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Cerebral creatine kinase deficiency influences metabolite levels and morphology in the mouse brain : a quantitative in vivo 1H and 31P magnetic resonance study

Creatine kinase (CK)-catalysed ATP-phosphocreatine (PCr) exchange is considered to play a key role in energy homeostasis of the brain. This study assessed the metabolic and anatomical consequences of partial or complete depletion of this system in transgenic mice without cytosolic B-CK (B-CK-/-), mitochondrial ubiquitous CK (UbCKmit-/-), or both isoenzymes (CK -/-), using non-invasive quantitative

Scarred Uterus: Subsequent Pregnancy and Delivery

The aim of the work presented in this thesis was to address the problems associated with the management of pregnancy and delivery after Caesarean delivery (CD), with emphasis on ultrasound diagnostics. The prognostic value and utility of serial ultrasound examinations of Caesarean hysterotomy scars in the non-pregnant state and during pregnancy subsequent to CD were studied. This thesis includes 5

Self-gated fetal cardiac MRI with tiny golden angle iGRASP : A feasibility study

PURPOSE: To develop and assess a technique for self-gated fetal cardiac cine magnetic resonance imaging (MRI) using tiny golden angle radial sampling combined with iGRASP (iterative Golden-angle RAdial Sparse Parallel) for accelerated acquisition based on parallel imaging and compressed sensing.MATERIALS AND METHODS: Fetal cardiac data were acquired from five volunteers in gestational week 29-37 a

Effects of caffeine abstinence on adenosine induced coronary flow reserve quantified on phase contrast velocity encoded MRI of the coronary sinus

Introduction: Adenosine is a common pharmacological vasodilator agent used in first pass perfusion MRI as well as nuclear cardiology and echocardiography. Coronary flow reserve (CFR) by adenosine is inhibited by caffeine and therefore caffeine abstinence is routinely proscribed in patients. However, the guidelines differ regarding how long abstinence is needed from 12 to 24 hours. Purpose: This st

Experimental evidence for the 8B ground state configuration

The 7Be fragments produced in one-proton removal from relativistic 8B nuclei of 936 MeV/nucleon in a carbon target have been detected in coincidence with γ rays emitted by these fragments at the reaction target. It is found that 13 ± 3% of the 7Be fragments are released in the 429 keV excited state, 7Be*, which gives direct experimental information on the ground state configuration of 8B. The long

One-nucleon removal cross-sections for 17,19C and 8,10B

One-neutron removal cross-sections (σ-1n) of 17,19C in various targets at about 900 MeV/nucleon, and one-proton removal cross-sections (σ-1p) of 8,10B at about 1400 MeV/nucleon were measured using the fragment separator FRS at GSI. A significant increase of σ-1n for 19C compared to its neighbors was observed. The same behavior was found for σ-1p for the neutron-deficient nucleus 8B compared to the

Two-neutron interferometry as a probe of the nuclear halo

The technique of intensity interferometry is proposed as a probe of the spatial configuration of two-Neutron haloes. After exploring the sensitivity of interferometry to the n-N configuration, it is demonstrated that the application of the standard method for constructing the correlation function is not valid for halo neutrons. A new iterative method is presented and applied to measurements of the

New results on the halo structure of 8B

The longitudinal momentum distribution of Be fragments after fragmentation of B and the one-proton removal cross section (σ-1p) in a carbon target were measured at 1440 MeV/u with the fragment separator FRS used as an energy-loss spectrometer. The results show a narrow momentum distribution with a FWHM value of 91 ± 5 MeV/c and a large cross-section, σ-1p = 98 ± 6 mb. Both these results support th

One-nucleon removal reactions at the FRS

The fragment separator FRS at GSI was used as an energy-loss spectrometer to study the nuclear structure of exotic light nuclei via nucleon-removal reactions. The measurements performed include the longitudinal momentum distributions of fragments after one-nucleon removal, the one-nucleon removal cross-sections and in some cases the coincident detection of gamma rays emitted from the breakup fragm

Longitudinal momentum distributions of 16,18C fragments after one-neutron removal from 17,19C

The fragment separator FRS at GSI was used as an energy-loss spectrometer to measure the longitudinal momentum distributions of 16,18C fragments after one-neutron removal reactions in 17,19C impinging on a carbon target at about 910 MeV/u. The distributions in the projectile frames are characterized by a FWHM of 141 ± 6 MeV/c for 16C and 69 ± 3 MeV/c for 18C. The results are compared with experime

