Selective labeling: identifying representative sub-volumes for interactive segmentation

Automatic segmentation of challenging biomedical volumes with multiple objects is still an open research field. Automatic approaches usually require a large amount of training data to be able to model the complex and often noisy appearance and structure of biological organelles and their boundaries. However, due to the variety of different biological specimens and the large volume sizes of the datasets, training data is costly to produce, error prone and sparsely available. Here, we propose a novel Selective Labeling algorithm to overcome these challenges; an unsupervised sub-volume proposal method that identifies the most representative regions of a volume. This massively-reduced subset of regions are then manually labeled and combined with an active learning procedure to fully segment the volume. Results on a publicly available EM dataset demonstrate the quality of our approach by achieving equivalent segmentation accuracy with only 5 % of the training data

Diffusive propagation of cosmic rays from supernova remnants in the Galaxy. II: anisotropy

We investigate the effects of stochasticity in the spatial and temporal distribution of supernova remnants on the anisotropy of cosmic rays observed at Earth. The calculations are carried out for different choices of the diffusion coefficient D(E) for propagation in the Galaxy. The propagation and spallation of nuclei are taken into account. At high energies we assume that $D(E)\sim(E/Z)^{\delta}$, with $\delta=1/3$ and $\delta=0.6$ being the reference scenarios. The large scale distribution of supernova remnants in the Galaxy is modeled following the distribution of pulsars with and without accounting for the spiral structure of the Galaxy. Our calculations allow us to determine the contribution to anisotropy resulting from both the large scale distribution of SNRs in the Galaxy and the random distribution of the nearest remnants. The naive expectation that the anisotropy amplitude scales as D(E) is shown to be an oversimplification which does not reflect in the predicted anisotropy for any realistic distribution of the sources. The fluctuations in the anisotropy pattern are dominated by nearby sources, so that predicting or explaining the observed anisotropy amplitude and phase becomes close to impossible. We find however that the very weak energy dependence of the anisotropy amplitude below $10^{5}$ GeV and the rise at higher energies, can best be explained if the diffusion coefficient is $D(E)\sim E^{1/3}$. Faster diffusion, for instance with $\delta=0.6$, leads in general to an exceedingly large anisotropy amplitude. The spiral structure introduces interesting trends in the energy dependence of the anisotropy pattern, which qualitatively reflect the trend seen in the data. For large values of the halo size we find that the anisotropy becomes dominated by the large scale regular structure of the source distribution, leading indeed to a monotonic increase of $\delta_A$ with energy.Comment: 21 Pages, to appear in JCA

Metformin:A Narrative Review of Its Potential Benefits for Cardiovascular Disease, Cancer and Dementia

The biguanide metformin has been used as first-line therapy in type 2 diabetes mellitus (T2DM) treatment for several decades. In addition to its glucose-lowering properties and its prevention of weight gain, the landmark UK Prospective Diabetes Study (UKPDS) demonstrated cardioprotective properties in obese T2DM patients. Coupled with a favorable side effect profile and low cost, metformin has become the cornerstone in the treatment of T2DM worldwide. In addition, metformin is increasingly being investigated for its potential anticancer and neuroprotective properties both in T2DM patients and non-diabetic individuals. In the meantime, new drugs with powerful cardioprotective properties have been introduced and compete with metformin for its place in the treatment of T2DM. In this review we will discuss actual insights in the various working mechanisms of metformin and the evidence for its beneficial effects on (the prevention of) cardiovascular disease, cancer and dementia. In addition to observational evidence, emphasis is placed on randomized trials and recent meta-analyses to obtain an up-to-date overview of the use of metformin in clinical practice

Comparison of the RNA-amplification based methods RT–PCR and NASBA for the detection of circulating tumour cells

Increasingly, reverse transcriptase polymerase chain reaction (RT–PCR) is used to detect clinically significant tumour cells in blood or bone marrow. This may result in a redefinition of disease-free and clinical relapse. However, its clinical utility may be limited by lack of automation or reproducibility. Recent studies have suggested nucleic acid sequence-based amplification of target RNA may be more robust. In this study, nucleic acid sequence-based amplification was established to detect melanoma, colorectal and prostate cancer cells. Nucleic acid sequence-based amplification and RT–PCR both successfully amplified target RNA in peripheral blood samples from patients with melanoma and colorectal cancer, but only RT–PCR detected PSA in blood samples from patients with prostate cancer. There was relatively good agreement between sample replicates analyzed by RT–PCR (Kappa values of one for tyrosinase, 0.67 for CK-20 and one for PSA), but less agreement when analyzed by nucleic acid sequence-based amplification. This may limit the routine use of NASBA for the detection of clinically significant disease. In summary, RT–PCR appears at present to be the most reliable and reproducible method for the detection of low-level disease in cancer patients, although prospective studies are warranted to assess the clinical utility of different molecular diagnostic methods

Swine Influenza A Outbreak, Fort Dix, New Jersey, 1976

Published literature and events surrounding the outbreak are reviewed

Changes in active site histidine hydrogen bonding trigger cryptochrome activation

Cryptochrome (CRY) is the principal light sensor of the insect circadian clock. Photoreduction of the Drosophila CRY (dCRY) flavin cofactor to the anionic semiquinone (ASQ) restructures a C-terminal tail helix (CTT) that otherwise inhibits interactions with targets that include the clock protein Timeless (TIM). All-atom molecular dynamics (MD) simulations indicate that flavin reduction destabilizes the CTT, which undergoes large-scale conformational changes (the CTT release) on short (25 ns) timescales. The CTT release correlates with the conformation and protonation state of conserved His378, which resides between the CTT and the flavin cofactor. Poisson-Boltzmann calculations indicate that flavin reduction substantially increases the His378 pKa. Consistent with coupling between ASQ formation and His378 protonation, dCRY displays reduced photoreduction rates with increasing pH; however, His378Asn/Arg variants show no such pH dependence. Replica-exchange MD simulations also support CTT release mediated by changes in His378 hydrogen bonding and verify other responsive regions of the protein previously identified by proteolytic sensitivity assays. His378 dCRY variants show varying abilities to light-activate TIM and undergo self-degradation in cellular assays. Surprisingly, His378Arg/Lys variants do not degrade in light despite maintaining reactivity toward TIM, thereby implicating different conformational responses in these two functions. Thus, the dCRY photosensory mechanism involves flavin photoreduction coupled to protonation of His378, whose perturbed hydrogen-bonding pattern alters the CTT and surrounding regions