| 1. |
- Abramson, Alex, et al.
(författare)
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Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 40:1, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- Oral administration provides a simple and non-invasive approach for drug delivery. However, due to poor absorption and swift enzymatic degradation in the gastrointestinal tract, a wide range of molecules must be parenterally injected to attain required doses and pharmacokinetics. Here we present an orally dosed liquid auto-injector capable of delivering up to 4-mg doses of a bioavailable drug with the rapid pharmacokinetics of an injection, reaching an absolute bioavailability of up to 80% and a maximum plasma drug concentration within 30 min after dosing. This approach improves dosing efficiencies and pharmacokinetics an order of magnitude over our previously designed injector capsules and up to two orders of magnitude over clinically available and preclinical chemical permeation enhancement technologies. We administered the capsules to swine for delivery of clinically relevant doses of four commonly injected medications, including adalimumab, a GLP-1 analog, recombinant human insulin and epinephrine. These multi-day dosing experiments and oral administration in awake animal models support the translational potential of the system.
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| 2. |
- Borel, Cédric, 1979, et al.
(författare)
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Family of Isoreticular Chiral Metal-Organic Frameworks Based on Coordination and Hydrogen Bonds in [M[Co(ethylenediamine)(oxalato)2]2]
- 2010
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 10:4, s. 1971-1978
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Tidskriftsartikel (refereegranskat)abstract
- From the parent compound [Ca[Co(ethylenediamine)(oxalato)2]2]n . 4H2O, 1, a series of framework compounds was prepared via the soluble sodium salt and crystal growth with the divalent metal ions Cd2+, Mn2+, and Sr2+, (2-4). These compounds have the same general formula [M[Co(ethylenediamine)(oxalato)2]2]n . xH2O, and they all form the same four- and eight-connected 3D net having scu topology (and are thus isoreticular) with water filled channels of variable size running in one direction of the crystals. However, they crystallize in two different space groups, the chiral P21) (3, 4, and the low temperature form of 1) and the noncentrosymmetric P-4 (1 and 2). The potential voids upon water removal are 18-20% of the unit cell. Preliminary gas sorption measurements at 298 K and 8 bar show substantial CO2 and N2O uptake (12-14% and 15-16% by mass, respectively), while the H2 uptake was 0.18%, a relatively high value considering the low pressure and high temperature.
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| 3. |
- Clark, Douglas S., et al.
(författare)
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Klaus Mosbach Tribute
- 2015
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 1097-0290 .- 0006-3592. ; 112:4, s. 645-647
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Dengler, Juergen, et al.
(författare)
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GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands
- 2018
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Ingår i: Phytocoenologia. - : Schweizerbart. - 0340-269X. ; 48:3, s. 331-347
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Tidskriftsartikel (refereegranskat)abstract
- GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
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| 5. |
- Langer, Claus Oliver
(författare)
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Catecholaminergic neurotransmission in heart and brain : development of tracers for positron emission tomography
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The catecholamines norepinephrine and its biosynthetic precursor dopamine are two principal neurotransmitters in the human central nervous system (CNS). Moreover, norepinephrine is a major transmitter substance in the peripheral, autonomic nervous system. Positron emission tomography (PET) is a non-invasive imaging technique that uses positron-labeled molecules to image and measure the function of biological processes in vivo. Neuronal catecholaminergic pathways, both in CNS and periphery, are involved in various disease conditions and form important targets for therapeutic agents. Different elements of synaptic neurotransmission can be targeted for molecular imaging with PET. This doctoral thesis exemplifies two strategies in the development of a catecholaminergic PET tracer. First, radiolabeled analogues of the false adrenergic neurotransmitter metaraminol (MR) were synthesized as potential PET tracers to assess presynaptic adrenergic nerve function in the heart. Due to the considerable vasopressor activity of the parent molecule the achievement of high specific radioactivity (SR) was of central interest. MR was labeled in 4- and 6-position of the aromatic ring with no-carrier-added 76Br or 18F. Whereas the first approach afforded tracers without neuronal affinity, the 18F-labeled compounds localized avidly and specifically within adrenergic neurons. Due to higher radiochemical yields for 4-substitution, 4-[18F]fluorometaraminol appeared to be the preferred tracer for cardiac neuronal imaging, Second, new radioligands to map dopamine D2-like receptors in the brain were prepared and characterized. These include the high-affinity benzamide [11C]epidepride, which is suitable for the delineation of lowdensity extrastriatal dopamine D2 receptors. In addition, the novel D4 ligand PB-12 was labeled with 11C, but failed to visualize the dopamine D4 receptor in monkey brain. Moreover, available procedures for radiolabeling of the benzamide ligands [11C]raclopride and [11C]FLB 457 were optimized. For the synthesis of [11C]raclopride the recently developed methylating agent [11C]methyl triflate was employed as a more reactive alternative to [11C]methyl iodide. For [11C]FLB 457 the SR was improved by more than 50% compared to the standard approach by using a new gas-phase method for the preparation of [11C]methyl iodide. High SR is of particular importance for ligands like [11C]FLB 457 that are used to map low-density receptor populations.
