A concentric morphology model for the detection of masses in mammography

We propose a technique for the automated detection of malignant masses in screening mammography. The technique is based on the presence of concentric layers surrounding a focal area with suspicious morphological characteristics and low relative incidence in the breast region. Mammographic locations with high concentration of concentric layers with progressively lower average intensity are considered suspicious deviations from normal parenchyma. The multiple concentric layers (MCLs) technique was trained and tested using the craniocaudal views of 270 mammographic cases with biopsy proven malignant masses from the digital database of screening mammography. One-half of the available cases were used for optimizing the parameters of the detection algorithm. The remaining cases were used for testing. During testing, malignant masses were detected with 92%, 88%, and 81% sensitivity at 5.4, 2.4, and 0.6 false positive marks per image. Testing on 82 normal screening mammograms showed a false positive rate of 5.0, 1.7, and 0.2 marks per image at the previously reported operating points. Furthermore, additional evaluation on 135 benign cases produced a significantly lower detection rate for benign masses (61.6%, 58.3%, and 43.7% at 5.1, 2.8, and 1.2 false positives per image, respectively). Overall, MCL is a promising computer-assisted detection strategy for screening mammograms to identify malignant masses while maintaining the detection rate of benign masses considerably lower.     

Motion-based object segmentation using hysteresis and bidirectional inter-frame change detection in sequences with moving camera

We present an unsupervised motion-based object segmentation algorithm for video sequences with moving camera, employing bidirectional inter-frame change detection. For every frame, two error frames are generated using motion compensation. They are combined and a segmentation algorithm based on thresholding is applied. We employ a simple and effective error fusion scheme and consider spatial error localization in the thresholding step. We find the optimal weights for the weighted mean thresholding algorithm that enables unsupervised robust moving object segmentation. Further, a post processing step for improving the temporal consistency of the segmentation masks is incorporated and thus we achieve improved performance compared to the previously proposed methods. The experimental evaluation and comparison with other methods demonstrate the validity of the proposed method.     

Discovery of [(2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl][5-methyl-2-(pyrimidin-2-yl)phenyl]methanone (MK-6096): a dual orexin receptor antagonist with potent sleep-promoting properties

Insomnia is a common disorder that can be comorbid with other physical and psychological illnesses. Traditional management of insomnia relies on general central nervous system (CNS) suppression using GABA modulators. Many of these agents fail to meet patient needs with respect to sleep onset, maintenance, and next-day residual effects and have issues related to tolerance, memory disturbances, and balance. Orexin neuropeptides are central regulators of wakefulness, and orexin antagonism has been identified as a novel mechanism for treating insomnia with clinical proof of concept. Herein we describe the discovery of a series of α-methylpiperidine carboxamide dual orexin?1 and orexin?2 receptor (OX(1) R/OX(2) R) antagonists (DORAs). The design of these molecules was inspired by earlier work from this laboratory in understanding preferred conformational properties for potent orexin receptor binding. Minimization of 1,3-allylic strain interactions was used as a design principle to synthesize 2,5-disubstituted piperidine carboxamides with axially oriented substituents including DORA 28. DORA 28 (MK-6096) has exceptional in?vivo activity in preclinical sleep models, and has advanced into phase?II clinical trials for the treatment of insomnia.     

Structure of a galactoarabinoglucuronoxylan from tamarillo (Solanum betaceum), a tropical exotic fruit,and its biological activity

Tamarillo (Solanum betaceum) is a tropical exotic fruit whose polysaccharides were extracted from the ripe pulp. After various purification steps, homogeneous fractions (designated PTW, STK-1000R and PF) were analyzed by sugar composition, HPSEC, methylation and NMR spectroscopy analysis. The results showed that the fraction PTW consisted of a linear arabinan with (1 → 5)-linked α-l-arabinofuranosyl units. Fractions designated as STK-1000R and PF contained galactoarabinoglucuronoxylans, with (1 → 4)-linked β-d-Xylp residues in the backbone, carrying branches exclusively at O-2. The polysaccharide in STK-1000R is less branched than that in the PF fraction (∼20.0% and 36.5%, respectively), with side-chains formed by (1 → 5)-linked α-l-Araf residues and (1 → 4)-linked α-d-GlcpA residues and with non-reducing end units formed by α-l-Araf, β-Arap, β-d-Galp, α-d-GlcpA and 4-O-Me-α-d-GlcpA. Intraperitoneal administration of the STK-1000R fraction in mice significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid and the inflammatory phase of nociception induced by 2.5% formalin, indicating that that fraction has an antinociceptive effect on inflammatory pain models.     

