Overexpression of activin A in the skin of transgenic mice reveals new activities of activin in epidermal morphogenesis, dermal fibrosis and wound repair.

in EMBO Journal (1999), 18(19), 5205-15

Recently we demonstrated a strong induction of activin expression after skin injury, suggesting a function of this transforming growth factor-beta family member in wound repair. To test this possibility ... [more ▼]

Recently we demonstrated a strong induction of activin expression after skin injury, suggesting a function of this transforming growth factor-beta family member in wound repair. To test this possibility, we generated transgenic mice that overexpress the activin betaA chain in the epidermis under the control of a keratin 14 promoter. The transgenic mice were significantly smaller than control littermates, and they had smaller ears and shorter tails. In their skin, the fatty tissue was replaced by connective tissue and a severe thickening of the epidermis was found. The spinous cell layer was significantly increased, and the epidermal architecture was highly disorganized. These histological abnormalities seem to result from increased proliferation of the basal keratinocytes and abnormalities in the program of keratinocyte differentiation. After skin injury, a significant enhancement of granulation tissue formation was detected in the activin-overexpressing mice, possibly as a result of premature induction of fibronectin and tenascin-C expression. These data reveal novel activities of activin in the regulation of keratinocyte proliferation and differentiation as well as in dermal fibrosis and cutaneous wound repair. [less ▲]

Overexpression of synphilin-1 promotes clearance of soluble and misfolded alpha-synuclein without restoring the motor phenotype in aged A30P transgenic mice.

in Human molecular genetics (2014), 23(3), 767-81

Lewy bodies and neurites are the pathological hallmark of Parkinson's disease. These structures are composed of fibrillized and ubiquitinated alpha-synuclein suggesting that impaired protein clearance is ... [more ▼]

Lewy bodies and neurites are the pathological hallmark of Parkinson's disease. These structures are composed of fibrillized and ubiquitinated alpha-synuclein suggesting that impaired protein clearance is an important event in aggregate formation. The A30P mutation is known for its fast oligomerization, but slow fibrillization rate. Despite its toxicity to neurons, mechanisms involved in either clearance or conversion of A30P alpha-synuclein from its soluble state into insoluble fibrils and their effects in vivo are poorly understood. Synphilin-1 is present in Lewy bodies, interacting with alpha-synuclein in vivo and in vitro and promotes its sequestration into aggresomes, which are thought to act as cytoprotective agents facilitating protein degradation. We therefore crossed animals overexpressing A30P alpha-synuclein with synphilin-1 transgenic mice to analyze its impact on aggregation, protein clearance and phenotype progression. We observed that co-expression of synphilin-1 mildly delayed the motor phenotype caused by A30P alpha-synuclein. Additionally, the presence of N- and C-terminal truncated alpha-synuclein species and fibrils were strongly reduced in double-transgenic mice when compared with single-transgenic A30P mice. Insolubility of mutant A30P and formation of aggresomes was still detectable in aged double-transgenic mice, paralleled by an increase of ubiquitinated proteins and high autophagic activity. Hence, this study supports the notion that co-expression of synphilin-1 promotes formation of autophagic-susceptible aggresomes and consecutively the degradation of human A30P alpha-synuclein. Notably, although synphilin-1 overexpression significantly reduced formation of fibrils and astrogliosis in aged animals, a similar phenotype is present in single- and double-transgenic mice suggesting additional neurotoxic processes in disease progression. [less ▲]

Overexpression of the sarcolemmal calcium pump in the myocardium of transgenic rats.

in Circulation Research (1998), 83(9), 877-88

The plasma membrane calmodulin-dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca2+ homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because ... [more ▼]