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| 6. |
- Langer, Dominik, et al.
(författare)
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HelioScan : A software framework for controlling in vivo microscopy setups with high hardware flexibility, functional diversity and extendibility
- 2013
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Ingår i: Journal of Neuroscience Methods. - : Elsevier BV. - 0165-0270 .- 1872-678X. ; 215:1, s. 38-52
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Tidskriftsartikel (refereegranskat)abstract
- Intravital microscopy such as in vivo imaging of brain dynamics is often performed with custom-built microscope setups controlled by custom-written software to meet specific requirements. Continuous technological advancement in the field has created a need for new control software that is flexible enough to support the biological researcher with innovative imaging techniques and provide the developer with a solid platform for quickly and easily implementing new extensions. Here, we introduce HelioScan, a software package written in LabVIEW, as a platform serving this dual role. HelioScan is designed as a collection of components that can be flexibly assembled into microscope control software tailored to the particular hardware and functionality requirements. Moreover, HelioScan provides a software framework, within which new functionality can be implemented in a quick and structured manner. A specific HelioScan application assembles at run-time from individual software components, based on user-definable configuration files. Due to its component-based architecture, HelioScan can exploit synergies of multiple developers working in parallel on different components in a community effort. We exemplify the capabilities and versatility of HelioScan by demonstrating several in vivo brain imaging modes, including camera-based intrinsic optical signal imaging for functional mapping of cortical areas, standard two-photon laser-scanning microscopy using galvanometric mirrors, and high-speed in vivo two-photon calcium imaging using either acousto-optic deflectors or a resonant scanner. We recommend HelioScan as a convenient software framework for the in vivo imaging community.
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| 7. |
- Lygnerud, Kristina, et al.
(författare)
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Handbook for increased recovery of urban excess heat
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this book is to consolidate information from low temperature waste heat recovery demonstration sites. Apart from technical validation, the ReUseHeat project has generated knowledge about the urban waste heat potential in Europe, main stakeholders and different business aspects. Five stakeholder groups are targeted. These are urban waste heat owners, District Heating (DH) companies, policy makers, investors and customers. In the first chapter of the book, the concept of urban waste heat is introduced and the urban waste heat potential in Europe is presented. Thereafter (chapter two), information on business aspects is provided (stakeholders, value chain, risks, contracts and business model characteristics). Chapter three showcases the demonstrator concepts (waste heat recovery from data centre, hospital, metro and awareness creation about urban waste heat recovery) and performance data. Throughout the writing of the handbook, it was identified that it is important to compare the cost of different heating alternatives, to facilitate customer decision making. Therefore, a model was derived to compare costs of heating alternatives. It is presented in chapter four. Urban waste heat recovery is news. It is therefore important that stakeholders are made aware of the possibility to use the locally available heat and to start collaborating in new ways. To ensure as much stakeholder engagement as possible, the writing process of this book encompassed a six-month stakeholder involvement process. The stakeholder input is presented in chapter five. In chapter six, thoughts on the future development of district energy, policy implications and major learnings from the project are presented. This book was written within the ReUseHeat project. The work on the book was initiated after the first out of five years of activity to ensure that the consortium would be engaged in its development and to capture the knowledge generated on an ongoing basis. The final version of the book was ready and placed on the ReUseHeat webpage in September 2022. The project webpage remains in operation until 2024. The book not only exists in digital format. 600 copies were also printed and distributed to relevant stakeholders. All partners of the consortium have contributed to the writing of the book.
