homogeneous prepolymer samples. The glass transition temperature of the prepolymer is estimated using temperature modulated differential scanning calorimetry and equated with the conversion of the polymer. Comparing the measured energy with the literature and computational estimates, the fully cured polymer appears to have a large portion of its moieties unreacted. An autocatalytic model is considered to approximate the reaction rate of 2MEP4FS as a function of conversion and temperature. Outside of the fitted temperature range, the model underpredicts the reaction rates at room temperature and 100 °C. Manual mixing of the monomers is determined to be inadequate to obtain a maximum level of cross-linking. Viscosity measurements made at room temperature and elevated temperatures are correlated with the conversion of the prepolymer. [Copyright &y& Elsevier]
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- 2014
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31. Recent advances in transistor performance of polythiophenes.
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Nielsen, Christian B. and McCulloch, Iain
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TRANSISTORS , *PERFORMANCE evaluation , *ELECTRIC properties of polythiophenes , *CONDUCTING polymers , *POLYMERIZATION , *FIELD-effect transistors , *ELECTROCHROMIC devices - Abstract
Abstract: Polythiophenes have long played a major role in the field of conducting polymers due to their relative ease of synthesis, good thermal and oxidative stability, high charge carrier mobility and ease of processing and they have found widespread use in electronic applications such as field-effect transistors (FETs), organic photovoltaics (OPVs), light-emitting diodes (LEDs) and electrochromic displays (ECDs). In this review, we summarize the most important synthetic approaches to thiophene-, thienothiophene- and other fused thiophene-based polymers, highlight a number of significant findings relating to their properties with an emphasis on device performance in organic field-effect transistors and reflect on existing challenges and future opportunities in the field. [Copyright &y& Elsevier]
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- 2013
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32. CD4+ CD31+ recent thymic emigrants in CHD7 haploinsufficiency (CHARGE syndrome): A case.
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Assing, Kristian, Nielsen, Christian, Kirchhoff, Maria, Madsen, Hans O., Ryder, Lars P., and Fisker, Niels
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CD4 antigen , *CD31 antigen , *CHARGE syndrome , *LYMPHOCYTE count , *INFANT death , *DNA helicases , *HEALTH outcome assessment , *AUTOIMMUNE diseases , *T cell receptors - Abstract
Abstract: Lymphocyte counts <2000cells/μL are associated with early death in infants with CHARGE (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) syndrome and CHD7 haploinsufficiency. Absence of recent thymic emigrants is also accompanied by an Omenn-like syndrome and infant death in CHD7 haploinsufficiency. Studies positively identifying recent thymic emigrants, in relation to CHD7 haploinsufficiency, are non-existent. Thirty two months of flow-cytometric work-up of an athymic (evaluated by four chest X-rays) infant, with a novel CHD7 deletion, demonstrated sparse (<50cells/mm3) but continuous egress of recent thymic emigrants (CD3+ CD4+ CD45RA+ CD45RO− CD31+) and homeostatic lymphocyte expansion. Infectious or autoimmune episodes (e.g., Omenn-like syndrome) were not detected (despite lymphocyte counts <2000cells/μL) and excellent vaccination (tetanus, Haemophilus influenzae type B and pneumococcal conjugate vaccines) and proliferation (anti-CD3 and anti-CD28 stimulated) responses were recorded. Her CD4+ T cells displayed Gaussian distributed TCR (CDR3) spectratypes (22 functional Vβ families). Her CD4+ T cell profile was also characterized by a slightly increased proportion CD4+ CD25+ FoxP3+ T cells. Since CD3+ CD4+ CD45RA+ CD45RO− CD31+ RTE are reported to be TCR diverse and to contain regulatory T cells, we found it important to report that continuously reduced numbers of CD3+ CD4+ CD45RA+ CD45RO− CD31+ RTE, in the context of CHD7 haploinsufficiency and despite severe lymphopenia, is consistent with an uneventful clinical outcome. [Copyright &y& Elsevier]
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- 2013
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33. Aspects of investigating scrambling in the synthesis of porphyrins: different analytical methods
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Nielsen, Christian B. and Krebs, Frederik C.
