Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of ...pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.
Semiconductor quantum dots in silicon are promising qubits because of long spin coherence times and their potential for scalability. However, such qubits with complete electrical control and ...fidelities above the threshold for quantum error correction have not yet been achieved. We show theoretically that the threshold fidelity can be achieved with ac gate operation of the quantum dot hybrid qubit. Formed by three electrons in a double dot, this qubit is electrically controlled, does not require magnetic fields, and runs at gigahertz (GHz) gate speeds. We analyze the decoherence caused by 1/f charge noise in this qubit, find parameters that minimize the charge noise dependence in the qubit frequency, and determine the optimal working points for ac gate operations that drive the detuning and tunnel coupling.
The recent observation of a hadronic resonance d⁎ in the proton–neutron system with isospin I=0 and spin-parity JP=3+ raises the possibility of producing other novel six-quark dibaryon configurations ...allowed by QCD. A dramatic example of an exotic six-quark color-singlet system is the charge Q=+4, isospin I=3, Iz=+3|uuuuuu〉 state which couples strongly to Δ+++Δ++. The width and decay properties of such six-quark resonances could be regarded as manifestations of “hidden-color” six-quark configurations, a first-principle prediction of QCD – SU(3)-color gauge theory for the deuteron distribution amplitude. Other implications and possible future experiments are discussed.
A review is given about the long-standing search for dibaryons, i.e. six-quark objects, from the early days until present, when the first dibaryon resonance has been established, which has the ...potential of constituting a compact six-quark object.
When hydraulic power take off (PTO) is used to convert the mechanical energy of a wave energy converter (WEC) into a more useful form of energy, the PTO force needs to be controlled. Continuous ...controlled variation of the PTO force can be approximated by a set of discrete values. This can be implemented using either variable displacement pumps or several hydraulic cylinders or several high pressure accumulators with different pressure levels. This pseudo-continuous control could lead to a complex PTO with a lot of components. A simpler way for controlling this hydraulic PTO is declutching control, which consists in switching on and off alternatively the wave energy converter's PTO. This can be achieved practically using a simple by-pass valve. In this paper, the control law of the valve is determined by using the optimal command theory. It is shown that, theoretically when considering a wave activated body type of WEC, declutching control can lead to energy absorption performance at least equivalent to that of pseudo-continuous control. The method is then applied to the case of the SEAREV wave energy converter, and it is shown than declutching control can even lead to a higher energy absorption, both in regular and irregular waves.
Upon incorporation of nanoparticles (NPs) into the body, they are exposed to biological fluids, and their interaction with the dissolved biomolecules leads to the formation of the so-called protein ...corona on the surface of the NPs. The composition of the corona plays a crucial role in the biological fate of the NPs. While the effects of various physicochemical parameters on the composition of the corona have been explored in depth, the role of temperature upon its formation has received much less attention. In this work, we have probed the effect of temperature on the protein composition on the surface of a set of NPs with various surface chemistries and electric charges. Our results indicate that the degree of protein coverage and the composition of the adsorbed proteins on the NPs’ surface depend on the temperature at which the protein corona is formed. Also, the uptake of NPs is affected by the temperature. Temperature is, thus, an important parameter that needs to be carefully controlled in quantitative studies of bionano interactions.
Oct4 was reported to be one of the most important pluripotency transcription factors in the biology of stem cells including cancer stem cells, and progressed malignant cells. Here we report the ...investigation of gene expression control of Oct4 by selected human microRNAs and the physiological effect of Oct4 silencing in invasive cancer cells.
High throughput luciferase activity assay revealed the microRNA-299-3p to be the most effective in reducing gene expression of Oct4, which was confirmed by Western blot analysis and Oct4 promoter activity in a target luciferase assay. Furthermore, it could be demonstrated that downregulation of Oct4 by microRNAs-299-3p in breast cancer and fibrosarcoma cells lead to a decreased invasiveness in a microfluidic chip assay. Additionally, microRNA-299-3p causes apoptosis in cancer cells. Comparison with Oct4 specific siRNA transfection confirmed that this effect is primary due to the blockade of Oct4 expression.
The results suggest that microRNA-299-3p is an interesting target for potential clinical use. It may be able to decrease invasive behaviour of carcinoma cells; or even kill these cells by causing apoptosis.
Polysaccharide (PS) based nanoparticles (NP) are of great interest for biomedical applications. A key challenge in this regard is the functionalization of these nanomaterials. The aim of the present ...work was the development of reactive PS-NP that can be coupled with an amino group containing compounds under mild aqueous conditions. A series of cellulose phenyl carbonates (CPC) and xylan phenyl carbonates (XPC) with variable degrees of substitution (DS) was obtained by homogeneous synthesis. The preparation of PS-NP by self-assembling of these hydrophobic derivatives was studied comprehensively. While CPC mostly formed macroscopic aggregates, XPC formed well-defined spherical NP with diameters around 100 to 200 nm that showed a pronounced long-term stability in water against both particle aggregation as well as cleavage of phenyl carbonate moieties. Using an amino group functionalized dye it was demonstrated that the novel XPC-NP are reactive towards amines. A simple coupling procedure was established that enables direct functionalization of the reactive NP in an aqueous dispersion. Finally, it was demonstrated that dye functionalized XPC-NP are non-cytotoxic and can be employed in advanced biomedical applications.
Manganese is an essential transition metal that, among other functions, can act independently of proteins to either defend against or promote oxidative stress and disease. The majority of cellular ...manganese exists as low molecular-weight Mn²⁺ complexes, and the balance between opposing "essential" and "toxic" roles is thought to be governed by the nature of the ligands coordinating Mn²⁺. Until now, it has been impossible to determine manganese speciation within intact, viable cells, but we here report that this speciation can be probed through measurements of ¹H and ³¹P electron-nuclear double resonance (ENDOR) signal intensities for intracellular Mn²⁺. Application of this approach to yeast (Saccharomyces cerevisiae) cells, and two pairs of yeast mutants genetically engineered to enhance or suppress the accumulation of manganese or phosphates, supports an in vivo role for the orthophosphate complex of Mn²⁺ in resistance to oxidative stress, thereby corroborating in vitro studies that demonstrated superoxide dismutase activity for this species.
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