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| 8. |
- Mahmoudkhani, Amir H., et al.
(författare)
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Radical Additions of Bis(trimethylsilyl)phosphite to Vinyltrimethylsilane and Vinyltriethoxysilane: Crystal Structure of 2-Trimethylsilylethylphosphonic Acid
- 2003
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Ingår i: Phosphorus, Sulfur and Silicon and the Related Elements. - : Informa UK Limited. - 1042-6507 .- 1563-5325. ; 178:10, s. 2159-2168
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Tidskriftsartikel (refereegranskat)abstract
- Organosilicon-phosphonate compounds with the general formula (R)n(RO)3mnSi(CH2)mP(O)(OSiR'3)2 are designed for application as novel materials for surface treatments and modifications. A solvothermal method based on the reaction of bis(trimethylsilyl)phosphite with vinyltrimethylsilane and vinyltriethoxysilane in the presence of a peroxide in benzene solvent was used to synthesize the silyl-substituted esters of organosilicon-phosphonate compounds. 2-Trimethylsilylethanephosphonic acid was prepared from its bis(trimethylsilyl) ester by alcoholysis. The crystal structure of the acid consists of two-dimensional arrays built up from the (P--)O--H···O--P hydrogen bonds.
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| 9. |
- Müllauer, Julia, et al.
(författare)
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Pharmacokinetic modeling of P-glycoprotein function at the rat and human blood--brain barriers studied with (R)-[11C]verapamil positron emission tomography.
- 2012
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Ingår i: EJNMMI Research. - 2191-219X. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: This study investigated the influence of P-glycoprotein (P-gp) inhibitor tariquidar on the pharmacokinetics of P-gp substrate radiotracer (R)-[11C]verapamil in plasma and brain of rats and humans by means of positron emission tomography (PET). METHODS: Data obtained from a preclinical and clinical study, in which paired (R)-[11C]verapamil PET scans were performed before, during, and after tariquidar administration, were analyzed using nonlinear mixed effects (NLME) modeling. Administration of tariquidar was included as a covariate on the influx and efflux parameters (Qin and Qout) in order to investigate if tariquidar increased influx or decreased outflux of radiotracer across the blood--brain barrier (BBB). Additionally, the influence of pilocarpine-induced status epilepticus (SE) was tested on all model parameters, and the brain-to-plasma partition coefficient (VT-NLME) was calculated. RESULTS: Our model indicated that tariquidar enhances brain uptake of (R)-[11C]verapamil by decreasing Qout. The reduction in Qout in rats during and immediately after tariquidar administration (sevenfold) was more pronounced than in the second PET scan acquired 2 h after tariquidar administration (fivefold). The effect of tariquidar on Qout in humans was apparent during and immediately after tariquidar administration (twofold reduction in Qout) but was negligible in the second PET scan. SE was found to influence the pharmacological volume of distribution of the central brain compartment Vbr1. Tariquidar treatment lead to an increase in VT-NLME, and pilocarpine-induced SE lead to increased (R)-[11C]verapamil distribution to the peripheral brain compartment. CONCLUSIONS: Using NLME modeling, we were able to provide mechanistic insight into the effects of tariquidar and SE on (R)-[11C]verapamil transport across the BBB in control and 48 h post SE rats as well as in humans.
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| 10. |
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