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PORPHYRINS , *MACROCYCLIC compounds , *BIOLOGICAL pigments , *HETEROCYCLIC compounds - Abstract
Abstract: Herein, we discuss the analyses and quantification of the different components in porphyrin mixtures, prepared from p-anisaldehyde, p-tolualdehyde, and 5-(4-bromophenyl)-dipyrromethane with acid catalysis, using NMR and HPLC. The advantages and disadvantages of these analytical methods are emphasized. Due to the similar size of a bromine atom and a methyl group it was possible to grow crystals suitable for X-ray crystallographic studies from a mixture of porphyrins, where the 4-position of the meso-phenyl rings was either substituted with methyl groups or bromine atoms. We also show that X-ray studies are inferior to NMR analysis for determining the components in a porphyrin mixture. [Copyright &y& Elsevier]
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- 2005
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34. Phenology and diameter increment in seedlings of European beech (Fagus sylvatica L.) as affected by different soil water contents: variation between and within provenances.
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Nielsen, Christian Nørgård and Jørgensen, Finn Vanman
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BIOLOGICAL adaptation ,EUROPEAN beech - Abstract
The effect of different soil water levels on phenology and growth of 14 provenances of European beech (Fagus sylvatica L.) was investigated in a glasshouse experiment. The genetic variation within one provenance was further studied by including 10 half-sib families from a Danish stand in the experiment. Flushing and the time for onset of diameter growth were significantly different between provenances. Length of the growing season varied significantly among provenances and was highly affected by the soil water content. Root collar diameter increment during the experimental treatment was reduced by 43% in plants at low compared to plants at medium and high soil water content. The corresponding reduction in height was 53%. Differences between provenances and the interaction between provenances and the soil water treatments were significant for growth response. This interaction term was not significant in the material of 10 half-sib families. Linear geographic and clinal trends were revealed for growth and phenological parameters, but these relationships depended on the soil water levels. The provenances from northern Europe had a fairly homeostatic expression on a low growth level across the soil water gradient, whereas the southern provenances showed a much stronger positive response to increase in soil water content. Consequently, the south European provenances had a greater adaptability to the changing growth conditions. The genetic variation in growth response within one Danish provenance was comparable with the variation between provenance under dry soil conditions, whereas this was not the case under moist and wet soil conditions. The results indicate that a substantial gain in evolutionary adaptability is possible for north European forestry by choice of material from central and southern Europe or by mixing autochton plant material with more southern seed sources. [Copyright &y& Elsevier]
- Published
- 2003
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35. Safety of the live Escherichia coli vaccine Poulvac® E. coli in layer parent stock in a field trial.
- Author
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Christensen, Henrik and Nielsen, Christian
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ESCHERICHIA coli O157:H7 , *ESCHERICHIA coli , *VACCINES , *COLIFORMS , *AGRICULTURAL egg production , *HENS - Abstract
• The safety of the live Escherichia coli vaccine Poulvac® E. coli was tested with a flock of layer parents. • All coliform isolates collected from whole eggs and cloacal swabs were tested in parallel for growth on minimal agar and blood agar to identify the vaccine strain. • Isolates tested both with PCR and PFGE showed the wild type version of the aroA gene and different PFGE profile from the vaccine strain of Poulvac® E. coli. • The Poulvac® E. coli vaccine strain of E. coli was not identified from unbroken eggs, the content eggs or from cloacal swabs with at least 95 % probability on flock level. • The use of the vaccine is safe for hens in lay with lack of survival of the vaccine strain and lack of negative effects on the hens including egg production. The safety of the live Escherichia coli vaccine Poulvac® E. coli was tested with a flock (10,000) of layer parents aged 30 weeks. Three and 7 days after vaccination, 60 whole unbroken eggs, the egg white and yolk of 60 eggs and 60 cloacal swabs were enriched in MacConkey broth. At both sampling times, 6 out of 60 whole eggs were found positive for coliform bacteria. None of the enriched samples of yolk + egg white were positive for coliform bacteria. Three and seven days after vaccination 44 and 37, respectively out of 60 swabs were positive for coliform bacteria in MacConkey broth. All coliform isolates collected from whole eggs and cloacal swabs were tested in parallel for growth on minimal agar and blood agar to identify the vaccine strain. Some isolates showed reduced growth on minimal agar compared to blood agar and they were tested further with a PCR for the aroA gene mutation and all were found with the wild type version of the gene. Only two isolates did not grow on minimal agar but grew on blood agar and they were tested both with PCR and PFGE. They also showed the wild type version of the aroA gene and their PFGE profile was different from the vaccine strain of Poulvac® E. coli. In conclusion, the Poulvac® E. coli vaccine strain of E. coli was not identified at the detection limit of one CFU on one egg or in the content of one egg or from a cloacal swab of one hen with at least 95 % probability on flock level. The use of the vaccine is safe for hens in lay with lack of survival of the vaccine strain and lack of negative effects on the hens including egg production. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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36. Classification and enzyme kinetics of formate dehydrogenases for biomanufacturing via CO2 utilization.
