Using DFB laser self-injection locked to an optical waveguide ring resonator as a light source of Φ-OTDR.

A distributed feedback (DFB) semiconductor laser self-injection locked to an optical waveguide ring resonator (OWRR) is used in a phase-sensitive optical time-domain reflectometry (Φ-OTDR) vibration sensing system as its light source. A frequency-hopping-free period of more than 100 s is realized. A spatial resolution of 13 m at 4700 m and simultaneous measurement of two vibration sources are realized. The measurable vibration frequency is from 8 Hz to the upper limit of the sampling theorem. These satisfactory performances demonstrate that the DFB laser locked to an OWRR is not only cost effective, but also stable and reliable for Φ-OTDR sensing.

The ratio of the maximum density values: a new method for predicting hemorrhagic transformation in acute ischemic stroke patients undergoing mechanical thrombectomy.

Background: It is challenging yet critical to differentiate between hemorrhagic transformation (HT) and contrast extravasation on non-contrast-enhanced computed tomography (NCCT) scans following mechanical thrombectomy (MT) in patients with acute ischemic stroke. We propose a new method called the ratio of maximum density values (RMDV) to minimize the confusion of contrast extravasation and to evaluate the diagnostic significance of RMDV in predicting HT on immediate post-interventional NCCT scans. Methods: We conducted a retrospective analysis of the prospective patients' database who received MT for acute ischemic stroke caused by occlusion of the intracranial large artery and showed postinterventional cerebral hyperdensities (PCHDs) on NCCT scans immediately after MT. Based on the subsequent NCCT scans, we divided patients with PCHDs into the HT and the non-HT groups. The clinical characters and radiological details were collected and compared to the two groups. We assessed the ability of RMDV >1 to predict HT by analyzing the receiver operating characteristic curve. Results: One hundred and three patients showed PCHDs; 58 (56.31%) were classified as HT, while 45 (43.69%) were classified as non-HT. The only notable distinction between the two groups was the proportion of RMDV >1 in the HT group. The correlation between HT and RMDV >1 with an area under the curve of 0.826 (95% confidence interval, 0.739 to 0.894). The sensitivity, specificity, positive, and negative predictive values of RMDV >1 on NCCT for predicting HT were 89.66, 75.56, 82.54, and 85.00%, respectively. Conclusion: The utilization of RMDV >1 on immediate NCCT scans after MT can predict early HT with good sensitivity and specificity.

A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes.

Immune reconstitution has improved outcomes for progressive multifocal leukoencephalopathy (PML), a potentially lethal brain disease caused by JC virus (JCV). However, an antiviral treatment to control JCV is needed when immune reconstitution is delayed or not possible. On the basis of in vitro efficacy, this study evaluated the effect of mefloquine on PML and factors that may predict PML outcomes. This 38-week, open-label, randomized, parallel-group, proof-of-concept study compared patients with PML who received standard of care (SOC) with those who received SOC plus mefloquine (250 mg for 3 days, then 250 mg weekly). Patients randomized to SOC could add mefloquine treatment at week 4. The primary endpoint was change from baseline to weeks 4 and 8 in JCV DNA copy number (load) in cerebrospinal fluid (CSF). Exploratory analyses evaluated factors that might correlate with clinical outcome. The majority of enrolled patients were HIV positive. Preplanned interim data analyses suggested that the study was unlikely to successfully demonstrate a significant difference between groups; therefore, the study was terminated prematurely. There was no significant difference between groups in CSF JCV DNA loads or clinical/MRI findings. Decrease in CSF JCV DNA load from baseline to week 4 was associated with a better clinical outcome at 16 weeks, as measured by Karnofsky scores. This study found no evidence of anti-JCV activity by mefloquine. An early decrease of CSF JCV DNA load appears to be associated with a better clinical outcome.

[The LIBS experiment condition optimization of alloy steel].

Laser induced plasma spectroscopy of alloy steel was produced by Nd : YAG pulsed laser at 1 064 nm, and the spectral signal was detected by high resolution and width controlled ICCD. Several Fe atomic spectral lines such as 404.581, 414.387, 427.176 and 438.355 nm were chosen for analysis, and the effects of different experimental parameters on LIBS spectral signal intensity were investigated. It is shown that the experimental parameters such as pulse energy, laser focus location and laser delay time have great influence on the LIBS signal. LIBS signals with high spectral intensity and signal-background ratio (SBR) as well as the optimum experiment conditions were obtained by optimizing these experiment parameters so as to make composition analysis of the alloy steel.

