Final State Interaction in Exclusive (e,e′NN)(e,e'NN) Reactions

Contributions of nucleon-nucleon (NN) correlations, meson exchange currents and the residual final state interactions (FSI) on exclusive two-nucleon knock-out reactions induced by electron scattering are investigated. All contributions are derived from the same realistic meson exchange model for the NN interaction. Effects of correlations and FSI are determined in a consistent way by solving the NN scattering equation, the Bethe-Goldstone equation, for two nucleons in nuclear matter. One finds that the FSI re-scattering terms are non-negligible even if the two nucleons are emitted back to back.Comment: 8 pages, 5 figure

Electromagnetic proton-neutron knockout off 16O: new achievements in theory

Results for the cross sections of the exclusive 16O(e,e'pn)14N and 16O(gamma,pn)14N knockout reactions are presented and discussed in different kinematics. In comparison with earlier work, a complete treatment of the center-of-mass (CM) effects in the nuclear one-body current is considered in connection with the problem of the lack of orthogonality between initial bound and final scattering states. The effects due to CM and orthogonalization are investigated in combination with different treatments of correlations in the two-nucleon overlap function and for different parametrizations of the two-body currents. The CM effects lead in super-parallel kinematics to a dramatic increase of the 16O(e,e'pn) cross section to the 1_2^+ excited state (3.95 MeV) of 14N. In all the situations considered the results are very sensitive to the treatment of correlations. A crucial role is played by tensor correlations, but also the contribution of long-range correlations is important.Comment: 13 pages, 10 figure

NN final-state interaction in two-nucleon knockout from 16O^{16}O

The influence of the mutual interaction between the two outgoing nucleons (NN-FSI) in electro- and photoinduced two-nucleon knockout from $^{16}O$ has been investigated perturbatively. It turns out that the effect of NN-FSI depends on the kinematics and on the type of reaction considered. The effect is generally larger in pp- than in pn-knockout and in electron induced than in photoinduced reactions. In superparallel kinematics NN-FSI leads in the $(e,e'pp)$ channel to a strong increase of the cross section, that is mainly due to a strong enhancement of the $\Delta$-current contribution. In pn-emission, however, this effect is partially cancelled by a destructive interference with the seagull current. For photoreactions NN-FSI is considerably reduced in superparallel kinematics and can be practically negligible in specific kinematics.Comment: 16 pages, 9 figure

Nucleon-Nucleon Correlations and Two-Nucleon Currents in Exclusive (e,e′NNe,e'NN) Reactions

The contributions of short-range nucleon-nucleon (NN) correlations, various meson exchange current (MEC) terms and the influence of $\Delta$ isobar excitations (isobaric currents, IC) on exclusive two-nucleon knockout reactions induced by electron scattering are investigated. The nuclear structure functions are evaluated for nuclear matter. Realistic NN interactions derived in the framework of One-Boson-Exchange model are employed to evaluate the effects of correlations and MEC in a consistent way. The correlations correlations are determined by solving the Bethe-Goldstone equation. This yields significant contributions to the structure functions W_L and W_T of the (e,e'pn) and (e,e'pp) reactions. These contributions compete with MEC corrections originating from the $\pi$ and $\rho$ exchange terms of the same interaction. Special attention is paid to the so-called 'super parallel' kinematics at momentum transfers which can be measured e.g. at MAMI in Mainz.Comment: 14 pages, 8 figures include

A model for two-proton emission induced by electron scattering

A model to study two-proton emission processes induced by electron scattering is developed. The process is induced by one-body electromagnetic operators acting together with short-range correlations, and by two-body $\Delta$ currents. The model includes all the diagrams containing a single correlation function. A test of the sensitivity of the model to the various theoretical inputs is done. An investigation of the relevance of the $\Delta$ currents is done by changing the final state angular momentum, excitation energy and momentum transfer. The sensitivity of the cross section to the details of the correlation function is studied by using realistic and schematic correlations. Results for $^{12}$C, $^{16}$O and $^{40}$Ca nuclei are presented.Comment: 30 pages, 18 figures, 3 table

Expression of yeast lipid phosphatase Sac1p is regulated by phosphatidylinositol-4-phosphate