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Nielsen, Christian Førgaard, Lange, Lene, and Meyer, Anne S.
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DEHYDROGENASES , *ELECTRON donors , *AMINO acid sequence , *SEQUENCE alignment , *ENZYME kinetics , *CARBON dioxide - Abstract
The reversible interconversion of formate (HCOO−) and carbon dioxide (CO 2) is catalyzed by formate dehydrogenase (FDH, EC 1.17.1.9). This enzyme can be used as a first step in the utilization of CO 2 as carbon substrate for production of high-in-demand chemicals. However, comparison and categorization of the very diverse group of FDH enzymes has received only limited attention. With specific emphasis on FDH catalyzed CO 2 reduction to HCOO−, we present a novel classification scheme for FDHs based on protein sequence alignment and gene organization analysis. We show that prokaryotic FDHs can be neatly divided into six meaningful sub-types. These sub-types are discussed in the context of overall structural composition, phylogeny of the gene segment organization, metabolic role, and catalytic properties of the enzymes. Based on the available literature, the influence of electron donor choice on the efficacy of FDH catalyzed CO 2 reduction is quantified and compared. This analysis shows that methyl viologen and hydrogen are several times more potent than NADH as electron donors. Hence, the new FDH classification scheme and the electron donor analysis provide an improved base for developing FDH-facilitated CO 2 reduction as a viable step in the utilization of CO 2 as carbon source for green production of chemicals. [ABSTRACT FROM AUTHOR]
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- 2019
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37. Rare earth (Sm/Eu/Tm) doped ZrO2 driven electro-catalysis, energy storage, and scaffolding in high-performance perovskite solar cells.
- Author
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Jaffri, Shaan Bibi, Ahmad, Khuram Shahzad, Abrahams, Isaac, Kousseff, Christina J., Nielsen, Christian B., and Almutairi, Bader O.
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HYDROGEN evolution reactions , *SAMARIUM , *RARE earth oxides , *ENERGY storage , *SOLAR cells , *ENERGY harvesting , *SOLAR energy conversion , *ZIRCONIUM oxide - Abstract
Current work presents the first report on the modification of zirconia (ZrO 2) by doping it with the lanthanides oxides i.e. [samarium, europium, and thulium] forming a [Sm/Eu/Tm] co-doped ZrO 2 system. Lanthanide doping tailored the structure of host material by causing considerable bandgap energy shrinkage from 4.04 to 3.57 eV and reduction in the crystallite size from 67.92 to 45.23 nm. Profound electro-catalytic potential was reflected analyzed via linear sweep voltammetry showing the excellent of developed catalytic towards H 2 evolution with lower overpotential i.e. 133 mV and Tafel slope of 119.3 mV dec−1. While for O 2 evolution, the electro-catalyst succeeded in gaining overpotential and Tafel slope values of 310 mV and 294.8 mV dec−1, respectively. With such values, this material has surpassed the conventional electro-catalysts and is proved to be an excellent hydrogen producing electro-catalyst. The electrical charge storage potential was analyzed for [Sm/Eu/Tm] co-doped ZrO 2 decorated nickel foam electrode for development into a super-capacitor. This electrode was impressively stable for 10 cycles after 20 days checked through cyclic voltammetry. Furthermore, an augmented specific capacitance of 447 F g−1 was achieved by the doped electrode when compared with the pristine one approaching 83.69 F g−1. The electrical energy storage capacity of [Sm/Eu/Tm] co-doped ZrO 2 is even higher than the conventionally used metal oxides. In terms of the interfacial electrode-electrolyte, electrochemical impedance spectroscopy was done expressing the excellent ionic diffusion and electrochemically active sites for [Sm/Eu/Tm] co-doped ZrO 2 electrode with minimal resistance. The developed doped system was used a spacer layer in a cesium lead halide perovskite solar cells having planar architecture. The spacer layer containing solar cell device succeeded in gaining a power conversion efficiency of 16.31% and a fill factor of 78% evaluated via photo-current measurements carried out under artificial solar irradiance. The impressively higher fill factor shows the effective passivation and scaffolding by the [Sm/Eu/Tm] co-doped ZrO 2. The associated device was also marked by negligible hysteresis. Chrono-potentiometry and chrono-amperometry expressed commendable accelerated service lives for 100 min inside an electrolyte. The lanthanide co-doped ZrO 2 is an effective material for the utilization in energy systems associated with the electro-catalysis of water, charge storage electrode for super-capacitors, and photovoltaic solar to electrical energy conversion. [Display omitted] • Using lanthanide doped ZrO 2 as an effective OER/HER catalyst. • Excellent H 2 evolution activity in cost effective and facile manner. • Exploring the charge storage potential for supercapacitor application. • Augmented solar energy harvesting via ZrO 2 scaffolding in perovskite solar cell. • Extended services life signifying suitability for commercialization. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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38. n-Type semiconductors for organic electrochemical transistor applications.
