Probabilistic segmentation of volume data for visualization using SOM-PNN classifier

We present a new probabilistic classifier, called SOM-PNN classifier, for volume data classification and visualization. The new classifier produces probabilistic classification with Bayesian confidence measure which is highly desirable in volume rendering. Based on the SOM map trained with a large training data set, our SOM-PNN classifier performs the probabilistic classification using the PNN algorithm. This combined use of SOM and PNN overcomes the shortcomings of the parametric methods, the nonparametric methods, and the SOM method. The proposed SOM-PNN classifier has been used to segment the CT sloth data and the 20 human MRI brain volumes resulting in much more informative 3D rendering with more details and less artifacts than other methods. Numerical comparisons demonstrate that the SOM-PNN classifier is a fast, accurate and probabilistic classifier for volume rendering.published_or_final_versio

Expanding the evolutionary explanations for sex differences in the human skeleton

While the anatomy and physiology of human reproduction differ between the sexes, the effects of hormones on skeletal growth do not. Human bone growth depends on estrogen. Greater estrogen produced by ovaries causes bones in female bodies to fuse before males\u27 resulting in sex differences in adult height and mass. Female pelves expand more than males\u27 due to estrogen and relaxin produced and employed by the tissues of the pelvic region and potentially also due to greater internal space occupied by female gonads and genitals. Evolutionary explanations for skeletal sex differences (aka sexual dimorphism) that focus too narrowly on big competitive men and broad birthing women must account for the adaptive biology of skeletal growth and its dependence on the developmental physiology of reproduction. In this case, dichotomizing evolution into proximate‐ultimate categories may be impeding the progress of human evolutionary science, as well as enabling the popular misunderstanding and abuse of it

Selective Targeting of Tumorigenic Cancer Cell Lines by Microtubule Inhibitors

For anticancer drug therapy, it is critical to kill those cells with highest tumorigenic potential, even when they comprise a relatively small fraction of the overall tumor cell population. We have used the established NCI/DTP 60 cell line growth inhibition assay as a platform for exploring the relationship between chemical structure and growth inhibition in both tumorigenic and non-tumorigenic cancer cell lines. Using experimental measurements of “take rate” in ectopic implants as a proxy for tumorigenic potential, we identified eight chemical agents that appear to strongly and selectively inhibit the growth of the most tumorigenic cell lines. Biochemical assay data and structure-activity relationships indicate that these compounds act by inhibiting tubulin polymerization. Yet, their activity against tumorigenic cell lines is more selective than that of the other microtubule inhibitors in clinical use. Biochemical differences in the tubulin subunits that make up microtubules, or differences in the function of microtubules in mitotic spindle assembly or cell division may be associated with the selectivity of these compounds

Fine mapping of genetic polymorphisms of pulmonary tuberculosis within chromosome 18q11.2 in the Chinese population: a case-control study

<p>Abstract</p> <p>Background</p> <p>Recently, one genome-wide association study identified a susceptibility locus of rs4331426 on chromosome 18q11.2 for tuberculosis in the African population. To validate the significance of this susceptibility locus in other areas, we conducted a case-control study in the Chinese population.</p> <p>Methods</p> <p>The present study consisted of 578 cases and 756 controls. The SNP rs4331426 and other six tag SNPs in the 100 Kbp up and down stream of rs4331426 on chromosome 18q11.2 were genotyped by using the Taqman-based allelic discrimination system.</p> <p>Results</p> <p>As compared with the findings from the African population, genetic variation of the SNP rs4331426 was rare among the Chinese. No significant differences were observed in genotypes or allele frequencies of the tag SNPs between cases and controls either before or after adjusting for age, sex, education, smoking, and drinking history. However, we observed strong linkage disequilibrium of SNPs. Constructed haplotypes within this block were linked the altered risks of tuberculosis. For example, in comparison with the common haplotype AA_{(rs8087945-rs12456774)}, haplotypes AG_{(rs8087945-rs12456774)}and GA_{(rs8087945-rs12456774)}were associated with a decreased risk of tuberculosis, with the adjusted odds ratio(95% confidence interval) of 0.34(0.27-0.42) and 0.22(0.16-0.29), respectively.</p> <p>Conclusions</p> <p>Susceptibility locus of rs4331426 discovered in the African population could not be validated in the Chinese population. None of genetic polymorphisms we genotyped were related to tuberculosis in the single-point analysis. However, haplotypes on chromosome 18q11.2 might contribute to an individual's susceptibility. More work is necessary to identify the true causative variants of tuberculosis.</p