Highly lying α-cluster states in the light nuclei 16O, 20Ne, 22Ne, and 24Mg

The excitation functions for elastic α-particle scattering by 12C, 16O, 18O, and 20Ne at 180° in the c.m.s. are determined in wide energy ranges by using the new method of elastic resonance scattering on a thick target in inverse kinematics. In favorable cases, the method makes it possible to reduce considerably the time required for obtaining excitation curves. General regularities observed in th

Systematic investigation of the drip-line nuclei 11Li and 14Be and their unbound subsystems 10Li and 13Be

Fragmentation reactions in a carbon target with beams of 11Li and 14Be at relativistic energies have been studied in a kinematically complete experiment at the ALADIN-LAND setup at GSI. Excited states in 11Li and 14Be were obtained from the data in the inelastic channel. The measured cross sections with the core nucleus in the final state show that in the 14Be case core polarization plays an impor

Marketing for start-ups

The chapter focuses on marketing activities of start-up firms. While this is traditionally understood as analyzing the customer needs and how to bridge that gap, for example, through segmentation and branding activities, this chapter has focused on bridging the gaps between industrial actors in order to build networks. The rationale behind this focus relates to the fact that science- and technolog

Transgenic Expression of the Mitochondrial Chaperone TNFR-associated Protein 1 (TRAP1) Accelerates Prostate Cancer Development

Protein homeostasis, or proteostasis, is required for mitochondrial function, but its role in cancer is controversial. Here we show that transgenic mice expressing the mitochondrial chaperone TNFR-associated protein 1 (TRAP1) in the prostate develop epithelial hyperplasia and cellular atypia. When examined on a Pten(+/-) background, a common alteration in human prostate cancer, TRAP1 transgenic mi

Deletion of Cyclophilin D Impairs β-Oxidation and Promotes Glucose Metabolism

Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid β-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulati

Adaptive mitochondrial reprogramming and resistance to PI3K therapy

BACKGROUND: Small molecule inhibitors of phosphatidylinositol-3 kinase (PI3K) have been developed as molecular therapy for cancer, but their efficacy in the clinic is modest, hampered by resistance mechanisms.METHODS: We studied the effect of PI3K therapy in patient-derived tumor organotypic cultures (from five patient samples), three glioblastoma (GBM) tumor cell lines, and an intracranial model

Deletion of the mitochondrial chaperone TRAP-1 uncovers global reprogramming of metabolic networks

Reprogramming of metabolic pathways contributes to human disease, especially cancer, but the regulators of this process are unknown. Here, we have generated a mouse knockout for the mitochondrial chaperone TRAP-1, a regulator of bioenergetics in tumors. TRAP-1(-/-) mice are viable and showed reduced incidence of age-associated pathologies, including obesity, inflammatory tissue degeneration, dyspl

DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation and doxorubicin

DNA-dependent protein kinase (DNA-PK) plays a key role in the repair of DNA double-strand breaks (DSBs) that are probably the most deleterious form of DNA damage. Inhibition of DNA-PK has been considered as an attractive approach to decrease resistance to therapeutically induced DNA DSBs. Ionizing radiation (IR) and doxorubicin, which induce DSBs, are used in the treatment of breast cancer. We det

Cyclophilin D extramitochondrial signaling controls cell cycle progression and chemokine-directed cell motility

Mitochondria control bioenergetics and cell fate decisions, but how they influence nuclear gene expression is understood poorly. Here, we show that deletion or reduction in the levels of cyclophilin D (CypD, also called Ppif), a mitochondrial matrix peptidyl prolyl isomerase and apoptosis regulator, results in increased cell proliferation and enhanced cell migration and invasion. These responses a

Chk2 phosphorylation of survivin-DeltaEx3 contributes to a DNA damage-sensing checkpoint in cancer

Survivin is an oncogene that functions in cancer cell cytoprotection and mitosis. Here we report that differential expression in cancer cells of a C-terminal splice variant of survivin, termed survivin-ΔEx3, is tightly associated with aggressive disease and markers of unfavorable prognosis. In contrast to other survivin variants, survivin-ΔEx3 localized exclusively to nuclei in tumor cells and was