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Yu, Simiao, Kousseff, Christina J., and Nielsen, Christian B.
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N-type semiconductors , *ORGANIC semiconductors , *TRANSISTORS , *ORGANIC electronics , *BIOSENSORS - Abstract
Over the last decade, the organic electrochemical transistor (OECT) has appeared as a powerful platform for developing organic bioelectronic applications such as electronic biosensors and neuromorphic devices. The rapidly growing interest in this field has spurred the development of new active bioelectronic materials that are tailor-made to fulfil the mixed ionic-electronic conduction requirements of the OECT. While p-type (hole-transporting) organic semiconductors quickly appeared with impressive mixed conduction properties, their electron-transporting counterparts, n-type organic semiconductors have lagged severely in terms of OECT performance metrics. Here, we review recent progress on the development of n-type organic semiconductors, including both small-molecule and polymer systems, for OECT applications and discuss the bioelectronic applications that have emerged from the materials development. • Over the last couple of years, n-type semiconductors have progressed significantly in the context of mixed ionic-electronic conduction. • We review the recent literature on n-type semiconductors for bioelectronic applications covering both small-molecule and polymer systems and their OECT performance. • We give an overview of noteworthy applications that utilise these new materials and their specific properties and discuss the challenges and future directions of the field. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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39. The contact system in chronic kidney disease and hemodialysis – A cross-sectional study.
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Palarasah, Yaseelan, Borg, Rikke, Bladbjerg, Else-Marie, Pham, Stephanie Thuy Duong, Mejldal, Anna, Nielsen, Christian, Pedersen, Erik Bo, Jensen, Per Bruno, Thiesson, Helle Charlotte, and Pilely, Katrine
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CHRONIC kidney failure , *PERITONEAL dialysis , *KIDNEY physiology , *KALLIKREIN , *MOLECULAR weights - Abstract
The contact system (CAS) is a part of both the immune system and the coagulation system. The involvement of the CAS in chronic kidney disease (CKD) and hemodialysis (HD) has been documented, yet conflicting findings have hindered a comprehensive understanding. This study aimed to investigate whether CAS activation occurs in patients with chronic kidney failure undergoing HD compared with those undergoing peritoneal dialysis (PD), patients with CKD not receiving replacement therapy, or healthy controls and to assess the impact of HD on CAS from pre- to post-dialysis during a single session of HD. In this cross-sectional study, blood samples from HD patients (n = 106), PD patients (n = 40), CKD patients (n = 60), and healthy control subjects (n = 80) were analyzed. The levels of CAS components, including factor XII, prekallikrein, high-molecular-weight kininogen (HK), cleaved HK (cHK), and C1-inhibitor, and functional kallikrein generation were determined. Among HD patients, CAS measures were evaluated both pre- and post-dialysis. Linear regression models and linear mixed models were employed to analyze associations and changes. HD patients had altered levels of prekallikrein, factor XII, and cHK compared with PD patients, CKD patients, and the healthy control group. Moreover, HD patients demonstrated increased levels of C1-inhibitor and reduced functional kallikrein generation, a pattern also observed in PD patients and, to a lesser degree, in CKD patients when compared with healthy controls. Notably, no CAS activation was detected during HD. Impaired kidney function, especially in patients undergoing HD or PD, was associated with reduced functional kallikrein generation and altered levels of CAS components, implying continuous CAS activation in CKD. There was no indication of significant activation of factor XII-mediated CAS during HD. The role of CAS in CKD, independently of dialysis, should be addressed in future research. [Display omitted] • Impaired kidney function is associated with reduced functional capacity of the contact system. • The contact system is not activated during hemodialysis. • The role of the contact system in chronic kidney disease, independently of dialysis, should be addressed in future research. [ABSTRACT FROM AUTHOR]
- Published
- 2025
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- View/download PDF
40. Design of a delay-insensitive multiply-accumulate unit
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Nielsen, Christian D. and Martin, Alain J.