Predicting Pneumonia and Influenza Mortality from Morbidity Data

BACKGROUND: Few European countries conduct reactive surveillance of influenza mortality, whereas most monitor morbidity. METHODOLOGY/PRINCIPAL FINDINGS: We developed a simple model based on Poisson seasonal regression to predict excess cases of pneumonia and influenza mortality during influenza epidemics, based on influenza morbidity data and the dominant types/subtypes of circulating viruses. Epidemics were classified in three levels of mortality burden (“high”, “moderate” and “low”). The model was fitted on 14 influenza seasons and was validated on six subsequent influenza seasons. Five out of the six seasons in the validation set were correctly classified. The average absolute difference between observed and predicted mortality was 2.8 per 100,000 (18% of the average excess mortality) and Spearman's rank correlation coefficient was 0.89 (P = 0.05). CONCLUSIONS/SIGNIFICANCE: The method described here can be used to estimate the influenza mortality burden in countries where specific pneumonia and influenza mortality surveillance data are not available

The incidence of liver injury in Uyghur patients treated for TB in Xinjiang Uyghur autonomous region, China, and its association with hepatic enzyme polymorphisms nat2, cyp2e1, gstm1 and gstt1.

BACKGROUND AND OBJECTIVE: Of three first-line anti-tuberculosis (anti-TB) drugs, isoniazid is most commonly associated with hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, NAT2, CYP2E1, GSTM1and GSTT1, that code for drug-metabolizing enzymes. This study evaluated whether the polymorphisms in these enzymes were associated with an increased risk of anti-TB drug-induced hepatitis in patients and could potentially be used to identify patients at risk of liver injury. METHODS AND DESIGN: In a cross-sectional study, 2244 tuberculosis patients were assessed two months after the start of treatment. Anti-TB drug-induced liver injury (ATLI) was defined as an ALT, AST or bilirubin value more than twice the upper limit of normal. NAT2, CYP2E1, GSTM1 and GSTT1 genotypes were determined using the PCR/ligase detection reaction assays. RESULTS: 2244 patients were evaluated, there were 89 cases of ATLI, a prevalence of 4% 9 patients (0.4%) had ALT levels more than 5 times the upper limit of normal. The prevalence of ATLI was greater among men than women, and there was a weak association with NAT2*5 genotypes, with ATLI more common among patients with the NAT2*5*CT genotype. The sensitivity of the CT genotype for identifying patients with ATLI was 42% and the positive predictive value 5.9%. CT ATLI was more common among slow acetylators (prevalence ratio 2.0 (95% CI 0.95,4.20) )compared to rapid acetylators. There was no evidence that ATLI was associated with CYP2E1 RsaIc1/c1genotype, CYP2E1 RsaIc1/c2 or c2/c2 genotypes, or GSTM1/GSTT1 null genotypes. CONCLUSIONS: In Xinjiang Uyghur TB patients, liver injury was associated with the genetic variant NAT2*5, however the genetic markers studied are unlikely to be useful for screening patients due to the low sensitivity and low positive predictive values for identifying persons at risk of liver injury

Rapid Analysis of Listeria monocytogenes Cell Wall Teichoic Acid Carbohydrates by ESI-MS/MS