The plasma membrane calmodulin-dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca2+ homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because of the presence of the Na+/Ca2+ exchanger. We approached the question of the physiological function of the calcium pump using a transgenic "gain of function" model. Transgenic rat lines carrying the human PMCA 4 cDNA under control of the ventricle-specific myosin light chain-2 promoter were established, and expression in the myocardium was ascertained at the mRNA, protein, and functional levels. In vivo hemodynamic measurements in adult homozygous animals showed no differences in baseline and increased cardiac performance recruited by volume overload compared with controls. No differences between transgenic and control cardiomyocytes were found in patch clamp voltage dependence, activation/inactivation behavior of the L-type Ca2+ current, or fast [Ca2+]i transients (assessed by the Fura-2 method). To test whether the PMCA might be involved in processes other than beat-to-beat regulation of contraction/relaxation, we compared growth processes of neonatal transgenic and control cardiomyocytes. A 1.6- and 2.3-fold higher synthesis rate of total protein was seen in cells from transgenic animals compared with controls on incubation with 2% FCS for 24 hours and 36 hours, respectively. An effect of similar magnitude was observed using 20 micromol/L phenylephrine. A 1.4-fold- and 2.0-fold-higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively. Because pivotal parts of the alpha- and beta-adrenergic signal transduction pathways recently have been localized to caveolae, we tested the hypothesis that the PMCA might alter the amplitude of alpha- and beta-adrenergic growth signals by virtue of its localization in caveolae. Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes. These results indicate that the sarcolemmal Ca2+-pump has little relevance for beat-to-beat regulation of contraction/relaxation in adult animals but likely plays a role in regulating myocardial growth, possibly through modulation of caveolar signal transduction. [less ▲]

Overgrowth of wrinkled InGaAs membranes using molecular beam epitaxy

in Journal of Crystal Growth (2015), 425

Partly released InGaAs layers forming a wrinkled network are used as templates for InAs growth. A systematic growth study was carried out, where InAs amounts from 0 ML to 3 ML were deposited on the ... [more ▼]

Partly released InGaAs layers forming a wrinkled network are used as templates for InAs growth. A systematic growth study was carried out, where InAs amounts from 0 ML to 3 ML were deposited on the patterned samples. The material migration during growth is evaluated by distinct microscopy techniques. We find a systematic accumulation of the deposited material on the released, wrinkled areas of the sample, whereas no material accumulation or formation of three-dimensional nanostructures is observed on the unreleased areas of the sample. [less ▲]

Overloaded Satellite Receiver using SIC with Hybrid Beamforming and ML detection

in 14th Workshop on Signal Processing Advances in Wireless Communications (SPAWC) (2013, June)

In this paper, a new receiver structure that is intended to detect the signals from multiple adjacent satellites in the presence of other interfering satellites is proposed. We tackle the worst case ... [more ▼]

In this paper, a new receiver structure that is intended to detect the signals from multiple adjacent satellites in the presence of other interfering satellites is proposed. We tackle the worst case interference conditions, i.e., it is assumed that uncoded signals that fully overlap in frequency arrive at a multiple-element small-size parabolic antenna in a spatially correlated noise environment. The proposed successive interference cancellation (SIC) receiver, denoted by SIC Hy/ML, employs hybrid beamforming and disjoint maximum likelihood (ML) detection. Depending on the individual signals spatial position, the proposed SIC Hy/ML scheme takes advantage of two types of beamformers: a maximum ratio combining (MRC) beamformer and a compromised array response (CAR) beamformer. The performance of the proposed receiver is compared to an SIC receiver that uses only MRC beamforming scheme with ML detection for all signals, a joint ML detector, and a minimum mean square error detector. It is found that SIC Hy/ML outperforms the other schemes by a large margin. [less ▲]

Overloads Management in Active Radial Distribution Systems: an Optimization Approach Including Network Switching

in 2013 IEEE PES PowerTech (2013, June)

This paper focuses on the real-time overloads management in active radial distribution systems that host a significant amount of distributed generators (DGs). In order to possibly reduce the amount of ... [more ▼]

