Effects of Sequence Disorder on DNA Looping and Cyclization

Effects of sequence disorder on looping and cyclization of the double-stranded DNA are studied theoretically. Both random intrinsic curvature and inhomogeneous bending rigidity are found to result in a remarkably wide distribution of cyclization probabilities. For short DNA segments, the range of the distribution reaches several orders of magnitude for even completely random sequences. The ensemble averaged values of the cyclization probability are also calculated, and the connection to the recent experiments is discussed.Comment: 8 pages, 4 figures, LaTeX; accepted to Physical Review E; v2: a substantially revised version; v3: references added, conclusions expanded, minor editorial corrections to the text; v4: a substantially revised and expanded version (total number of pages doubled); v5: new Figure 4, captions expanded, minor editorial improvements to the tex

From Golden Spirals to Constant Slope Surfaces

In this paper, we find all constant slope surfaces in the Euclidean 3-space, namely those surfaces for which the position vector of a point of the surface makes constant angle with the normal at the surface in that point. These surfaces could be thought as the bi-dimensional analogue of the generalized helices. Some pictures are drawn by using the parametric equations we found.Comment: 11 pages, 8 figure

Development of a diagnostic rule for identifying radiographic osteoarthritis in people with first metatarsophalangeal joint pain

SummaryObjectiveTo develop a diagnostic rule for the identification of radiographic osteoarthritis (OA) of the first metatarsophalangeal joint (MTPJ) in people with first MTPJ pain.DesignSymptoms and clinical observations were documented in 181 people with first MTPJ pain, and the presence of OA was confirmed using plain film radiography. Diagnostic test statistics were calculated to assess the ability of symptoms and clinical observations to identify radiographic OA. Multivariate logistic regression was used to develop two diagnostic models: a statistically optimal model and a simplified clinical model.ResultsMultivariate logistic regression identified pain duration greater than 25 months, the presence of a dorsal exostosis, hard-end feel, crepitus and less than 64° of first MTPJ dorsiflexion to be significantly associated with radiographic OA. The statistically optimal model and clinical model performed similarly, with the areas under the receiver operating characteristics curves being 0.87 (95% confidence interval [CI] 0.81–0.93) and 0.87 (95% CI 0.80–0.93), respectively, and the percentage of cases correctly classified being 86.2 and 85.6, respectively. A cut-off score of ≥3 using the clinical model resulted in a sensitivity of 88%, specificity of 71%, accuracy of 84%, positive likelihood ratio of 3.07 and negative likelihood ratio of 0.17.ConclusionsIn people with first MTPJ pain, a model consisting of five clinical observations can accurately identify the presence or absence of radiographic OA. The application of this diagnostic rule may assist clinical decision making and potentially reduce the need for referral for radiographs

Human synthetic lethal inference as potential anti-cancer target gene detection

Background: Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods. Results: In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes) in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases) as well as on existent approved drugs (DrugBank database) supports our selection of cancer-therapy candidates./nConclusions: Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology

Frontal brain metastasis of amelanotic malignant melanoma: Case presentation

Amelanotic melanoma is met only in 2-8% of cases with malignant melanoma. The incidence of brain metastases in patients with malignant melanoma ranges from 6-43% of cases. Brain metastases are frequently associated with malignant melanoma after the intratumorale hemorrhage. We choose to present the case of 58-years-old men with a frontal brain metastasis of amelanotic malignant melanoma

Proton and alpha radiation-induced mutational profiles in human cells

Ionizing radiation is known to be DNA damaging and mutagenic, however less is known about which mutational footprints result from exposures of human cells to different types of radiation. We were interested in the mutagenic effects of particle radiation exposures on genomes of various human cell types, in order to gauge the genotoxic risks of galactic cosmic radiation, and of certain types of tumor radiotherapy. To this end, we exposed cultured cell lines from the human blood, breast and lung to fractionated proton and alpha particle (helium nuclei) beams at doses sufficient to considerably affect cell viability. Whole-genome sequencing revealed that mutation rates were not overall markedly increased upon proton and alpha exposures. However, there were modest changes in mutation spectra and distributions, such as the increases in clustered mutations and of certain types of indels and structural variants. The spectrum of mutagenic effects of particle beams may be cell-type and/or genetic background specific. Overall, the mutational effects of repeated exposures to proton and alpha radiation on human cells in culture appear subtle, however further work is warranted to understand effects of long-term exposures on various human tissues.© 2023. The Author(s)

The Carina dSph galaxy: where is the edge?

Recent cosmological N-body simulations suggest that current empirical estimates of tidal radii in dSphs might be underestimated by at least one order of magnitude. To constrain the plausibility of this theoretical framework, we undertook a multiband (U,B,V,I) survey of the Carina dSph. Deep B,V data of several fields located at radial distances from the Carina center ranging from 0.5 to 4.5 degrees show a sizable sample of faint blue objects with the same magnitudes and colors of old, Turn-Off stars detected across the center. We found that the (U-V,B-I) color-color plane is a robust diagnostic to split stars from background galaxies. Unfortunately, current U,I-band data are too shallow to firmly constrain the real extent of Carina.Comment: To be published on the proceedings of the XLIX meeting of the Italian Astronomical Society. Requires mem.cl