We report the application of electrospray ionization (ESI) mass spectrometry for compositional characterization of wall teichoic acids (WTA), a major component of Gram-positive bacterial cell walls. Tandem mass spectrometry (ESI-MS/MS) of purified and chemically hydrolyzed monomeric WTA components provided sufficient information to identify WTA monomers and their specific carbohydrate constituents. A lithium matrix was used for ionization of uncharged WTA monomers, and successfully applied to analyze the WTA molecules of four Listeria strains differing in carbohydrate substitution on a conserved polyribitol-phosphate backbone structure. Carbohydrate residues such as N-acetylglucosamine or rhamnose linked to the WTA could directly be identified by ESI-MS/MS, circumventing the need for quantitative analysis by gas chromatography. The presence of a terminal N-acetylglucosamine residue tethered to the ribitol was confirmed using fluorescently labeled wheat-germ agglutinin. In conclusion, the mass spectrometry method described here will greatly facilitate compositional analysis and characterization of teichoic acids and similar macromolecules from diverse bacterial species, and represents a significant advance in the identification of serovar-specific carbohydrates and sugar molecules on bacteria

Selective Synthesis of Fe2O3 and Fe3O4 Nanowires Via a Single Precursor: A General Method for Metal Oxide Nanowires

Hematite (α-Fe2O3) and magnetite (Fe3O4) nanowires with the diameter of about 100 nm and the length of tens of micrometers have been selectively synthesized by a microemulsion-based method in combination of the calcinations under different atmosphere. The effects of the precursors, annealing temperature, and atmosphere on the morphology and the structure of the products have been investigated. Moreover, Co3O4 nanowires have been fabricated to confirm the versatility of the method for metal oxide nanowires

Efficient Allele-Specific Targeting of LRRK2 R1441 Mutations Mediated by RNAi

Since RNA interference (RNAi) has the potential to discriminate between single nucleotide changes, there is growing interest in the use of RNAi as a promising therapeutical approach to target dominant disease-associated alleles. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been linked to dominantly inherited Parkinson's disease (PD). We focused on three LRRK2 mutations (R1441G/C and the more prevalent G2109S) hoping to identify shRNAs that would both recognize and efficiently silence the mutated alleles preferentially over the wild-type alleles. Using a luciferase-based reporter system, we identified shRNAs that were able to specifically target the R1441G and R1441C alleles with 80% silencing efficiency. The same shRNAs were able to silence specifically mRNAs encoding either partial or full-length mutant LRRK2 fusion proteins, while having a minimal effect on endogenous wild-type LRRK2 expression when transfected in 293FT cells. Shifting of the mutant recognition site (MRS) from position 11 to other sites (4 and 16, within the 19-mer window of our shRNA design) reduced specificity and overall silencing efficiency. Developing an allele-specific RNAi of G2019S was problematic. Placement of the MRS at position 10 resulted in efficient silencing of reporters (75–80%), but failed to discriminate between mutant and wild-type alleles. Shifting of the MRS to positions 4, 5, 15, 16 increased the specificity of the shRNAs, but reduced the overall silencing efficiency. Consistent with previous reports, these data confirm that MRS placement influences both allele-specificity and silencing strength of shRNAs, while further modification to hairpin design or MRS position may lead to the development of effective G2019S shRNAs. In summary, the effective shRNA against LRRK2 R1441 alleles described herein suggests that RNAi-based therapy of inherited Parkinson's disease is a viable approach towards developing effective therapeutic interventions for this serious neurodegenerative disease

Transgenic Rat Model of Neurodegeneration Caused by Mutation in the TDP Gene

TDP-43 proteinopathies have been observed in a wide range of neurodegenerative diseases. Mutations in the gene encoding TDP-43 (i.e., TDP) have been identified in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobe degeneration associated with motor neuron disease. To study the consequences of TDP mutation in an intact system, we created transgenic rats expressing normal human TDP or a mutant form of human TDP with a M337V substitution. Overexpression of mutant, but not normal, TDP caused widespread neurodegeneration that predominantly affected the motor system. TDP mutation reproduced ALS phenotypes in transgenic rats, as seen by progressive degeneration of motor neurons and denervation atrophy of skeletal muscles. This robust rat model also recapitulated features of TDP-43 proteinopathies including the formation of TDP-43 inclusions, cytoplasmic localization of phosphorylated TDP-43, and fragmentation of TDP-43 protein. TDP transgenic rats will be useful for deciphering the mechanisms underlying TDP-43–related neurodegenerative diseases