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- 1993
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41. A novel leukotriene D 4/E 4 antagonist, SR2640 (2-[3-(2-quinolylmethoxy)phenylamino]benzoic acid)
- Author
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Ahnfelt-Rønne, Ian, Kirstein, Dorte, and Kærgaard-Nielsen, Christian
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- 1988
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42. Environmental impacts of future low-carbon electricity systems: Detailed life cycle assessment of a Danish case study.
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Turconi, Roberto, Tonini, Davide, Nielsen, Christian F.B., Simonsen, Christian G., and Astrup, Thomas
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ENVIRONMENTAL impact analysis , *CARBON electrodes , *ELECTRICITY & the environment , *BIOMASS energy , *ELECTRICITY , *COGENERATION of electric power & heat , *INTERNATIONAL trade - Abstract
The need to reduce dependency on fossil resources and to decrease greenhouse gas (GHG) emissions is driving many countries towards the implementation of low-carbon electricity systems. In this study the environmental impact of a future (2030) possible low-carbon electricity system in Denmark was assessed and compared with the current situation (2010) and an alternative 2030 scenario using life cycle assessment (LCA). The influence on the final results of the modeling approach used for (i) electricity import, (ii) biomass resources, and (iii) the cogeneration of heat and power was discussed. The results showed that consumption of fossil resources and global warming impacts from the Danish electricity sector could be reduced significantly compared with 2010. Nevertheless, a reduction in GHG may be at the expense of other environmental impacts, such as the increased depletion of abiotic resources. Moreover, the results were very dependent upon biomass origin: when agricultural land was affected by biomass import, and land use changes and transportation were included, GHG emissions from imported biomass were comparable to those from fossil fuels. The results were significantly influenced by the modeling approach regarding the import of electricity, biomass provision, and the allocation between heat and power in cogeneration plants. As the importance of all three aspects is likely to increase in the future, transparency in LCA modeling is critical. Characterized impacts for Danish power plants in 2010 and 2030 (including corresponding electricity supply mixes) were provided, thus enabling future LCA studies to include appropriately impacts from the Danish electricity sector. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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- View/download PDF
43. Impact of UHT treatment and storage on liquid infant formula: Complex structural changes uncovered by centrifugal field-flow fractionation with multi-angle light scattering.
- Author
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Lund, Pernille, Nielsen, Søren Bang, Nielsen, Christian Fiil, Ray, Colin A., and Lund, Marianne N.
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FIELD-flow fractionation , *LIGHT scattering , *INFANT formulas , *STRUCTURAL health monitoring , *HEATING load , *LIQUIDS - Abstract
• The heat load of an UHT treatment determines storage-induced structural changes. • Field-flow fractionation can be used for characterisation of complex aggregates. • Extensive non-reducible protein material is found in liquid infant formula. • High heat load during UHT treatment leads to increased structural changes. Protein modifications in liquid infant formula (IF) have been widely studied, but distinguishing between heat- and storage-induced structural changes remains challenging. A generic liquid IF was subjected to direct or indirect UHT treatment and stored at 40 °C up to 180 days. Colour and pH were monitored and structural changes were characterised by dynamic light scattering, SDS-PAGE and centrifugal field-flow fractionation (FFF) coupled with multi-angle light scattering (MALS) and UV detectors to evaluate whether heat-induced differences would level out during storage. Both direct- and indirect UHT treatment led to structural changes, where the higher heat load of the indirect UHT treatment caused more pronounced changes. Indications were that storage-induced changes in pH, browning and non-reducible cross-links were not dependent on UHT treatment. However, FFF-MALS-UV analysis allowed characterisation of complex aggregates, where structural changes continued to be most pronounced in indirect UHT treated samples, and different storage-induced aggregation behaviour was observed. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
44. Population pharmacokinetics of ropivacaine used for local infiltration anaesthesia during primary total unilateral and simultaneous bilateral knee arthroplasty.