Characteristics and mechanisms of large-scale old landslides and landslide dams in the Loess Plateau-A case study from Daning County, Shanxi Province, China.

Giant landslides and dammed lakes occurred frequently during the prehistoric period; however, their mechanisms often remain an open issue because they are complex. This study used field investigations to observe four old landslides and three landslide dams in Daning County, Shanxi Province, China. Remote sensing images captured during different periods were used to compare the landforms of landslides, landslide dams, and their surrounding environments in detail. Subsequently, their shapes, scales, spatial distributions, and positional relationships were determined. The ages of 14C obtained from the paleolandslide dam lake (PDL) deposits were 3742 ± 95, 4115 ± 121, 6544 ± 91, 7814 ± 109 cal a BP. The 14C ages of the deposits under the sliding surfaces of the old landslides were 2748 ± 27, 4470 ± 54, and 8245 ± 79 cal a BP. Based on the actual physical geographical conditions and geomorphological characteristics of the region, combined with the above age data, that the following conclusions were made: (i) During the Holocene, from 2700 to 8200 years ago, heavy rainfall was the main reason for the occurrence of landslides and landslide dams in the region. (ii) Under the condition of heavy rainfall, the slopes with angles >60° in the Loess Plateau are prone to form landslide masses, and the size of the landslide is related to rainfall intensity. A landslide dam was easily formed when the sliding direction was perpendicular to the direction of the valley. It is difficult to form landslide dams when the sliding direction is almost consistent with the downward direction of the valley. (iii) The formation mechanism of old landslides shows that collapse or sliding may occur suddenly in loess geological masses under an external rainfall scenario. Moreover, the process of landslide dams is related to the geomorphic forms of the original valley.

Triggering and guiding high-voltage discharge in air by single and multiple femtosecond filaments.

The abilities to trigger and guide high-voltage discharge by using single and multiple filaments (MFs) are experimentally studied. It is shown that the discharge voltage threshold can be reduced significantly in both regimes of single and MF; however, the MF does not gain a larger reduction than a single filament. This behavior of the MF is attributed to the single discharge path rather than simultaneous multiple ones as one might expect during the discharge process.

The coexistence of a patent foramen ovale and obstructive sleep apnea may increase the risk of wake-up stroke in young adults.

BACKGROUND: Patent foramen ovale (PFO) and obstructive sleep apnea (OSA) are independent risk factors for young conscious stroke which may also be concomitant symptoms with it. But there is no sufficient attention on these phenomena. OBJECTIVE: To investigate the relationship between PFO, OSA and young stroke, and to look for proper treatment. METHODS: Three patients with young conscious stroke were reported, each of them was combined with PFO and OSA. All patients were diagnosed as wake-up stroke (WUS). Contrast-enhanced transcranial doppler ultrasound (c-TCD) and polysomnography (PSG) test were used for auxiliary diagnosis. RESULTS: Right-to-left shunts and moderate to severe sleep apnea were observed. Increased body mass index (BMI), hemoglobin (HGB) and hematocrit (HCT) index were also observed. After continuous positive airway pressure (CPAP) therapy, the number of microbubbles was reduced in one patient. CONCLUSIONS: These suggest that coexistence of PFO and OSA may associate with a greater risk of youth stroke. Decrease risk of stroke might occur if treating with CPAP in patients with OSA.

Imputation of missing genotypes: an empirical evaluation of IMPUTE.

