Gamma Efficiency Simulations towards Coincidence Measurements for Fusion Cross Sections

With the experimental station STELLA (STELlar LAboratory) we will measure fusion cross sections of astrophysical relevance making use of the coincident detection of charged particles and gamma rays for background reduction. For the measurement of gamma rays from the de-excitation of fusion products a compact array of 36 UK FATIMA LaBr3 detectors is designed based on efficiency studies with Geant4. The photo peak efficiency in the region of interest compares to other gamma detection systems used in this field. The features of the internal decay of 138La is used in a background study to obtain an online calibration of the gamma detectors. Background data are fit to the Monte Carlo model of the self activity assuming crude exponential behavior of external background. Accuracy in the region of interest is of the order of some keV in this first study

Working Memory and Response Inhibition as One Integral Phenotype of Adult ADHD? A Behavioral and Imaging Correlational Investigation

Objective: It is an open question whether working memory (WM) and response inhibition (RI) constitute one integral phenotype in attention deficit hyperactivity disorder (ADHD). Method: The authors investigated 45 adult ADHD patients and 41 controls comparable for age, gender, intelligence, and education during a letter n-back and a stop-signal task, and measured prefrontal oxygenation by means of functional near-infrared spectroscopy. Results: The authors replicated behavioral and cortical activation deficits in patients compared with controls for both tasks and also for performance in both control conditions. In the patient group, 2-back performance was correlated with stop-signal reaction time. This correlation did not seem to be specific for WM and RI as 1-back performance was correlated with go reaction time. No significant correlations of prefrontal oxygenation between WM and RI were found. Conclusion: The authors' findings do not support the hypothesis of WM and RI representing one integral phenotype of ADHD mediated by the prefrontal cortex

Understanding drugs in breast cancer through drug sensitivity screening

With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between

Ovarian cancer cell line panel (OCCP): Clinical importance of in vitro morphological subtypes

Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological a

Fusion Hindrance and Pauli Blocking in 58Ni + 64Ni

58Ni +64Ni is the first case where the influence of positive Q-value transfer channels on sub-barrier fusion was evidenced, in a very well known experiment by Beckerman et al., by comparing with the two systems 58Ni + 58Ni and 64Ni+64Ni. Subsequent measurements on 64Ni + 64Ni showed that fusion hindrance is clearly present in this case. On the other hand, no indication of hindrance can be observed for 58Ni + 64Ni down to the measured level of 0.1 mb. In the present experiment the excitation function has been extended by two orders of magnitude downward. The cross sections for 58Ni + 64Ni continue decreasing very smoothly below the barrier, down to '1 µb. The logarithmic slope of the excitation function increases slowly, showing a tendency to saturate at the lowest energies. No maximum of the astrophysical S -factor is observed. Coupled-channels (CC) calculations using a Woods-Saxon potential and includinginelastic excitations only, underestimate the sub-barrier cross sections by a large amount. Good agreement is found by adding two-neutron transfer couplings to a schematical level. This behaviour is quite different from what already observed for 64Ni+ 64Ni (no positive Q-value transfer channels available), where a clear low-energy maximum of the S -factorappears, and whose excitation function is overestimated by a standard Woods-Saxon CC calculation. No hindrance effect is observed in 58Ni+ 64Ni in the measured energy range. This trend at deep sub-barrier energies reinforces the recent suggestion that the availability of several states following transfer with Q>0, effectively counterbalances the Pauli repulsion that, in general, is predicted to reduce tunneling probability inside the Coulomb barrier

Working Memory and Response Inhibition as One Integral Phenotype of Adult ADHD? A Behavioral and Imaging Correlational Investigation

Objective: It is an open question whether working memory (WM) and response inhibition (RI) constitute one integral phenotype in attention deficit hyperactivity disorder (ADHD). Method: The authors investigated 45 adult ADHD patients and 41 controls comparable for age, gender, intelligence, and education during a letter n-back and a stop-signal task, and measured prefrontal oxygenation by means of functional near-infrared spectroscopy. Results: The authors replicated behavioral and cortical activation deficits in patients compared with controls for both tasks and also for performance in both control conditions. In the patient group, 2-back performance was correlated with stop-signal reaction time. This correlation did not seem to be specific for WM and RI as 1-back performance was correlated with go reaction time. No significant correlations of prefrontal oxygenation between WM and RI were found. Conclusion: The authors' findings do not support the hypothesis of WM and RI representing one integral phenotype of ADHD mediated by the prefrontal cortex

