Knowledge-based gene expression classification via matrix factorization

Motivation: Modern machine learning methods based on matrix decomposition techniques, like independent component analysis (ICA) or non-negative matrix factorization (NMF), provide new and efficient analysis tools which are currently explored to analyze gene expression profiles. These exploratory feature extraction techniques yield expression modes (ICA) or metagenes (NMF). These extracted features are considered indicative of underlying regulatory processes. They can as well be applied to the classification of gene expression datasets by grouping samples into different categories for diagnostic purposes or group genes into functional categories for further investigation of related metabolic pathways and regulatory networks. Results: In this study we focus on unsupervised matrix factorization techniques and apply ICA and sparse NMF to microarray datasets. The latter monitor the gene expression levels of human peripheral blood cells during differentiation from monocytes to macrophages. We show that these tools are able to identify relevant signatures in the deduced component matrices and extract informative sets of marker genes from these gene expression profiles. The methods rely on the joint discriminative power of a set of marker genes rather than on single marker genes. With these sets of marker genes, corroborated by leave-one-out or random forest cross-validation, the datasets could easily be classified into related diagnostic categories. The latter correspond to either monocytes versus macrophages or healthy vs Niemann Pick C disease patients.Siemens AG, MunichDFG (Graduate College 638)DAAD (PPP Luso - Alem˜a and PPP Hispano - Alemanas

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

First identification of large electric monopole strength in well-deformed rare earth nuclei

Excited states in the well-deformed rare earth isotopes $^{154}$Sm and $^{166}$Er were populated via ``safe'' Coulomb excitation at the Munich MLL Tandem accelerator. Conversion electrons were registered in a cooled Si(Li) detector in conjunction with a magnetic transport and filter system, the Mini-Orange spectrometer. For the first excited $0^+$ state in $^{154}$Sm at 1099 keV a large value of the monopole strength for the transition to the ground state of $\rho^2(\text{E0}; 0^+_2 \to 0^+_\text{g}) = 96(42)\cdot 10^{-3}$ could be extracted. This confirms the interpretation of the lowest excited $0^+$ state in $^{154}$Sm as the collective $\beta$-vibrational excitation of the ground state. In $^{166}$Er the measured large electric monopole strength of $\rho^2(\text{E0}; 0^+_4 \to 0^+_1) = 127(60)\cdot 10^{-3}$ clearly identifies the $0_4^+$ state at 1934 keV to be the $\beta$-vibrational excitation of the ground state.Comment: submitted to Physics Letters

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Low-energy Coulomb excitation of 62^{62}Fe and 62^{62}Mn following in-beam decay of 62^{62}Mn

Sub-barrier Coulomb-excitation was performed on a mixed beam of $^{62}$Mn and $^{62}$Fe, following in-trap $\beta^{-}$ decay of $^{62}$Mn at REX-ISOLDE, CERN. The trapping and charge breeding times were varied in order to alter the composition of the beam, which was measured by means of an ionisation chamber at the zero-angle position of the Miniball array. A new transition was observed at 418~keV, which has been tentatively associated to a $(2^{+},3^{+})\rightarrow1^{+}_{g.s.}$ transition. This fixes the relative positions of the $\beta$-decaying $4^{+}$ and $1^{+}$ states in $^{62}$Mn for the first time. Population of the $2^{+}_{1}$ state was observed in $^{62}$Fe and the cross-section determined by normalisation to the $^{109}$Ag target excitation, confirming the $B(E2)$ value measured in recoil-distance lifetime experiments.Comment: 9 pages, 10 figure

"Safe" Coulomb Excitation of 30Mg

We report on the first radioactive beam experiment performed at the recently commissioned REX-ISOLDE facility at CERN in conjunction with the highly efficient gamma spectrometer MINIBALL. Using 30Mg ions accelerated to an energy of 2.25 MeV/u together with a thin nat-Ni target, Coulomb excitation of the first excited 2+ states of the projectile and target nuclei well below the Coulomb barrier was observed. From the measured relative de-excitation gamma ray yields the B(E2; 0+ -> 2+) value of 30Mg was determined to be 241(31) e2fm4. Our result is lower than values obtained at projectile fragmentation facilities using the intermediate-energy Coulomb excitation method, and confirms the theoretical conjecture that the neutron-rich magnesium isotope 30Mg lies still outside the ``island of inversion''

A magnetically-driven piston pump for ultra-clean applications

A magnetically driven piston pump for xenon gas recirculation is presented. The pump is designed to satisfy extreme purity and containment requirements, as is appropriate for the recirculation of isotopically enriched xenon through the purification system and large liquid xenon TPC of EXO-200. The pump, using sprung polymer gaskets, is capable of pumping more than 16 standard liters per minute (SLPM) of xenon gas with 750 torr differential pressure.Comment: 6 pages, 5 figure

First Results on In-Beam gamma Spectroscopy of Neutron-Rich Na and Mg Isotopes at REX-ISOLDE

After the successful commissioning of the radioactive beam experiment at ISOLDE (REX-ISOLDE) - an accelerator for exotic nuclei produced by ISOLDE - first physics experiments using these beams were performed. Initial experiments focused on the region of deformation in the vicinity of the neutron-rich Na and Mg isotopes. Preliminary results show the high potential and physics opportunities offered by the exotic isotope accelerator REX in conjunction with the modern Germanium gamma spectrometer MINIBALL.Comment: 7 pages, RNB6 conference contributio

Study of 2b-decay of Mo-100 and Se-82 using the NEMO3 detector

After analysis of 5797 h of data from the detector NEMO3, new limits on neutrinoless double beta decay of Mo-100 (T_{1/2} > 3.1 10^{23} y, 90% CL) and Se-82 (T_{1/2} > 1.4 10^{23} y, 90% CL) have been obtained. The corresponding limits on the effective majorana neutrino mass are: m < (0.8-1.2) eV and m < (1.5-3.1) eV, respectively. Also the limits on double-beta decay with Majoron emission are: T_{1/2} > 1.4 10^{22} y (90% CL) for Mo-100 and T_{1/2}> 1.2 10^{22} y (90%CL) for Se-82. Corresponding bounds on the Majoron-neutrino coupling constant are g < (0.5-0.9) 10^{-4} and < (0.7-1.6) 10^{-4}. Two-neutrino 2b-decay half-lives have been measured with a high accuracy, T_{1/2} Mo-100 = [7.68 +- 0.02(stat) +- 0.54(syst) ] 10^{18} y and T_{1/2} Se-82 = [10.3 +- 0.3(stat) +- 0.7(syst) ] 10^{19} y.Comment: 5 pages, 4 figure