This paper focuses on the real-time overloads management in active radial distribution systems that host a significant amount of distributed generators (DGs). In order to possibly reduce the amount of generation curtailed to remove congestion, and hence harvest as much renewable energy as possible, we propose a centralized optimization approach that includes the option to use remotely controlled grid switches and breakers so as to transfer distributed generation between feeders. To mitigate the computational burden posed by modeling the switching actions as binary variables we build upon a very convenient existing optimization framework that, for a radial distribution grid, transforms precisely the original mixed integer nonlinear programming (MINLP) problem into a much simpler mixed integer quadratically constrained (MIQC) one. Although the approach focuses on overload removal in course of optimization it also pays attention not worsening other operational constraints such as voltage limits. We prove the interest and feasibility of our approach using a 33-bus benchmark distribution system as well as a 61-bus real-life distribution system model. [less ▲]

Overnight metabolic profiles in very young insulin-dependent diabetic children

in European Journal of Pediatrics (1986), 145(1-2), 73-76

The magnitude of the disturbance of metabolic control in diabetes mellitus in very young children has been recognised, but seldom studied. Limitations to studies are set by the difficulty of obtaining ... [more ▼]

The magnitude of the disturbance of metabolic control in diabetes mellitus in very young children has been recognised, but seldom studied. Limitations to studies are set by the difficulty of obtaining control data and until recently the lack of alternative therapies. Recently "mini" pumps for continuous subcutaneous insulin delivery have become available and may offer an alternative therapeutic possibility. The present investigation has been undertaken to collect overnight metabolic data of very young diabetic children (<6 years) controlled by standard injection therapy. During one admission to hospital frequent blood samples were collected for free insulin, glucose, alanine, lactate, glycerol and 3-hydroxybutyrate determinations. In all children (n=9) the profiles showed a steep rise in glucose from 04.30h (6.2±1.3 mmol/l) to 09.30h (17.8±2.4 mmol/l) (the so-called "dawn-phenomenon"). The nature of the changes in the intermediary metabolites suggested that rise in blood glucose was caused by insufficient insulin. We have attempted to explore the time relationship between the overnight drop in free insulin levels and the rises in blood glucose by a distribution-free statistical analysis, correlating successive changes in time between the two profiles. The analysis suggested a delay of 2-6 h between free insulin levels and their effects. In conclusion: a clear "dawn phenomenon" is seen in very young diabetic children, and contributes to their poor glycaemic control. More stable and higher insulin concentrations in the early morning, obtained perhaps by continuous subcutaneous insulin infusion, might ameliorate the overall glycaemic control in the very young diabetic child. © 1986 Springer-Verlag. [less ▲]

Overprosecution and Negotiated Justice in Europe

in Van Kempen, Piet Hein (Ed.) Overuse in the Criminal Justice System: On Criminalization, Prosecution and Imprisonment (2019)

Oversized Populations and Cooperative Selection: Dealing with Massive Resources in Parallel Infrastructures

in Nicosia, G.; Pardalos, P. (Eds.) Learning and Intelligent Optimization (2013)

This paper proposes a new selection scheme for Evolutionary Algorithms (EAs) based on altruistic cooperation between individuals. Cooperation takes place every time an individual undergoes selection: the ... [more ▼]

This paper proposes a new selection scheme for Evolutionary Algorithms (EAs) based on altruistic cooperation between individuals. Cooperation takes place every time an individual undergoes selection: the individual decreases its own fitness in order to improve the mating chances of worse individuals. On the one hand, the selection scheme guarantees that the genetic material of fitter individuals passes to subsequent generations as to decrease their fitnesses individuals have to be firstly selected. On the other hand, the scheme restricts the number of times an individual can be selected not to take over the entire population. We conduct an empirical study for a parallel EA version where cooperative selection scheme is shown to outperform binary tournament: both selection schemes yield the same qualities of solutions but cooperative selection always improves the times to solutions. [less ▲]

Overview and Challenges of the UL HPC Facility at the Belval and EuroHPC Horizon

Presentation (2017, June)