| 1. |
- Alinezhad, Saeid, et al.
(författare)
-
Validation of novel biomarkers for prostate cancer progression by the combination of bioinformatics, clinical and functional studies
- 2016
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
-
Tidskriftsartikel (refereegranskat)abstract
- The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest and cytotoxicity, particularly in 3D organotypic cell culture conditions. In addition, silencing of PLA2G7, RHOU, ACSM1, LAMB1 and CACNA1D also resulted in reduced tumor cell invasion in PC3 organoid cultures. For PLA2G7 and RHOU, the effects of siRNA silencing on proliferation and cell-motility could also be confirmed in 2D monolayer cultures. In conclusion, DLX1 and RHOU showed the strongest potential as useful clinical biomarkers for PCa diagnosis, further validated by their functional roles in PCa progression. These candidates may be useful for more reliable identification of relapses or therapy failures prior to the recurrence local or distant metastases.
|
|
| 2. |
- Delekta, Szymon Sollami, et al.
(författare)
-
Fully inkjet printed ultrathin microsupercapacitors based on graphene electrodes and a nano-graphene oxide electrolyte
- 2019
-
Ingår i: Nanoscale. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 11:21, s. 10172-10177
-
Tidskriftsartikel (refereegranskat)abstract
- The advance of miniaturized and low-power electronics has a striking impact on the development of energy storage devices with constantly tougher constraints in terms of form factor and performance. Microsupercapacitors (MSCs) are considered a potential solution to this problem, thanks to their compact device structure. Great efforts have been made to maximize their performance with new materials like graphene and to minimize their production cost with scalable fabrication processes. In this regard, we developed a full inkjet printing process for the production of all-graphene microsupercapacitors with electrodes based on electrochemically exfoliated graphene and an ultrathin solid-state electrolyte based on nano-graphene oxide. The devices exploit the high ionic conductivity of nano-graphene oxide coupled with the high electrical conductivity of graphene films, yielding areal capacitances of up to 313 mu F cm-2 at 5 mV s-1 and high power densities of up to 4 mW cm-3 with an overall device thickness of only 1 mu m.
|
|
| 3. |
- Launonen, Antti P., et al.
(författare)
-
Operative versus non-operative treatment for 2-part proximal humerus fracture : A multicenter randomized controlled trial
- 2019
-
Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:7
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlthough increasingly used, the benefit of surgical treatment of displaced 2-part proximal humerus fractures has not been proven. This trial evaluates the clinical effectiveness of surgery with locking plate compared with non-operative treatment for these fractures.Methods and findingsThe NITEP group conducted a superiority, assessor-blinded, multicenter randomized trial in 6 hospitals in Finland, Estonia, Sweden, and Denmark. Eighty-eight patients aged 60 years or older with displaced (more than 1 cm or 45 degrees) 2-part surgical or anatomical neck proximal humerus fracture were randomly assigned in a 1:1 ratio to undergo either operative treatment with a locking plate or non-operative treatment. The mean age of patients was 72 years in the non-operative group and 73 years in the operative group, with a female sex distribution of 95% and 87%, respectively. Patients were recruited between February 2011 and April 2016. The primary outcome measure was Disabilities of Arm, Shoulder, and Hand (DASH) score at 2-year follow-up. Secondary outcomes included Constant–Murley score, the visual analogue scale for pain, the quality of life questionnaire 15D, EuroQol Group’s 5-dimension self-reported questionnaire EQ-5D, the Oxford Shoulder Score, and complications. The mean DASH score (0 best, 100 worst) at 2 years was 18.5 points for the operative treatment group and 17.4 points for the non-operative group (mean difference 1.1 [95% CI −7.8 to 9.4], p = 0.81). At 2 years, there were no statistically or clinically significant between-group differences in any of the outcome measures. All 3 complications resulting in secondary surgery occurred in the operative group. The lack of blinding in patient-reported outcome assessment is a limitation of the study. Our assessor physiotherapists were, however, blinded.ConclusionsThis trial found no significant difference in clinical outcomes at 2 years between surgery and non-operative treatment in patients 60 years of age or older with displaced 2-part fractures of the proximal humerus. These results suggest that the current practice of performing surgery on the majority of displaced proximal 2-part fractures of the humerus in older adults may not be beneficial.
|
|
| 4. |
- Li, Yanling, 1990, et al.