<p>Abstract</p> <p>Background</p> <p>Phosphoinositides play a central role in regulating processes at intracellular membranes. In yeast, a large number of phospholipid biosynthetic enzymes use a common mechanism for transcriptional regulation. Yet, how the expression of genes encoding lipid kinases and phosphatases is regulated remains unknown.</p> <p>Results</p> <p>Here we show that the expression of lipid phosphatase Sac1p in the yeast <it>Saccharomyces cerevisiae </it>is regulated in response to changes in phosphatidylinositol-4-phosphate (PI(4)P) concentrations. Unlike genes encoding enzymes involved in phospholipid biosynthesis, expression of the <it>SAC1 </it>gene is independent of inositol levels. We identified a novel 9-bp motif within the 5' untranslated region (5'-UTR) of <it>SAC1 </it>that is responsible for PI(4)P-mediated regulation. Upregulation of <it>SAC1 </it>promoter activity correlates with elevated levels of Sac1 protein levels.</p> <p>Conclusion</p> <p>Regulation of Sac1p expression via the concentration of its major substrate PI(4)P ensures proper maintenance of compartment-specific pools of PI(4)P.</p

Local erythropoietin and endothelial progenitor cells improve regional cardiac function in acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Expanded endothelial progenitor cells (eEPC) improve global left ventricular function in experimental myocardial infarction (MI). Erythropoietin beta (EPO) applied together with eEPC may improve regional myocardial function even further by anti-apoptotic and cardioprotective effects. Aim of this study was to evaluate intramyocardial application of eEPCs and EPO as compared to eEPCs or EPO alone in experimental MI.</p> <p>Methods and Results</p> <p>In vitro experiments revealed that EPO dosed-dependently decreased eEPC and leukocyte apoptosis. Moreover, in the presence of EPO mRNA expression in eEPC of proangiogenic and proinflammatory mediators measured by TaqMan PCR was enhanced. Experimental MI was induced by ligation and reperfusion of the left anterior descending coronary artery of nude rats (n = 8-9). After myocardial transplantation of eEPC and EPO CD68+ leukocyte count and vessel density were enhanced in the border zone of the infarct area. Moreover, apoptosis of transplanted CD31 + TUNEL + eEPC was decreased as compared to transplantation of eEPCs alone. Regional wall motion of the left ventricle was measured using Magnetic Resonance Imaging. After injection of eEPC in the presence of EPO regional wall motion significantly improved as compared to injection of eEPCs or EPO alone.</p> <p>Conclusion</p> <p>Intramyocardial transplantation of eEPC in the presence of EPO during experimental MI improves regional wall motion. This was associated with an increased local inflammation, vasculogenesis and survival of the transplanted cells. Local application of EPO in addition to cell therapy may prove beneficial in myocardial remodeling.</p

Comprehensive CRISPR-Cas9 screens identify genetic determinants of drug responsiveness in multiple myeloma

The introduction of new drugs in the past years has substantially improved outcome in multiple myeloma (MM). However, the majority of patients eventually relapse and become resistant to one or multiple drugs. While the genetic landscape of relapsed/ resistant multiple myeloma has been elucidated, the causal relationship between relapse-specific gene mutations and the sensitivity to a given drug in MM has not systematically been evaluated. To determine the functional impact of gene mutations, we performed combined whole-exome sequencing (WES) of longitudinal patient samples with CRISPR-Cas9 drug resistance screens for lenalidomide, bortezomib, dexamethasone, and melphalan. WES of longitudinal samples from 16 MM patients identified a large number of mutations in each patient that were newly acquired or evolved from a small subclone (median 9, range 1-55), including recurrent mutations in TP53, DNAH5, and WSCD2. Focused CRISPR-Cas9 resistance screens against 170 relapse-specific mutations functionally linked 15 of them to drug resistance. These included cereblon E3 ligase complex members for lenalidomide, structural genes PCDHA5 and ANKMY2 for dexamethasone, RB1 and CDK2NC for bortezomib, and TP53 for melphalan. In contrast, inactivation of genes involved in the DNA damage repair pathway, including ATM, FANCA, RAD54B, and BRCC3, enhanced susceptibility to cytotoxic chemotherapy. Resistance patterns were highly drug specific with low overlap and highly correlated with the treatment-dependent clonal evolution in patients. The functional association of specific genetic alterations with drug sensitivity will help to personalize treatment of MM in the future