BACKGROUND: Imputation of missing genotypes is becoming a very popular solution for synchronizing genotype data collected with different microarray platforms but the effect of ethnic background, subject ascertainment, and amount of missing data on the accuracy of imputation are not well understood. RESULTS: We evaluated the accuracy of the program IMPUTE to generate the genotype data of partially or fully untyped single nucleotide polymorphisms (SNPs). The program uses a model-based approach to imputation that reconstructs the genotype distribution given a set of referent haplotypes and the observed data, and uses this distribution to compute the marginal probability of each missing genotype for each individual subject that is used to impute the missing data. We assembled genome-wide data from five different studies and three different ethnic groups comprising Caucasians, African Americans and Asians. We randomly removed genotype data and then compared the observed genotypes with those generated by IMPUTE. Our analysis shows 97% median accuracy in Caucasian subjects when less than 10% of the SNPs are untyped and missing genotypes are accepted regardless of their posterior probability. The median accuracy increases to 99% when we require 0.95 minimum posterior probability for an imputed genotype to be acceptable. The accuracy decreases to 86% or 94% when subjects are African Americans or Asians. We propose a strategy to improve the accuracy by leveraging the level of admixture in African Americans. CONCLUSION: Our analysis suggests that IMPUTE is very accurate in samples of Caucasians origin, it is slightly less accurate in samples of Asians background, but substantially less accurate in samples of admixed background such as African Americans. Sample size and ascertainment do not seem to affect the accuracy of imputation.

A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples.

BACKGROUND: One of the challenges of the analysis of pooling-based genome wide association studies is to identify authentic associations among potentially thousands of false positive associations. RESULTS: We present a hierarchical and modular approach to the analysis of genome wide genotype data that incorporates quality control, linkage disequilibrium, physical distance and gene ontology to identify authentic associations among those found by statistical association tests. The method is developed for the allelic association analysis of pooled DNA samples, but it can be easily generalized to the analysis of individually genotyped samples. We evaluate the approach using data sets from diverse genome wide association studies including fetal hemoglobin levels in sickle cell anemia and a sample of centenarians and show that the approach is highly reproducible and allows for discovery at different levels of synthesis. CONCLUSION: Results from the integration of Bayesian tests and other machine learning techniques with linkage disequilibrium data suggest that we do not need to use too stringent thresholds to reduce the number of false positive associations. This method yields increased power even with relatively small samples. In fact, our evaluation shows that the method can reach almost 70% sensitivity with samples of only 100 subjects.

Microwave guiding along double femtosecond filaments in air.

Microwave guiding along double parallel lines of femtosecond-laser-generated plasma filament has been demonstrated over a distance of about 8 cm in air, corresponding to a maximum microwave signal intensity enhancement more than sixfold the free-space propagation. It is shown that the operating frequency and the line electric width influence the propagation coefficient of microwaves propagating along this transmission line. Based on channeling microwaves along this line and by measuring and comparing the propagated microwave signals, the basic parameters of laser-generated plasma filament, namely, its electron density and conductivity, are obtained.

Comparison of disease activity in SPMS and PPMS in the context of multicenter clinical trials.

BACKGROUND: Retrospective single center natural history studies have shown that times to reach disability milestones and ages at which they are reached are similar in primary (PPMS) and secondary (SPMS) progressive multiple sclerosis suggesting that they may be phenotypic variations of the same disease. OBJECTIVE: Here we compared longitudinal disease activity in SPMS and PPMS in the context of international multicenter clinical trials. METHODS: We analyzed all objective outcome measures that were systematically collected over 2 years for all subjects randomized to placebo arms in one SPMS and one PPMS clinical trial over the last decade. Conventional and exploratory definitions of clinical disease activity were used. Disease activity was analyzed in 3 different categories intermittent activity, progression, and improvement. Conventional MRI measures and one patient reported outcome measure of quality of life were included when available for comparison. Heat maps were drawn for all results followed by hierarchical clustering. RESULTS: There were 101 outcome variables from 206 SPMS subjects and 79 outcome variables from 135 PPMS subjects. The comparison revealed that SPMS and PPMS subjects exhibited similar disease activity over 2 years in all but two of the variables in common worsening in the EDSS sensory system was more common in PPMS while worsening on the 9 hole PEG was more common in SPMS. Intermittent activity was the most common pattern of disease activity in SPMS and PPMS. Clinical worsening and improvement occurred at similar frequency in both. CONCLUSION: Longitudinal disease activity was nearly identical in SPMS and PPMS subjects in the context of the two multicenter international clinical trials we examined.

Autoantigen discovery with a synthetic human peptidome.