- Author
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Gromov, Kirill, Grassin-Delyle, Stanislas, Foss, Nicolai B., Pedersen, Lars Møller, Nielsen, Christian S., Lamy, Elodie, Troelsen, Anders, Urien, Saik, and Husted, Henrik
- Subjects
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LIQUID chromatography-mass spectrometry , *TOTAL knee replacement , *PHARMACOKINETICS , *ARTHROPLASTY , *ROPIVACAINE , *KNEE , *PAIN management , *RESEARCH , *CLINICAL trials , *RESEARCH methodology , *LOCAL anesthesia , *MEDICAL cooperation , *EVALUATION research , *COMPARATIVE studies , *POSTOPERATIVE pain , *LOCAL anesthetics , *LONGITUDINAL method - Abstract
Background: Ropivacaine is commonly used in local infiltration anaesthesia (LIA) as pain management after total knee arthroplasty (TKA). Although considered safe, no studies evaluated the pharmacokinetics of high-dose ropivacaine infiltration in simultaneous bilateral TKA.Methods: We studied 13 patients undergoing unilateral and 15 undergoing bilateral TKA. Standard LIA technique was used with ropivacaine 0.2%, 200 ml (400 mg) injected peri-articularly in each knee. Free and total plasma concentrations of ropivacaine were measured within 24 h using liquid chromatography-mass spectrometry. A population pharmacokinetic model was built using non-linear mixed-effects models.Results: Peak free ropivacaine concentration was 0.030 (0.017-0.071) μg ml-1 (mean [99% confidence interval]) vs 0.095 (0.047-0.208) μg ml-1, and peak total ropivacaine concentration was 0.756 (0.065-1.222) μg ml-1vs 1.695 (0.077-3.005) μg ml-1 for unilateral and bilateral TKA, respectively. The pharmacokinetics was ascribed a one-compartment model with first-order absorption. The main identified covariates were protein binding, allometrically scaled body weight on clearance and volume, and unilateral or bilateral surgery on volume.Conclusions: This is the first study to investigate the pharmacokinetics of free and total ropivacaine after unilateral and bilateral TKA. A population model was successfully built and peak free ropivacaine concentration stayed below previously proposed toxic thresholds in patients undergoing unilateral and bilateral TKA receiving LIA with high-dose ropivacaine.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04702282. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
45. Quantum modelling of multi-directional fused-ring electron acceptors for organic photovoltaics.
- Author
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Abid, Zeeshan, Ali, Liaqat, Shahid, Munazza, Nielsen, Christian B., Altaf, Muhammad, Min, Jie, and Ashraf, Raja Shahid
- Subjects
- *
ELECTROPHILES , *FRONTIER orbitals , *BAND gaps , *DENSITY functional theory , *PHOTOVOLTAIC power generation , *ELECTRON donors - Abstract
Multi-directional fused-ring electron acceptors (FREAs) feature a fused-ring backbone that extends in multiple directions through bridging and acceptor units. This unique structural design imparts several advantageous properties, like increased light absorption, precise energy level adjustments, improved electron mobility, reduced energy loss, and enhanced efficiency in organic photovoltaic (OPV) devices. In this study, we designed seven novel multi-directional FREAs and conducted a comprehensive computational analysis using Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT). The designed molecules feature a benzotrithienopyrrole central core connected to a π-bridge acceptor, either benzothiadiazole or benzotriazole, and three varying terminal acceptors, including malononitrile, 2-(5,6-difluoro-3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile, and 2-(3-methyl-4-oxothiazolidin-2-ylidene)malononitrile. Our investigation encompassed the evaluation of geometry, frontier molecular orbitals (FMOs), optical properties, density of states (DOS), charge mobilities, dipole moment, global reactivity descriptors, molecular electrostatic potential (MEP), transition density matrix (TDM), and OPV device-related parameters. The results revealed significant potential of the designed molecules as FREAs for OPVs, thus highlighting their suitability for further experimental exploration. [Display omitted] • New multi-directional fused-ring electron acceptors show enhanced organic photovoltaic device properties. • Simplifying the core and incorporating π-bridge and terminal acceptors rivals or surpasses performance of existing designs. • Quantum modeling shows improved conjugation, reduced band gaps, orbitals degeneracy and improved optoelectronic properties. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing.