Activity of essential oil and its major compound, 1,8-cineole, from Eucalyptus globulus Labill., against the storage fungi Aspergillus flavus Link and Aspergillus parasiticus Speare

The essential oil from leaves of Eucalyptus globulus obtained by hydrodistillation, as well as its major compound 1,8-cineole, identified by gas chromatography coupled with a mass selective detector, were evaluated for their effectiveness against the storage fungi Aspergillus flavus and Aspergillus parasiticus. The evaluation was performed by compound dissolution in yeast extract sucrose (YES) medium and exposure to headspace volatiles. Complete fungal growth inhibition of both species was achieved with the essential oil by contact and volatile assays. Volatile exposure showed total inhibition at the lower level tested of 500 μL. The 1,8-cineole tested alone showed partial inhibition only at the highest level of 1.3492 μL. Aflatoxin B₁ production was reduced in headspace volatile assays and partial inhibition was observed at the 200 μL dose of the essential oil.     

Lactobacillus fermentum ACA-DC 179 displays probiotic potential in vitro and protects against trinitrobenzene sulfonic acid (TNBS)-induced colitis and Salmonella infection in murine models

Lactobacillus fermentum ACA-DC 179, Lactobacillus plantarum ACA-DC 287 and Streptococcus macedonicus ACA-DC 198 were studied for their probiotic potential. Firstly, strains were screened for antimicrobial activity towards a broad range of target strains, including lactic acid bacteria, food spoilage and pathogenic bacteria. L. fermentum ACA-DC 179 was active against five streptococci, including the two pathogenic strains Streptococcus oralis LMG 14532T and Streptococcus pneumoniae LMG 14545T. S. macedonicus ACA-DC 198 was active against the majority of the strains tested, including not only lactic acid bacteria but also many food spoilage or pathogenic species. The three potential probiotic strains were found to survive variably at pH 2.5 and were unaffected by bile salts. Only S. macedonicus ACA-DC 198 exhibited bile salt hydrolase activity, while none of the strains was haemolytic. Moreover, strains exhibited variable susceptibility towards commonly used antibiotics. L. plantarum ACA-DC 287 and S. macedonicus ACA-DC 198 induced the secretion of the pro-inflammatory cytokines IL-12, IFN-gamma and TNF-alpha by human peripheral blood mononuclear cells. Also elevated levels of the anti-inflammatory IL-10 were observed with L. fermentum ACA-DC 179. This strain consequently was found to significantly reduce colitis in a TNBS-induced colitis mouse model. Furthermore, L. fermentum ACA-DC 179 was successfully applied in an experimental Salmonella-infection mouse model. To conclude, strain L. fermentum ACA-DC 179 possesses desirable probiotic properties, such as antimicrobial activity and immunomodulation in vitro, which were confirmed in vivo by the use of animal models.     

Unveiling the Essential Role of Arkadia’s Non-RING Elements in the Ubiquitination Process

Arkadia is a positive regulator of the TGFβ-SMAD2/3 pathway, acting through its C-terminal RING-H2 domain and targeting for degradation of its negative regulators. Here we explore the role of regions outside the RING domain (non-RING elements) of Arkadia on the E2-E3 interaction. The contribution of the non-RING elements was addressed using Arkadia RING 68 aa and Arkadia 119 aa polypeptides. The highly conserved NRGA (asparagine-arginine-glycine-alanine) and TIER (threonine-isoleucine-glutamine-arginine) motifs within the 119 aa Arkadia polypeptide, have been shown to be required for pSMAD2/3 substrate recognition and ubiquitination in vivo. However, the role of the NRGA and TIER motifs in the enzymatic activity of Arkadia has not been addressed. Here, nuclear magnetic resonance interaction studies with the E2 enzyme, UBCH5B, C85S UBCH5B-Ub oxyester hydrolysis, and auto-ubiquitination assays were used to address the role of the non-RING elements in E2-E3 interaction and in the enzymatic activity of the RING. The results support that the non-RING elements including the NRGA and TIER motifs are required for E2-E3 recognition and interaction and for efficient auto-ubiquitination. Furthermore, while Arkadia isoform-2 and its close homologue Arkadia 2C are known to interact with free ubiquitin, the results here showed that Arkadia isoform-1 does not interact with free ubiquitin.     

Organizational socialization: Its content and consequences.

Content dimensions of the socialization domain were defined to determine relationships between learning particular features of a job/organization and the process and outcomes of socialization. Six socialization dimensions (performance proficiency, politics, language, people, organizational goals/values, and history) were supported by a factor analysis on data from 594 full-time professionals. The socialization process was then examined by comparing 3 groups of respondents who did not change jobs, changed jobs within the organization, or changed jobs and organizations. Results showed these groups had significantly different response patterns on all dimensions. Finally, relationships between socialization content and career outcomes showed the dimensions accounted for more variance in all criteria than typical tenure operationalizations of socialization. Furthermore, socialization changes were significantly related to changes in career outcomes for 1-, 2-, and 3-yr time intervals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)