| 1. |
- Huertas-Hernando, D., et al.
(författare)
-
Hydro power flexibility for power systems with variable renewable energy sources : An IEA Task 25 collaboration
- 2016
-
Ingår i: Wiley Interdisciplinary Reviews. - : John Wiley & Sons. - 2041-8396 .- 2041-840X.
-
Tidskriftsartikel (refereegranskat)abstract
- Hydro power is one of the most flexible sources of electricity production. Power systems with considerable amounts of flexible hydro power potentially offer easier integration of variable generation, e.g., wind and solar. However, there exist operational constraints to ensure mid-/long-term security of supply while keeping river flows and reservoirs levels within permitted limits. In order to properly assess the effective available hydro power flexibility and its value for storage, a detailed assessment of hydro power is essential. Due to the inherent uncertainty of the weather-dependent hydrological cycle, regulation constraints on the hydro system, and uncertainty of internal load as well as variable generation (wind and solar), this assessment is complex. Hence, it requires proper modeling of all the underlying interactions between hydro power and the power system, with a large share of other variable renewables. A summary of existing experience of wind integration in hydro-dominated power systems clearly points to strict simulation methodologies. Recommendations include requirements for techno-economic models to correctly assess strategies for hydro power and pumped storage dispatch. These models are based not only on seasonal water inflow variations but also on variable generation, and all these are in time horizons from very short term up to multiple years, depending on the studied system. Another important recommendation is to include a geographically detailed description of hydro power systems, rivers' flows, and reservoirs as well as grid topology and congestion.
|
|
| 2. |
- Ding, Haozhong, et al.
(författare)
-
Incorporation of a Hydrophilic Spacer Reduces Hepatic Uptake of HER2-Targeting Affibody-DM1 Drug Conjugates
- 2019
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 11:8
-
Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules are small affinity-engineered scaffold proteins which can be engineered to bind to desired targets. The therapeutic potential of using an affibody molecule targeting HER2, fused to an albumin-binding domain (ABD) and conjugated with the cytotoxic maytansine derivate MC-DM1 (AffiDC), has been validated. Biodistribution studies in mice revealed an elevated hepatic uptake of the AffiDC, but histopathological examination of livers showed no major signs of toxicity. However, previous clinical experience with antibody drug conjugates have revealed a moderateto high-grade hepatotoxicity in treated patients, which merits efforts to also minimize hepatic uptake of the AffiDCs. In this study, the aim was to reduce the hepatic uptake of AffiDCs and optimize their in vivo targeting properties. We have investigated if incorporation of hydrophilic glutamate-based spacers adjacent to MC-DM1 in the AffiDC, (Z(HER2:2891))(2) -ABD-MC-DM1, would counteract the hydrophobic nature of MC-DM1 and, hence, reduce hepatic uptake. Two new AffiDCs including either a triglutamate-spacer-, (Z(HER2:2891))(2)-ABD-E-3-MC-DM1, or a hexaglutamate-spacer-, (Z(HER2:2891))(2)-ABD-E-6-MC-DM1 next to the site of MC-DM1 conjugation were designed. We radiolabeled the hydrophilized AffiDCs and compared them, both in vitro and in vivo, with the previously investigated (Z(HER2:2891))(2)-ABD-MC-DM1 drug conjugate containing no glutamate spacer. All three AffiDCs demonstrated specific binding to HER2 and comparable in vitro cytotoxicity. A comparative biodistribution study of the three radiolabeled AffiDCs showed that the addition of glutamates reduced drug accumulation in the liver while preserving the tumor uptake. These results confirmed the relation between DM1 hydrophobicity and liver accumulation. We believe that the drug development approach described here may also be useful for other affinity protein-based drug conjugates to further improve their in vivo properties and facilitate their clinical translatability.
|
|
| 3. |
- Junttila, Sofia, et al.
(författare)
-
Upscaling Northern Peatland CO2 Fluxes Using Satellite Remote Sensing Data
- 2021
-
Ingår i: Remote Sensing. - : MDPI AG. - 2072-4292. ; 13:4
-
Tidskriftsartikel (refereegranskat)abstract
- Peatlands play an important role in the global carbon cycle as they contain a large soil carbon stock. However, current climate change could potentially shift peatlands from being carbon sinks to carbon sources. Remote sensing methods provide an opportunity to monitor carbon dioxide (CO2) exchange in peatland ecosystems at large scales under these changing conditions. In this study, we developed empirical models of the CO2 balance (net ecosystem exchange, NEE), gross primary production (GPP), and ecosystem respiration (ER) that could be used for upscaling CO2 fluxes with remotely sensed data. Two to three years of eddy covariance (EC) data from five peatlands in Sweden and Finland were compared to modelled NEE, GPP and ER based on vegetation indices from 10 m resolution Sentinel-2 MSI and land surface temperature from 1 km resolution MODIS data. To ensure a precise match between the EC data and the Sentinel-2 observations, a footprint model was applied to derive footprint-weighted daily means of the vegetation indices. Average model parameters for all sites were acquired with a leave-one-out-cross-validation procedure. Both the GPP and the ER models gave high agreement with the EC-derived fluxes (R-2 = 0.70 and 0.56, NRMSE = 14% and 15%, respectively). The performance of the NEE model was weaker (average R-2 = 0.36 and NRMSE = 13%). Our findings demonstrate that using optical and thermal satellite sensor data is a feasible method for upscaling the GPP and ER of northern boreal peatlands, although further studies are needed to investigate the sources of the unexplained spatial and temporal variation of the CO2 fluxes.
|
|
| 4. |
- Zhang, Jie, et al.
(författare)
-
Pre-clinical Evaluation of Drug Conjugates Based on Affibody Molecules Targeting HER3-Expressing Tumors
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The outcome of clinical trials evaluating drugs targeting the human epidermal growth factor receptor 3 (HER3) has been poor, with primary concerns related to lack of efficacy. The development of novel modalities that have the potential to improve the efficacy of HER3-targeting drugs is therefore warranted. Here, we have investigated the in vitro and in vivo properties of affibody-based drug conjugates targeting HER3. The HER3- targeting affibody molecule ZHER3 was fused in a mono- and bivalent format to an albumin binding domain (ABD) for in vivo half-life extension and was coupled to the cytotoxic drug DM1 via a non-cleavable maleimidocaproyl (mc) linker. The bivalent drug conjugate, ZHER3-ABD-ZHER3-mcDM1, demonstrated 10-fold higher toxicity to the HER3-expressing human cell line BxPC3 compared to the monovalent drug conjugate ZHER3-ABD-mcDM1. In vivo, a moderate uptake was recorded for [99mTc]Tc-labeled ZHER3-ABD-ZHER3-mcDM1 in BxPC3-derived tumors (3.5 ± 0.3%IA/g) at 24 h after injection, and clearance was predominately renal-mediated. Treatment of mice with implanted BxPC3 pancreatic human tumors showed that a combination of ZHER3-ABD-ZHER3-mcDM1 and its non-toxic analog ZHER3-ABD-ZHER3 was superior to a treatment scheme including only ZHER3-ABD- ZHER3, providing tumor growth inhibition and longer median survival of the mice (90 d) in comparison to the monotherapy (68 d) and vehicle control (49 d). In conclusion, the bivalent drug conjugate ZHER3-ABD-ZHER3-mcDM1 produced the strongest cytotoxic effect on HER3-expressing BxPC3 cells compared to previously investigated constructs, including non-toxic ZHER3-ABD-ZHER3 and the monovalent drug conjugate ZHER3-ABD- mcDM1, without apparent toxicity in vivo.
|
|