- Author
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Danielsen, E. Thomas, Moeller, Morten E., Yamanaka, Naoki, Ou, Qiuxiang, Laursen, Janne M., Soenderholm, Caecilie, Zhuo, Ran, Phelps, Brian, Tang, Kevin, Zeng, Jie, Kondo, Shu, Nielsen, Christian H., Harvald, Eva B., Faergeman, Nils J., Haley, Macy J., O'Connor, Kyle A., King-Jones, Kirst, O'Connor, Michael B., and Rewitz, Kim F.
- Subjects
- *
DROSOPHILA melanogaster , *STEROID hormones , *GENE expression , *DROSOPHILA genetics , *DEVELOPMENTAL biology - Abstract
Summary Steroid hormones control important developmental processes and are linked to many diseases. To systematically identify genes and pathways required for steroid production, we performed a Drosophila genome-wide in vivo RNAi screen and identified 1,906 genes with potential roles in steroidogenesis and developmental timing. Here, we use our screen as a resource to identify mechanisms regulating intracellular levels of cholesterol, a substrate for steroidogenesis. We identify a conserved fatty acid elongase that underlies a mechanism that adjusts cholesterol trafficking and steroidogenesis with nutrition and developmental programs. In addition, we demonstrate the existence of an autophagosomal cholesterol mobilization mechanism and show that activation of this system rescues Niemann-Pick type C1 deficiency that causes a disorder characterized by cholesterol accumulation. These cholesterol-trafficking mechanisms are regulated by TOR and feedback signaling that couples steroidogenesis with growth and ensures proper maturation timing. These results reveal genes regulating steroidogenesis during development that likely modulate disease mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
47. A Formylated Hexapeptide Ligand Mimics the Ability of Wnt-5a to Impair Migration of Human Breast Epithelial Cells.
- Author
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Säfholm, Annette, Leandersson, Karin, Dejmek, Janna, Nielsen, Christian Kamp, Villoutreix, Bruno O., and Andersson, Tommy
- Subjects
- *
PROTEINS , *CANCER patients , *BREAST cancer , *CELL adhesion , *EPITHELIAL cells , *CELL lines , *AMINO acids - Abstract
Loss of Wnt-5a protein expression is associated with shorter recurrence-free survival in breast carcinoma patients and increased motility in mammary cell lines. Based on sequence analysis of Wnt-5a, we identified 14 peptide fragments and investigated their ability to mimic the effects of Wnt-Sa on mammary cell adhesion and migration. Two of these peptides significantly increased adhesion and impaired migration in the non-tumorigenic HB2 breast epithelial cell line and in the MDA-MB-468 breast cancer cell line, both of which show little endogenous expression of the Wnt-5a protein. We removed two amino acids at a time from the N terminus of the shorter of these two peptides to identify the shortest peptide that still inhibited migration. The influence on tumor cell adhesion was gradually lost and was no longer detectable when only six amino acids remained. However, formylation of the N-terminal methionine of this hexapeptide restored its effect on adhesion and reduced tumor cell motility via a Frizzled-5 receptor-dependent mechanism, even at a low pH such as encountered in breast tumor tissue. This formylated hexapeptide ligand induced a rapid cytosolic calcium signal, whereas it did not affect the cellular levels of unphosphorylated β-catenin or active INK. The novel formyl-Met-Asp-Gly-Cys-Glu-Leu peptide ligand is not only a valuable experimental tool hut has also a potential role in antimetastatic treatment of the 50% of human breast cancer patients that have reduced endogenous Wnt-5a protein expression. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
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