2,073 research outputs found
Developing a victorious strategy to the second strong gravitational lensing data challenge
Strong lensing is a powerful probe of the matter distribution in galaxies and clusters and a relevant tool for cosmography. Analyses of strong gravitational lenses with deep learning have become a popular approach due to these astronomical objects’ rarity and image complexity. Next-generation surveys will provide more opportunities to derive science from these objects and an increasing data volume to be analysed. However, finding strong lenses is challenging, as their number densities are orders of magnitude below those of galaxies. Therefore, specific strong lensing search algorithms are required to discover the highest number of systems possible with high purity and low false alarm rate. The need for better algorithms has prompted the development of an open community data science competition named strong gravitational lensing challenge (SGLC). This work presents the deep learning strategies and methodology used to design the highest scoring algorithm in the second SGLC (II SGLC). We discuss the approach used for this data set, the choice of a suitable architecture, particularly the use of a network with two branches to work with images in different resolutions, and its optimization. We also discuss the detectability limit, the lessons learned, and prospects for defining a tailor-made architecture in a survey in contrast to a general one. Finally, we release the models and discuss the best choice to easily adapt the model to a data set representing a survey with a different instrument. This work helps to take a step towards efficient, adaptable, and accurate analyses of strong lenses with deep learning frameworks
IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia
IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in both childhood and adult B-cell precursor acute lymphoblastic leukemia (B-ALL). Previously, we revealed that COBL is a hotspot for breakpoints in leukemia and could promote IKZF1 deletions. Through an international collaboration, we provide a detailed genetic and clinical picture of B-ALL with COBL rearrangements (COBL-r). Patients with B-ALL and IKZF1 deletion (n = 133) were included. IKZF1 ∆1-8 were associated with large alterations within chromosome 7: monosomy 7 (18%), isochromosome 7q (10%), 7p loss (19%), and interstitial deletions (53%). The latter included COBL-r, which were found in 12% of the IKZF1 ∆1-8 cohort. Patients with COBL-r are mostly classified as intermediate cytogenetic risk and frequently harbor ETV6, PAX5, CDKN2A/B deletions. Overall, 56% of breakpoints were located within COBL intron 5. Cryptic recombination signal sequence motifs were broadly distributed within the sequence of COBL, and no enrichment for the breakpoint cluster region was found. In summary, a diverse spectrum of alterations characterizes ΔIKZF1 and they also include deletion breakpoints within COBL. We confirmed that COBL is a hotspot associated with ΔIKZF1, but these rearrangements are not driven by RAG-mediated recombination
Potent and Broad-Spectrum Antimicrobial Activity of Analogs from the Scorpion Peptide Stigmurin
Scorpion venom constitutes a rich source of biologically active compounds with high potential for therapeutic and biotechnological applications that can be used as prototypes for the design of new drugs. The aim of this study was to characterize the structural conformation, evaluate the antimicrobial activity, and gain insight into the possible action mechanism underlying it, for two new analog peptides of the scorpion peptide Stigmurin, named StigA25 and StigA31. The amino acid substitutions in the native sequence for lysine residues resulted in peptides with higher positive net charge and hydrophobicity, with an increase in the theoretical helical content. StigA25 and StigA31 showed the capacity to modify their structural conformation according to the environment, and were stable to pH and temperature variation-results similar to the native peptide. Both analog peptides demonstrated broad-spectrum antimicrobial activity in vitro, showing an effect superior to that of the native peptide, being non-hemolytic at the biologically active concentrations. Therefore, this study demonstrates the therapeutic potential of the analog peptides from Stigmurin and the promising approach of rational drug design based on scorpion venom peptide to obtain new anti-infective agents.publishersversionpublishe
Immunocytochemical expression of p16 INK4A and Ki-67 in cytologically negative and equivocal pap smears positive for oncogenic human papillomavirus
This study was designed to analyze the cross-sectional comparison of the
p16
INK4A
and Ki-67 immunocytochemical expression in negative and equivocal (atyp-ical
squamous cells of undetermined significance (ASC-US)) liquid-based cytology
(LBC) samples testing positive for high-risk human papillomavirus (HPV) types with
HC2 assay or polymerase-chain reaction (PCR). A series of 199 consecutive LBC speci-mens
derived from the same number of women participating in the ongoing Latin American
Screening Study at Leonor Mendes de Barros Hospital, São Paulo, were analyzed
using immunocytochemistry for expression of p16
INK4A
and Ki-67 in negative and
equivocal LBC samples testing positive for high-risk HPV types with hybrid capture
II test (HC2) or PCR. All patients with at least one test positive (cytology, PCR, and/or
HC2) were followed each 6 months for 3 years. The follow-up procedure consisted of
visual examination, colposcopic inspection, cytology, and HC2 assay. Among the neg-ative
cytologic samples, 101 were HPV-positive and 55 HPV-negative. Of the HPV-pos-itive
group, 59 of 101 cases (58.4%) were positive for both p16 and Ki67
immunostaining, and 17 of 101 (16.8%) were negative for both. The proportion of
Ki-67-positivity increased almost in parallel with the increasing grade of p16-positivity
(p = 0.0001 for linear trend). In the HPV-negative group, both markers were negative in
41 of 55 cases (74.5%), and no statistical relationship was observed between the two
markers (Pearson, p = 0.595). HPV-positive ASC-US samples demonstrated a simulta-neous
positive immunoreaction for p16 and Ki67 in 11 of 16 cases (68.7%), whereas 3
(18.7%) were concurrently negative. The relationship between the two markers was of
borderline significance (Pearson, p = 0.053), but no linear relationship was found be-tween
the graded p16 and Ki-67 expression (p = 0.065 for linear trend). In the HPV-negative
ASC-US group, there was no statistical association between the graded p16
and Ki-67 positivity (Pearson, p = 0.281). After 36 months of follow-up of the ASC-US
patients, 6 women still displayed ASC-US smear, of which 4 of 6 were HPV-positive
and expressed both p16 and Ki-67 markers. Two of 43 ASC-US smears had high-grade squamous intraepithelial lesions diagnosed (4.6%), and 1 had low-grade squamous
intraepithelial lesion (2.3%). All of those were positive for HPV, p16 and Ki-67. Patients
with ASC-US diagnosis and positive high-risk HPV status and positive for p16
INK4A
Ki67 should be carefully observed to exclude occurrence of a squamous intraepithelial
lesion. The combination of these two markers can be a useful implement for manage-ment
of women with equivocal cytology.European Commission (EC) - INCO-DEV Programme - Project #ICA4-CT-2001-10013
Genotyping of two Neisseria gonorrhoeae fluroquinolone-resistant strains in the Brazilian Amazon Region
We report two ciprofloxacin and ofloxacin-resistant Neisseria gonorrhoeae strains that were isolated from the urethral discharge of male patients at the sexually transmitted diseases outpatient clinic of the Alfredo da Matta Foundation (Manaus, state of Amazonas, Brazil). The gonococci displayed minimal inhibitory concentrations (> 32.00 µg/mL) and three mutations in the quinolone resistance-determining region (S91F and D95G in GyrA and S87R in ParC). Both isolates were genotyped using N. gonorrhoeae multi-antigen sequence typing and the analysis showed that the ST225 which represented an emerging widespread multi-resistant clone that has also been associated with reduced susceptibility to ceftriaxone. We recommend continued surveillance of this pathogen to assess the efficacy of anti-gonococcal antibiotics in Brazil
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