New multiple matched filter: design and experimental realization

A method of making a multiple matched filter which allows the recognition of different characters in successive planes in simple conditions is proposed. The generation of the filter is based on recording on the same plate the Fourier transforms of the different patterns to be recognized, each of which is affected by different spherical phase factors because the patterns have been placed at different distances from the lens. This is proved by means of experiments with a triple filter which allows satisfactory recognition of three characters.

Lenalidomide maintenance after stem-cell transplantation for multiple myeloma.

BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebo-controlled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation. METHODS: We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival. RESULTS: Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P<0.001). This benefit was observed across all patient subgroups, including those based on the β(2)-microglobulin level, cytogenetic profile, and response after transplantation. With a median follow-up period of 45 months, more than 70% of patients in both groups were alive at 4 years. The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups. The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group (P=0.002). Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001). CONCLUSIONS: Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.).

Roles of multiple acyl-CoA oxidases in the routing of carbon flow towards β-oxidation and polyhydroxyalkanoate biosynthesis in Yarrowia lipolytica.

The oleaginous yeast Yarrowia lipolytica possesses six acyl-CoA oxidase (Aox) isoenzymes encoded by genes POX1-POX6. The respective roles of these multiple Aox isoenzymes were studied in recombinant Y. lipolytica strains that express heterologous polyhydroxyalkanoate (PHA) synthase (phaC) of Pseudomonas aeruginosa in varying POX genetic backgrounds, thus allowing assessment of the impact of specific Aox enzymes on the routing of carbon flow to β-oxidation or to PHA biosynthesis. Analysis of PHA production yields during growth on fatty acids with different chain lengths has revealed that the POX genotype significantly affects the PHA levels, but not the monomer composition of PHA. Aox3p function was found to be responsible for 90% and 75% of the total PHA produced from either C9:0 or C13:0 fatty acid, respectively, whereas Aox5p encodes the main Aox involved in the biosynthesis of 70% of PHA from C9:0 fatty acid. Other Aoxs, such as Aox1p, Aox2p, Aox4p and Aox6p, were not found to play a significant role in PHA biosynthesis, independent of the chain length of the fatty acid used. Finally, three known models of β-oxidation are discussed and it is shown that a 'leaky-hose pipe model' of the cycle can be applied to Y. lipolytica.

Models that include supercoiling of topological domains reproduce several known features of interphase chromosomes.

Understanding the structure of interphase chromosomes is essential to elucidate regulatory mechanisms of gene expression. During recent years, high-throughput DNA sequencing expanded the power of chromosome conformation capture (3C) methods that provide information about reciprocal spatial proximity of chromosomal loci. Since 2012, it is known that entire chromatin in interphase chromosomes is organized into regions with strongly increased frequency of internal contacts. These regions, with the average size of ∼1 Mb, were named topological domains. More recent studies demonstrated presence of unconstrained supercoiling in interphase chromosomes. Using Brownian dynamics simulations, we show here that by including supercoiling into models of topological domains one can reproduce and thus provide possible explanations of several experimentally observed characteristics of interphase chromosomes, such as their complex contact maps.

Global phylogenomic analysis of nonencapsulated Streptococcus pneumoniae reveals a deep-branching classic lineage that is distinct from multiple sporadic lineages.

The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated S. pneumoniae (non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if non-Ec-Sp evolve sporadically, if they have high antibiotic nonsusceptiblity rates and a unique, specific gene content. Here, whole-genome sequencing of 131 non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multilocus sequences types (STs) ST344 (n = 39) and ST448 (n = 40). All ST344 and nine ST448 isolates had high nonsusceptiblity rates to β-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to human epithelial cells (P = 0.005). In contrast, sporadic non-Ec-Sp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of PCV, non-Ec-Sp may become more prevalent.

Maintenance therapy with thalidomide improves survival in patients with multiple myeloma.