(författare)
-
Evaluation of temperature controlled oedometer test apparatus
- 2016
-
Ingår i: Energy Geotechnics. - : CRC Press. - 9781138032996 ; , s. 623-627
-
Konferensbidrag (refereegranskat)abstract
- Internationally, geothermal foundations have started to become more common, and their thermal efficiency is being improved. In Sweden, however, energy piles have not been widely used. This is mainly due to the remaining uncertainties in the effect of the thermal cycles on the soft soil response. Under repeated generation and dissipation of excess pore pressures, the microstructure and consequently mechanical properties of soft soils, especially of sensitive (quick) clays that are common in Sweden are significantly alerted. Temperature controlled laboratory tests are required to study the thermal response of soft sensitive clay. This paper introduces a modified oedometer apparatus for the investigation of the temperature dependence of the mechanical properties of clay, with special focus on the creep rate of sensitive clay. © 2016 Taylor & Francis Group, London.
|
|
| 5. |
- Li, Yanling, 1990, et al.
(författare)
-
Thermomechanical Creep in Sensitive Clays
- 2018
-
Ingår i: Journal of Geotechnical and Geoenvironmental Engineering - ASCE. - 1090-0241 .- 1943-5606. ; 144:11
-
Tidskriftsartikel (refereegranskat)abstract
- A systematic series of temperature-controlled oedometer tests on intact and remolded samples of sensitive clay from two depths has been performed. The focus is on studying the temperature effects on the emerging creep rate for a relatively small temperature range, that is, 5 degrees C-25 degrees C, during incremental heating and decremental cooling tests with steps of 5 degrees C. An efficient testing scheme has been developed that exploits the simultaneous testing of several samples. Furthermore, the testing scheme is designed such that no excess pore pressures are generated in the samples during temperature change. The creep rate for intact samples proved to be very sensitive to a temperature change, with the largest effects found for stress levels above the apparent preconsolidation pressure. Heating increments showed larger increases in creep rate than cooling decrements. Both, however, led to a significant change of creep rate in the intact clay samples. In contrast, the reference tests on remolded samples of the same clay that were reconstituted to the in-situ stress state did not show much sensitivity to temperature change. The latter leads to the conclusion that the significant thermal creep triggered in sensitive clays is primarily an effect of the apparent bonding of the natural clay.
|
|
| 6. |
- Middeldorp, Christel M., et al.
(författare)
-
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
-
Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
|
|
| 7. |
- Scheinin, Annalotta, et al.
(författare)
-
Differentiating Drug-related and State-related Effects of Dexmedetomidine and Propofol on the Electroencephalogram
- 2018
-
Ingår i: Anesthesiology. - : Lippincott Williams & Wilkins. - 0003-3022 .- 1528-1175. ; 129:1, s. 22-36
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDDifferentiating drug-related changes and state-related changes on the electroencephalogram during anesthetic-induced unconsciousness has remained a challenge. To distinguish these, we designed a rigorous experimental protocol with two drugs known to have distinct molecular mechanisms of action. We hypothesized that drug- and state-related changes can be separated.METHODS: Forty-seven healthy participants were randomized to receive dexmedetomidine (n = 23) or propofol (n = 24) as target-controlled infusions until loss of responsiveness. Then, an attempt was made to arouse the participant to regain responsiveness while keeping the drug infusion constant. Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness. We conducted statistical comparisons between the drugs and different states of consciousness for spectral bandwidths, and observed how drug-induced electroencephalogram patterns reversed upon awakening. Cross-frequency coupling was also analyzed between slow-wave phase and alpha power.RESULTS: Eighteen (78%) and 10 (42%) subjects were arousable during the constant drug infusion in the dexmedetomidine and propofol groups, respectively (P = 0.011 between the drugs). Corresponding with deepening anesthetic level, slow-wave power increased, and a state-dependent alpha anteriorization was detected with both drugs, especially with propofol. Negative phase-amplitude coupling before and during loss of responsiveness frontally and positive coupling during the highest drug concentration posteriorly were observed in the propofol but not in the dexmedetomidine group.CONCLUSIONS: Electroencephalogram effects of dexmedetomidine and propofol are strongly drug- and state-dependent. Changes in slow-wave and alpha activity seemed to best detect different states of consciousness.
|
|
| 8. |
- Xie, L., et al.
