| 1. |
- Gad, Helge, et al.
(författare)
-
MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
-
Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Hassel, Ivon, et al.
(författare)
-
The single cube apparatus for shear testing : Full-field strain data and finite element analysis of wood in transverse shear
- 2009
-
Ingår i: Composites Science And Technology. - : Elsevier BV. - 0266-3538 .- 1879-1050. ; 69:7-8, s. 877-882
-
Tidskriftsartikel (refereegranskat)abstract
- The design and analysis of wood structures require accurate data for shear properties, where transverse shear in particular has been neglected in the past. The single cube apparatus (SCA) was applied to transverse shear of Norway spruce (Picea Abies), due to the importance of this species in wood structures, such as glulam, and also its allegedly low value of GRT . Full-field strain data and FEA were used to analyze the potential of the method. The presence of a large central region of homogeneous and close to pure shear strain was confirmed. The SCA method is therefore a strong candidate for improved shear test procedures in wood and other materials, where porosity (gripping problems), heterogeneity on mm-scale and polar orthotropy (annual ring curvature) may cause particular difficulties. In contrast to many other shear test studies, the accuracy of the present GRT data is supported by documented large and homogeneous specimen stress- and strain-fields in almost pure shear, direct measurements of strain field, and careful stress analysis based on FEA.
|
|
| 5. |
- Karim, Zoheb, et al.
(författare)
-
Forming a cellulose based nanopaper using XPM
- 2017
-
Ingår i: International Conference on Nanotechnology for Renewable Materials 2017. - : TAPPI Press. - 9781510850897 ; , s. 399-407
-
Konferensbidrag (refereegranskat)
|
|
| 6. |
- Larsson, Per A., 1980-, et al.
(författare)
-
Towards optimised size distribution in commercial microfibrillated cellulose : a fractionation approach
- 2019
-
Ingår i: Cellulose. - : Springer. - 0969-0239 .- 1572-882X. ; 26:3, s. 1565-1575
-
Tidskriftsartikel (refereegranskat)abstract
- For the successful commercialisation of microfibrillated cellulose (MFC) it is of utmost importance to carefully characterise the constituent cellulose particles. This could for instance lead to the development of MFC grades with size distributions tailored for specific applications. Characterization of MFC is challenging due to the heterogeneous chemical and structural nature of MFC. This study describes a fractionation approach that combines two steps of physical sieving of larger particles and a final centrifugation step to separate out the smallest, colloidally stable particles, resulting in four distinctly different size fractions. The properties, such as size and charge, of each fraction were studied, as well as MFC filtration time, film formation, and film properties (mechanical and optical). It was found that virtually all surface charges, determined by polyelectrolyte adsorption, are located in the colloidally stable fraction of the MFC. In addition, the amount of available surface charges can be used as an estimate of the degree of fibrillation of the MFC. The partly fibrillated particles frequently displayed a branching, fringed morphology. Mechanical testing of films from the different fractions revealed that the removal of large particles may be more important for strength than achieving full fibrillation. Overall, this study demonstrates that by controlling the size distribution in MFC grades, property profiles including dewatering time to make films by filtration, rheology, film strength and optical transmittance could be optimised. [GRAPHICS] .
|
|
| 7. |
|
|
| 8. |
- Zelaya Blandon, Elmer, et al.