Immune responses targeting self-proteins (autoantigens) can lead to a variety of autoimmune diseases. Identification of these antigens is important for both diagnostic and therapeutic reasons. However, current approaches to characterize autoantigens have, in most cases, met only with limited success. Here we present a synthetic representation of the complete human proteome, the T7 peptidome phage display library (T7-Pep), and demonstrate its application to autoantigen discovery. T7-Pep is composed of >413,000 36-residue, overlapping peptides that cover all open reading frames in the human genome, and can be analyzed using high-throughput DNA sequencing. We developed a phage immunoprecipitation sequencing (PhIP-Seq) methodology to identify known and previously unreported autoantibodies contained in the spinal fluid of three individuals with paraneoplastic neurological syndromes. We also show how T7-Pep can be used more generally to identify peptide-protein interactions, suggesting the broader utility of our approach for proteomic research.

The relation of genetic and environmental factors to systemic inflammatory biomarker concentrations.

BACKGROUND: Environmental and genetic correlates of inflammatory marker variability are incompletely understood. In the family-based Framingham Heart Study, we investigated heritability and candidate gene associations of systemic inflammatory biomarkers. METHODS AND RESULTS: In offspring participants (n=3710), we examined 11 inflammatory biomarkers (CD40 ligand, C-reactive protein, intercellular adhesion molecule-1, interleukin-6, urinary isoprostanes, monocyte chemoattractant protein-1, myeloperoxidase, P-selectin, tumor necrosis factor-alpha, tumor necrosis factor receptor II, fibrinogen). Heritability and bivariate genetic and environmental correlations were assessed by Sequential Oligogenic Linkage Analysis routines in 1012 family members. We examined 1943 tagging single-nucleotide polymorphisms in 233 inflammatory pathway genes with >or=5 minor allele carriers using a general genetic linear model. Clinical correlates explained 2.4% (CD40 ligand) to 28.5% (C-reactive protein) of the variability in inflammatory biomarkers. Estimated heritability ranged from 10.9% (isoprostanes) to 44.8% (P-selectin). Most correlations between biomarkers were weak although statistically significant. A total of 45 single-nucleotide polymorphism-biomarker associations met the q-value threshold of 0.25. Novel top single-nucleotide polymorphisms were observed in ICAM1 gene in relation to intercellular adhesion molecule-1 concentrations (rs1799969, P=1.32 x 10(-8)) and MPO in relation to myeloperoxidase (rs28730837, P=1.9 x 10(-5)). Lowest P values for trans-acting single-nucleotide polymorphisms were observed for APCS with monocyte chemoattractant protein-1 concentrations (rs1374486, P=1.01 x 10(-7)) and confirmed for IL6R with interleukin-6 concentrations (rs8192284, P=3.36 x 10(-5)). Novel potential candidates (APCS, MPO) need to be replicated. CONCLUSIONS: Our community-based data support the relevance of clinical and genetic factors for explaining variation in inflammatory biomarker traits.

Global protein stability profiling in mammalian cells.

The abundance of cellular proteins is determined largely by the rate of transcription and translation coupled with the stability of individual proteins. Although we know a great deal about global transcript abundance, little is known about global protein stability. We present a highly parallel multiplexing strategy to monitor protein turnover on a global scale by coupling flow cytometry with microarray technology to track the stability of individual proteins within a complex mixture. We demonstrated the feasibility of this approach by measuring the stability of approximately 8000 human proteins and identifying proteasome substrates. The technology provides a general platform for proteome-scale analysis of protein turnover under various physiological and disease conditions.

Cancer proliferation gene discovery through functional genomics.

Retroviral short hairpin RNA (shRNA)-mediated genetic screens in mammalian cells are powerful tools for discovering loss-of-function phenotypes. We describe a highly parallel multiplex methodology for screening large pools of shRNAs using half-hairpin barcodes for microarray deconvolution. We carried out dropout screens for shRNAs that affect cell proliferation and viability in cancer cells and normal cells. We identified many shRNAs to be antiproliferative that target core cellular processes, such as the cell cycle and protein translation, in all cells examined. Moreover, we identified genes that are selectively required for proliferation and survival in different cell lines. Our platform enables rapid and cost-effective genome-wide screens to identify cancer proliferation and survival genes for target discovery. Such efforts are complementary to the Cancer Genome Atlas and provide an alternative functional view of cancer cells.

ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

Cellular responses to DNA damage are mediated by a number of protein kinases, including ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related). The outlines of the signal transduction portion of this pathway are known, but little is known about the physiological scope of the DNA damage response (DDR). We performed a large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR and identified more than 900 regulated phosphorylation sites encompassing over 700 proteins. Functional analysis of a subset of this data set indicated that this list is highly enriched for proteins involved in the DDR. This set of proteins is highly interconnected, and we identified a large number of protein modules and networks not previously linked to the DDR. This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals.