(författare)
-
Structural Hierarchy and Polymorphic Transformation in Shear-Induced Shish-Kebab of Stereocomplex Poly(Lactic Acid)
- 2016
-
Ingår i: Macromolecular rapid communications. - : Wiley-VCH Verlagsgesellschaft. - 1022-1336 .- 1521-3927. ; 37:9, s. 745-751
-
Tidskriftsartikel (refereegranskat)abstract
- The realization of hierarchical shish-kebab structures for stereocomplex poly(lactic acid) (PLA) is achieved by the application of a shear flow (100 s-1 for 1 s) mimicking what can be expected during polymer processing. Compared to the normal shearing scenarios, this transient and strong shear flow enables the creation of dense shish precursors in time- and energy-saving manner. The distribution of crystal form associated with the hierarchical structure is revealed by 2D Fourier transform infrared spectroscopy imaging, creating a unique visualization for both spatial resolution and polymorphism identification. Interestingly, in the shear stereocomplex chains are preferentially extended and crystallized as stable central cores with weak temperature dependence, whereas the development of lateral kebabs is defined by the distinct relation to the crystallization temperature. Below the melting point of homocrystals, both homo and stereocomplex crystallization are engaged in lamellar packing. Above that, exclusive stereocomplex crystals are organized into ordered lamellae. Combining the direct observations at multiscale, the ordered alignment of stereocomplex chains is recognized as the molecular origin of fibrillar extended chain bundles that constitute the central row-nuclei. The proposed hypothesis affords elucidation of shish-kebab formation and unique polymorphism in sheared stereocomplex PLA, which generates opportunities for engendering hierarchically structured PLA with improved performance. A transient and strong shear mimicking the typical melt processing scenario is used to create compact shish-kebab superstructures for stereocomplex poly(lactic acid). The highly oriented fibrillar extended chains are found to constitute the central shish, while 2D Fourier transform infrared spectroscopy imaging offered a direct visualization for determination of polymorphic transition that is associated with spatial hierarchy.
|
|
| 9. |
- Xu, Huan, et al.
(författare)
-
Coffee Grounds to Multifunctional Quantum Dots : Extreme Nanoenhancers of Polymer Biocomposites
- 2017
-
Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:33, s. 27972-27983
-
Tidskriftsartikel (refereegranskat)abstract
- Central to the design and execution of nanocomposite strategies is the invention of polymer-affinitive and multifunctional nanoreinforcements amenable to economically viable processing. Here, a microwave-assisted approach enabled gram-scale fabrication of polymer-affinitive luminescent quantum dots (QDs) from spent coffee grounds. The ultrasmall dimensions (approaching 20 nm), coupled with richness of diverse oxygen functional groups, conferred the zero-dimensional QDs with proper exfoliation and uniform dispersion in poly(L-lactic acid) (PLLA) matrix The unique optical properties of QDs were inherited by PLLA nano composites, giving intensive luminescence and high visible transparency, as well as nearly 100% UV-blocking ratio in the full-UV region at only 0.5 wt % QDs. The strong anchoring of PLLA chains at the nanoscale surfaces of QDs facilitated PLLA crystallization, which was accompanied by substantial improvements in thermomechanical and tensile properties. With 1 wt % QDs, for example, the storage modulus at 100 degrees C and tensile strength increased over 2500 and 69% compared to those of pure PLLA (4 and 57.3 MPa), respectively. The QD-enabled energy-dissipating and flexibility-imparting mechanisms upon tensile deformation, including the generation of numerous shear bands, crazing, and nanofibrillation, gave an unusual combination of elasticity and extensibility for PLLA nanocomposites. This paves the way to biowaste-derived nanodots with high affinity to polymer for elegant implementation of distinct light management and extreme nanoreinforcements in an ecofriendly manner.
|
|
| 10. |
- Xu, Huan, et al.
(författare)
-
Heat-Resistant and Microwaveable Poly(Iactic acid) by Quantum-Dot Promoted Stereocomplexation
- 2017
-
Ingår i: ACS Sustainable Chemistry and Engineering. - : American Chemical Society (ACS). - 2168-0485. ; 5:12, s. 11607-11617
-
Tidskriftsartikel (refereegranskat)abstract
- Nanofiller-tailored stereocomplexation signifies a promising and feasible pathway to develop heat-resistant poly (lactic acid) (PLA) materials. However, this pathway is thwarted by the potential adverse environmental issues of traditional nanofillers and the challenges in facilitating the nanofiller dispersion and selective formation of stereocomplex crystals (SCs). Here we unravel a microwave-assisted approach to exploit biobased quantum dots (QDs) featuring excellent capability to preferably nucleate PLA SCs. The combination of ultrasmall dimension and high oxygenation degree of QDs conferred intimate interactions with stereocomplexed PLA chains, readying complete exfoliation and uniform dispersion of QDs to promote stereocomplexation. The well-dispersed QDs provided perfect UV shielding for PLA composites, while sustaining high transmission to visible light comparable to pure PLA. Strong interfacial interactions and high concentration of SCs were created around the nanoscale surfaces of QDs, accounting for the greatly increased resistance to oxygen permeation, thermal deformation, and microwave heating. This was accompanied by substantial rise in tensile modulus and elongation at break (up to 74 and 51%) compared to that of pure PLA, affording the demonstration of unusual reinforcing and toughening mechanisms imparted by the PLA-affinitive QDs. The robust structural integrity under harsh usage environments, coupled with high gas barrier, prominent light management and evasion of flexibility and extensibility sacrifices, may prompt low-cost and ecofriendly PLA nanocomposites suitable for diverse applications including microwaveable food packaging.
|
|