MicroRNAs as possible indicators of drug sensitivity in breast cancer cell lines

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. In this way they might influence whether a cell is sensitive or resistant to a certain drug. So far, only a limited number of relatively small scale studies comprising few cell lines and/or drugs have been performed. To obtain a broader view on miRNAs and their association with drug response, we investigated the expression levels of 411 miRNAs in relation to drug sensitivity in 36 breast cancer cell lines. For this purpose IC50 values of a drug screen involving 34 drugs were associated with miRNA expression data of the same breast cancer cell lines. Since molecular subtype of the breast cancer cell lines is considered a confounding factor in drug association studies, multivariate analysis taking subtype into account was performed on significant miRNA-drug associations which retained 13 associations. These associations consisted of 11 different miRNAs and eight different drugs (among which Paclitaxel, Docetaxel and Veliparib). The taxanes, Paclitaxel and Docetaxel, were the only drugs having miRNAs in common: hsa-miR-187-5p and hsa-miR-106a-3p indicative of drug resistance while Paclitaxel sensitivity alone associated with hsa-miR-556-5p. Tivantinib was associated with hsalet-7d-5p and hsa-miR-18a-5p for sensitivity and hsa-miR-637 for resistance. Drug sensitivity was associated with hsa-let-7a-5p for Bortezomib, hsa-miR-135a-3p for JNJ-707 and hsa-miR-185-3p for Panobinostat. Drug resistance was associated with hsa-miR-182-5p for Veliparib and hsa-miR-629-5p for Tipifarnib. Pathway analysis for significant miRNAs was performed to reveal biological roles, aiding to find a potential mechanistic link for the observed associations with drug response. By doing so hsa-miR-187-5p was linked to the cell cycle G2-M checkpoint in line with this checkpoint being the target of taxanes. In conclusion, our study shows that miRNAs could potentially serve as biomarkers for intrinsic drug resistance and that pathway analyses can provide additional information in this contex

MiRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs

Introduction: Breast cancer is a genetically and phenotypically complex disease. To understand the role of miRNAs in this molecular complexity, we performed miRNA expression analysis in a cohort of molecularly well-characterized human breast cancer cell lines to identify miRNAs associated with the most common molecular subtypes and the most frequent genetic aberrations. Methods: Using a microarray carrying LNA™ modified oligonucleotide capture probes), expression levels of 725 human miRNAs were measured in 51 breast cancer cell lines. Differential miRNA expression was explored by unsupervised cluster analysis and was then associated with the molecular subtypes and genetic aberrations commonly present in breast cancer. Results: Unsupervised cluster analysis using the most variably expressed miRNAs divided the 51 breast cancer cell lines into a major and a minor cluster predominantly mirroring the luminal and basal intrinsic subdivision of breast cancer cell lines. One hundred and thirteen miRNAs were differentially expressed between these two main clusters. Forty miRNAs were differentially expressed between basal-like and normal-like/claudin-low cell lines. Within the luminal-group, 39 miRNAs were associated with ERBB2 overexpression and 24 with E-cadherin gene mutations, which are frequent in this subtype of breast cancer cell lines. In contrast, 31 miRNAs were associated with E-cadherin promoter hypermethylation, which, contrary to E-cadherin mutation, is exclusively observed in breast cancer cell lines that are not of luminal origin. Thirty miRNAs were associated with p16INK4 status while only a fe

A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity.

Our knowledge about the gut microbiota of pigs is still scarce, despite the importance of these animals for biomedical research and agriculture. Here, we present a collection of cultured bacteria from the pig gut, including 110 species across 40 families and nine phyla. We provide taxonomic descriptions for 22 novel species and 16 genera. Meta-analysis of 16S rRNA amplicon sequence data and metagenome-assembled genomes reveal prevalent and pig-specific species within Lactobacillus, Streptococcus, Clostridium, Desulfovibrio, Enterococcus, Fusobacterium, and several new genera described in this study. Potentially interesting functions discovered in these organisms include a fucosyltransferase encoded in the genome of the novel species Clostridium porci, and prevalent gene clusters for biosynthesis of sactipeptide-like peptides. Many strains deconjugate primary bile acids in in vitro assays, and a Clostridium scindens strain produces secondary bile acids via dehydroxylation. In addition, cells of the novel species Bullifex porci are coccoidal or spherical under the culture conditions tested, in contrast with the usual helical shape of other members of the family Spirochaetaceae. The strain collection, called 'Pig intestinal bacterial collection' (PiBAC), is publicly available at www.dsmz.de/pibac and opens new avenues for functional studies of the pig gut microbiota