Data mining, neural nets, trees--problems 2 and 3 of Genetic Analysis Workshop 15.

Genome-wide association studies using thousands to hundreds of thousands of single nucleotide polymorphism (SNP) markers and region-wide association studies using a dense panel of SNPs are already in use to identify disease susceptibility genes and to predict disease risk in individuals. Because these tasks become increasingly important, three different data sets were provided for the Genetic Analysis Workshop 15, thus allowing examination of various novel and existing data mining methods for both classification and identification of disease susceptibility genes, gene by gene or gene by environment interaction. The approach most often applied in this presentation group was random forests because of its simplicity, elegance, and robustness. It was used for prediction and for screening for interesting SNPs in a first step. The logistic tree with unbiased selection approach appeared to be an interesting alternative to efficiently select interesting SNPs. Machine learning, specifically ensemble methods, might be useful as pre-screening tools for large-scale association studies because they can be less prone to overfitting, can be less computer processor time intensive, can easily include pair-wise and higher-order interactions compared with standard statistical approaches and can also have a high capability for classification. However, improved implementations that are able to deal with hundreds of thousands of SNPs at a time are required.

A novel cytology-based, two-hybrid screen for bacteria applied to protein-protein interaction studies of a type IV secretion system.

DivIVA of Bacillus subtilis and FtsZ of Escherichia coli were used to target heterologous protein complexes to cell division sites of E. coli and Agrobacterium tumefaciens. DivIVA and FtsZ that were fused to the dimerizing leucine zipper (LZ) domain of the yeast transcription activator GCN4 directed the green fluorescent protein (GFP) that was fused to an LZ domain to E. coli division sites, resulting in fluorescence patterns identical to those observed with DivIVA::GFP and FtsZ::GFP. These cell division proteins also targeted the VirE1 chaperone and VirE2 secretion substrate complex to division sites of E. coli and A. tumefaciens. Coproduction of the native VirE1 or VirE2 proteins inhibited the dihybrid interaction in both species, as judged by loss of GFP targeting to division sites. The VirE1 chaperone bound independently to N- and C-terminal regions of VirE2, with a requirement for residues 84 to 147 and 331 to 405 for these interactions, as shown by dihybrid studies with VirE1::GFP and DivIVA fused to N- and C-terminal VirE2 fragments. DivIVA also targeted homo- and heterotypic complexes of VirB8 and VirB10, two bitopic inner membrane subunits of the A. tumefaciens T-DNA transfer system, in E. coli and homotypic complexes of VirB10 in A. tumefaciens. VirB10 self-association in bacteria was mediated by the C-terminal periplasmic domain, as shown by dihybrid studies with fusions to VirB10 truncation derivatives. Together, our findings establish a proof-of-concept for the use of cell-location-specific proteins for studies of interactions among cytosolic and membrane proteins in diverse bacterial species.

[Clinical study of the hemodynamics of both ends (proximal and distal) of internal mammary artery and its following-up].

OBJECTIVE: To verify the value of retrograde flow of Internal Mammary Artery (IMA) used as one of the supplying arteries and to develop a new method of applying IMA in breast reconstruction. METHODS: During breast reconstruction with free bilateral transverse rectus abdominis myocutaneous (TRAM) flap, the pressures and velocities of the two ends (proximal and distal) of internal mammary artery as well as the according perfusion unit (PU) of TRAM were measured in two patients who suffered from mammectomy because of carcinoma. RESULTS: The pressure at distal end was 66 or/and 58 mmHg, the pressure at proximal end was 88 or/and 75 mmHg, the former is 75%-77% of the later. The immediate rate of blood flow of distal anastomotic stoma was 74 or/and 52 ml/min, that of proximal was 94 or/and 70 ml/min, the former is 74%-78% of the later after anastomosed to the two sides of deep inferior epigastric arteries (DIEA) separately. Under condition that both ends (proximal and distal) of IMA contributing as the supplying blood vessels simultaneously, the PU of TRAM was the best. The rates of blood flow at the two anastomotic stomas are similar to each other in late stage (evaluated at the fifth year follow-up). CONCLUSION: The distal end of internal mammary artery can supply blood flow in a considerable level, similar with the proximal end.