Newer chemotherapeutic protocols as well as high-dose chemotherapy have increased the response rate in myeloma. However, these treatments are not curative. Effective maintenance strategies are now required to prolong the duration of response. We conducted a randomized trial of maintenance treatment with thalidomide and pamidronate. Two months after high-dose therapy, 597 patients younger than age 65 years were randomly assigned to receive no maintenance (arm A), pamidronate (arm B), or pamidronate plus thalidomide (arm C). A complete or very good partial response was achieved by 55% of patients in arm A, 57% in arm B, and 67% in arm C (P = .03). The 3-year postrandomization probability of event-free survival was 36% in arm A, 37% in arm B, and 52% in arm C (P < .009). The 4-year postdiagnosis probability of survival was 77% in arm A, 74% in arm B, and 87% in arm C (P < .04). The proportion of patients who had skeletal events was 24% in arm A, 21% in arm B, and 18% in arm C (P = .4). Thalidomide is an effective maintenance therapy in patients with multiple myeloma. Maintenance treatment with pamidronate does not decrease the incidence of bone events.

Multiple Geotechnological Tools Applied to Digital Mapping of Tropical Soils

ABSTRACT In recent years, geotechnologies as remote and proximal sensing and attributes derived from digital terrain elevation models indicated to be very useful for the description of soil variability. However, these information sources are rarely used together. Therefore, a methodology for assessing and specialize soil classes using the information obtained from remote/proximal sensing, GIS and technical knowledge has been applied and evaluated. Two areas of study, in the State of São Paulo, Brazil, totaling approximately 28.000 ha were used for this work. First, in an area (area 1), conventional pedological mapping was done and from the soil classes found patterns were obtained with the following information: a) spectral information (forms of features and absorption intensity of spectral curves with 350 wavelengths -2,500 nm) of soil samples collected at specific points in the area (according to each soil type); b) obtaining equations for determining chemical and physical properties of the soil from the relationship between the results obtained in the laboratory by the conventional method, the levels of chemical and physical attributes with the spectral data; c) supervised classification of Landsat TM 5 images, in order to detect changes in the size of the soil particles (soil texture); d) relationship between classes relief soils and attributes. Subsequently, the obtained patterns were applied in area 2 obtain pedological classification of soils, but in GIS (ArcGIS). Finally, we developed a conventional pedological mapping in area 2 to which was compared with a digital map, ie the one obtained only with pre certain standards. The proposed methodology had a 79 % accuracy in the first categorical level of Soil Classification System, 60 % accuracy in the second category level and became less useful in the categorical level 3 (37 % accuracy).

Multiple sulfatase deficiency with neonatal manifestation.

Multiple Sulfatase Deficiency (MSD; OMIM 272200) is a rare autosomal recessive inborn error of metabolism caused by mutations in the sulfatase modifying factor 1 gene, encoding the formyglycine-generating enzyme (FGE), and resulting in tissue accumulation of sulfatides, sulphated glycosaminoglycans, sphingolipids and steroid sulfates. Less than 50 cases have been published so far. We report a new case of MSD presenting in the newborn period with hypotonia, apnoea, cyanosis and rolling eyes, hepato-splenomegaly and deafness. This patient was compound heterozygous for two so far undescribed SUMF1 mutations (c.191C¿>¿A; p.S64X and c.818A¿>¿G; p.D273G).

Respiratory chain dysfunction associated with multiple mitochondrial DNA deletions in antiretroviral therapy-related lipodystrophy.

Highly-active antiretroviral therapy (HAART) can induce a characteristic lipodystrophy syndrome characterized by peripheral fat wasting and central adiposity, usually associated with hyperlipidaemia and insulin resistance [1,2]. Indirect data have led some authors to propose that mitochondrial dysfunction could play a role in this syndrome [3,4].To date, as recently outlined by Kakuda et al. [5] in this journal, HIV-infected patients developing lipodystrophy have not been studied for mitochondrial changes or respiratory chain capacity...

Contribution of (sub)domains of Staphylococcus aureus fibronectin-binding protein to the proinflammatory and procoagulant response of human vascular endothelial cells.

The Staphylococcus aureus fibronectin (Fn) -binding protein A (FnBPA) is involved in bacterium-endothelium interactions which is one of the crucial events leading to infective endocarditis (IE). We previously showed that the sole expression of S. aureus FnBPA was sufficient to confer to non-invasive Lactococcus lactis bacteria the capacity to invade human endothelial cells (ECs) and to launch the typical endothelial proinflammatory and procoagulant responses that characterize IE. In the present study we further questioned whether these bacterium-EC interactions could be reproduced by single or combined FnBPA sub-domains (A, B, C or D) using a large library of truncated FnBPA constructs expressed in L. lactis. Significant invasion of cultured ECs was found for L. lactis expressing the FnBPA subdomains CD (aa 604-877) or A4(+16) (aa 432-559). Moreover, this correlates with the capacity of these fragments to elicit in vitro a marked increase in EC surface expression of both ICAM-1 and VCAM-1 and secretion of the CXCL8 chemokine and finally to induce a tissue factor-dependent endothelial coagulation response. We thus conclude that (sub)domains of the staphylococcal FnBPA molecule that express Fn-binding modules, alone or in combination, are sufficient to evoke an endothelial proinflammatory as well as a procoagulant response and thus account for IE severity.

Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis

Epstein-Barr virus (EBV) has been associated with multiple sclerosis (MS), however, most studies examining the relationship between the virus and the disease have been based on serologies, and if EBV is linked to MS, CD8+ T cells are likely to be involved as they are important both in MS pathogenesis and in controlling viruses. We hypothesized that valuable information on the link between MS and EBV would be ascertained from the study of frequency and activation levels of EBV-specific CD8+ T cells in different categories of MS patients and control subjects. We investigated EBV-specific cellular immune responses using proliferation and enzyme linked immunospot assays, and humoral immune responses by analysis of anti-EBV antibodies, in a cohort of 164 subjects, including 108 patients with different stages of MS, 35 with other neurological diseases and 21 healthy control subjects. Additionally, the cohort were all tested against cytomegalovirus (CMV), another neurotropic herpes virus not convincingly associated with MS, nor thought to be deleterious to the disease. We corrected all data for age using linear regression analysis over the total cohorts of EBV- and CMV-infected subjects. In the whole cohort, the rate of EBV and CMV infections were 99% and 51%, respectively. The frequency of IFN-gamma secreting EBV-specific CD8+ T cells in patients with clinically isolated syndrome (CIS) was significantly higher than that found in patients with relapsing-remitting MS (RR-MS), secondary-progressive MS, primary-progressive MS, patients with other neurological diseases and healthy controls. The shorter the interval between MS onset and our assays, the more intense was the EBV-specific CD8+ T-cell response. Confirming the above results, we found that EBV-specific CD8+ T-cell responses decreased in 12/13 patients with CIS followed prospectively for 1.0 +/- 0.2 years. In contrast, there was no difference between categories for EBV-specific CD4+ T cell, or for CMV-specific CD4+ and CD8+ T-cell responses. Anti-EBV-encoded nuclear antigen-1 (EBNA-1)-specific antibodies correlated with EBV-specific CD8+ T cells in patients with CIS and RR-MS. However, whereas EBV-specific CD8+ T cells were increased the most in early MS, EBNA-1-specific antibodies were increased in early as well as in progressive forms of MS. Our data show high levels of CD8+ T-cell activation against EBV--but not CMV--early in the course of MS, which support the hypothesis that EBV might be associated with the onset of this disease.

Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse

The reelin gene encodes an extracellular protein that is crucial for neuronal migration in laminated brain regions. To gain insights into the functions of Reelin, we performed high-resolution in situ hybridization analyses to determine the pattern of reelin expression in the developing forebrain of the mouse. We also performed double-labeling studies with several markers, including calcium-binding proteins, GAD65/67, and neuropeptides, to characterize the neuronal subsets that express reelin transcripts. reelinexpression was detected at embryonic day 10 and later in the forebrain, with a distribution that is consistent with the prosomeric model of forebrain regionalization. In the diencephalon, expression was restricted to transverse and longitudinal domains that delineated boundaries between neuromeres. During embryogenesis,reelin was detected in the cerebral cortex in Cajal-Retzius cells but not in the GABAergic neurons of layer I. At prenatal stages, reelin was also expressed in the olfactory bulb, and striatum and in restricted nuclei in the ventral telencephalon, hypothalamus, thalamus, and pretectum. At postnatal stages, reelin transcripts gradually disappeared from Cajal-Retzius cells, at the same time as they appeared in subsets of GABAergic neurons distributed throughout neocortical and hippocampal layers. In other telencephalic and diencephalic regions,reelin expression decreased steadily during the postnatal period. In the adult, there was prominent expression in the olfactory bulb and cerebral cortex, where it was restricted to subsets of GABAergic interneurons that co-expressed calbindin, calretinin, neuropeptide Y, and somatostatin. This complex pattern of cellular and regional expression is consistent with Reelin having multiple roles in brain development and adult brain function.