(författare)
-
Breaking the cycles of poverty : Strategies, achievements, and lessons learned in Los Cuatro Santos, Nicaragua, 1990-2014
- 2017
-
Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In a post-war frontier area in north-western Nicaragua that was severely hit by Hurricane Mitch in 1998, local stakeholders embarked on and facilitated multi-dimensional development initiatives to break the cycles of poverty. Objective: The aim of this paper is to describe the process of priority-setting, and the strategies, guiding principles, activities, achievements, and lessons learned in these local development efforts from 1990 to 2014 in the Cuatro Santos area, Nicaragua. Methods: Data were derived from project records and a Health and Demographic Surveillance System that was initiated in 2004. The area had 25,893 inhabitants living in 5,966 households in 2014. Results: A participatory process with local stakeholders and community representatives resulted in a long-term strategic plan. Guiding principles were local ownership, political reconciliation, consensus decision-making, social and gender equity, an environmental and public health perspective, and sustainability. Local data were used in workshops with communities to re-prioritise and formulate new goals. The interventions included water and sanitation, house construction, microcredits, environmental protection, school breakfasts, technical training, university scholarships, home gardening, breastfeeding promotion, and maternity waiting homes. During the last decade, the proportion of individuals living in poverty was reduced from 79 to 47%. Primary school enrolment increased from 70 to 98% after the start of the school breakfast program. Under-five mortality was around 50 per 1,000 live births in 1990 and again peaked after Hurricane Mitch and was approaching 20 per 1,000 in 2014. Several of the interventions have been scaled up as national programs. Conclusions: The lessons learned from the Cuatro Santos initiative underline the importance of a bottom- up approach and local ownership of the development process, the value of local data for monitoring and evaluation, and the need for multi-dimensional local interventions to break the cycles of poverty and gain better health and welfare.
|
|
| 9. |
- Andrieux, Sebastien, et al.
(författare)
-
Monodisperse highly ordered chitosan/cellulose nanocomposite foams
- 2019
-
Ingår i: Composites. Part A, Applied science and manufacturing. - : ELSEVIER SCI LTD. - 1359-835X .- 1878-5840. ; 125
-
Tidskriftsartikel (refereegranskat)abstract
- In solid foams, most physical properties are determined by the pore size and shape distributions and the organisation of the pores. For this reason, it is important to control the structure of porous materials. We recently tackled this issue with the help of microfluidic-aided foam templating, which allowed us to generate mono-disperse and highly ordered chitosan foams. However, the properties of foams also depend on the properties of the pore wall constituents. In case of chitosan-based foams, the foams have poor absolute mechanical properties, simply due to the fact that the solubility of chitosan in water is very low, so that the relative density of the freeze-dried foams becomes very small. Drawing inspiration from the field of nanocomposites, we incorporated cellulose nanofibres into the foamed chitosan solutions, with a view to strengthening the pore walls in the foam and thus the mechanical properties of the final foam. We report here how the cellulose nanofibres affect the structure of both the liquid foam template and the solid foam. The resulting nanocomposite foams have improved mechanical properties, which, however, are not proportional to the amount of cellulose nanofibres in the composites. One reason for this observation is the disturbance of the porous structure of the solid foams by the cellulose nanofibres.
|
|
| 10. |
- Ansari, Farhan, et al.
(författare)
-
Cellulose nanocomposites - Controlling dispersion and material properties through nanocellulose surface modification
- 2015
-
Ingår i: 20th International Conference on Composite Materials, ICCM 2015. - : International Committee on Composite Materials.
-
Konferensbidrag (refereegranskat)abstract
- The use of cellulosic nanofibers as reinforcement in polymer composites offers great advantages over their petroleum counterparts. Apart from being strong, stiff and low density; they are obtained from naturally occurring resources and as such are favorable from an environmental point of view. A major problem while studying nanomaterials is their tendency to agglomerate, thus leading to inhomogeneous distribution within the polymer matrix. This often results in stress concentrations in the matrix rich regions when the material is subjected to load and therefore, limits the potential application of these materials. A common approach to circumvent this is by surface modification, which facilitates the dispersion in non-polar matrices. An environmental friendly approach, inspired by clay chemistry, was used to functionalize the CNC surface. It was shown that the CNC could be modified in a rather convenient way to attach a variety of functional groups on the surface. Primarily, the problem of cellulose nanocrystal (CNC) distribution in a hydrophobic polymer matrix is investigated. Composites prepared from modified CNC were studied and compared with unmodified CNC. The distribution of the CNC is carefully monitored at different stages via UV-Vis spectroscopy and scanning electron microscopy (SEM). The mechanical properties of the resulting materials were characterized by dynamic mechanical as well as uniaxial tensile tests. It was shown that a homogeneous distribution of the CNC exposes a tremendous amount of surface area to interact with the matrix. In such a case, the stress transfer is much more efficient and perhaps, the matrix behavior is modified, which leads to significant improvements in the mechanical properties.
|
|
