Development of a smartphone virtual reality game to support the radiation therapy of children and adolescents in proton centers.

Introduction: For most patients, cancer therapy with radiation is a new experience coming with many unknown challenges. This can be stressful, particularly for children and adolescents. With the aim of reducing this stress and anxiety, a virtual-reality (VR) game, which can be used by patients prior to treatment, was developed and evaluated in a proton therapy center.

Paediatric proton therapy.

Proton beam therapy is a highly conformal form of radiation therapy, which currently represents an important therapeutic component in multidisciplinary management in paediatric oncology. The precise adjustability of protons results in a reduction of radiation-related long-term side-effects and secondary malignancy induction, which is of particular importance for the quality of life. Proton irradiation has been shown to offer significant advantages over conventional photon-based radiotherapy, although the biological effectiveness of both irradiation modalities is comparable.

The hpCADD NDDO Hamiltonian: Parametrization.

A neglect of diatomic differential overlap (NDDO) Hamiltonian has been parametrized as an electronic component of a polarizable force field. Coulomb and exchange potentials derived directly from the NDDO Hamiltonian in principle can be used with classical potentials, thus forming the basis for a new generation of efficiently applicable multipolar polarizable force fields. The new hpCADD Hamiltonian uses force-field-like atom types and reproduces the electrostatic properties (dipole moment, molecular electrostatic potential) and Koopmans' theorem ionization potentials closely, as demonstrated for a large training set and an independent test set of small molecules.

Interaction with mesenchymal stem cells provokes natural killer cells for enhanced IL-12/IL-18-induced interferon-gamma secretion.

Tissue injury induces an inflammatory response accompanied by the recruitment of immune cells and of mesenchymal stem cells (MSC) that contribute to tissue regeneration. After stimulation with interleukin- (IL-) 12 and IL-18 natural killer (NK) cells secrete the proinflammatory cytokine interferon- (IFN-) γ. IFN- γ plays a crucial role in the defense against infections and modulates tissue regeneration.

Improved conditional expression systems resulting in physiological level of HNF4alpha expression confirm HNF4alpha induced apoptosis in the pancreatic beta-cell line INS-1.

Background: To analyze gene function in mammalian cells tetracycline inducible expression of a gene-of-interest at a specific genomic location (Flp-In T-REx) is most attractive. However, leakiness of basal transgene expression and artificially high expression level upon tetracycline addition may be disadvantageous.

Findings: To solve these problems, we developed two different approaches to improve our pancreatic beta-cell line INS-1 Flp-In T-REx expressing the tissue restricted transcription factor HNF4alpha under control of tetracycline.

Tissue-specific transcription factor HNF4alpha inhibits cell proliferation and induces apoptosis in the pancreatic INS-1 beta-cell line.

Hepatocyte nuclear factor 4alpha (HNF4alpha) is a tissue-specific transcription factor expressed in many cell types, including pancreatic beta-cells. Mutations in the HNF4alpha gene in humans give rise to maturity-onset diabetes of the young (MODY1) characterized by defective insulin secretion by beta-cells. To elucidate the mechanism underlying this disease, we introduced the splice form HNF4alpha2 or HNF4alpha8 into the rat beta-cell line INS-1.

Conditional expression of hepatocyte nuclear factor-1beta, the maturity-onset diabetes of the young-5 gene product, influences the viability and functional competence of pancreatic beta-cells.

Mutations in the gene encoding hepatocyte nuclear factor (HNF)1beta result in maturity-onset diabetes of the young-(MODY)5, by impairing insulin secretory responses and, possibly, by reducing beta-cell mass. The functional role of HNF1beta in normal beta-cells is poorly understood; therefore, in the present study, wild-type (WT) HNF1beta, or one of two naturally occurring MODY5 mutations (an activating mutation, P328L329del, or a dominant-negative form, A263insGG) were conditionally expressed in the pancreatic beta-cell line, insulin-1 (INS-1), and the functional consequences examined. Surprisingly, overexpression of the dominant-negative mutant did not modify any of the functional properties of the cells studied (including insulin secretion, cell growth and viability).

Pattern of genes influenced by conditional expression of the transcription factors HNF6, HNF4alpha and HNF1beta in a pancreatic beta-cell line.

Using the rat insulinoma cell line INS-1 we generated beta-cell clones that are most efficient for gene transfer, as they contain an FRT site for Flp recombinase-mediated, site-directed integration of a single copy transgene. Therefore, the gene-of-interest can be introduced by DNA transfection without the need to select individual cell clones. Additionally, the clones contain the tetracycline repressor allowing tetracycline induction of the transgene.

Distinct molecular and morphogenetic properties of mutations in the human HNF1beta gene that lead to defective kidney development.

The homeobox transcription factor hepatocyte nuclear factor 1beta (HNF1beta) is a tissue-specific regulator that plays an essential role in early vertebrate development. In humans, heterozygous mutations in the HNF1beta gene are associated with young-onset diabetes as well as a variety of disorders of renal development with cysts as the most consistent feature. This report compares and classifies nine different HNF1beta mutations that lead in humans to distinct renal diseases, including solitary functioning kidney, renal dysplasia, glomerulocystic kidney disease, and oligomeganephronia.

Behavioural and microdialysis study after neurotoxic lesion of the dorsal raphe nucleus in rats.

The study investigated the effects of a 5,7-dihydroxytryptamine (5,7-DHT) lesion of the dorsal raphe nucleus (DRN) on anxiety-related behaviour and neurochemical correlates in rats. Behaviour was assessed in the elevated plus maze test (X-maze). Lesion of the DRN reduced markedly 5-HT levels in projection areas by at least 60%.

Evidence for haploinsufficiency of the human HNF1alpha gene revealed by functional characterization of MODY3-associated mutations.

Hepatocyte nuclear factor (HNF)1alpha is a homeo-domain-containing transcription factor participating in the regulation of gene expression in liver, kidney, gut and pancreas of vertebrates. In humans mutations in the HNF1 gene are responsible for one form of maturity onset diabetes of the young (MODY3). To define the molecular mechanism underlying MODY3 we investigated the functional properties of seven MODY3-associated mutations representing the spectrum of different kinds of mutations affecting all functional domains of the protein.