Optical attenuation mechanism upgrades, MOBLAS, and TLRS systems

This poster presentation describes the Optical Attenuation Mechanism (OAM) Upgrades to the MOBLAS and TLRS Crustal Dynamics Satellite Laser Ranging (CDSLR) systems. The upgrades were for the purposes of preparing these systems to laser range to the TOPEX/POSEIDON spacecraft when it will be launched in the summer of 1992. The OAM permits the laser receiver to operate over the expected large signal dynamic range from TOPEX/POSEIDON and it reduces the number of pre- and post-calibrations for each satellite during multi-satellite tracking operations. It further simplifies the calibration bias corrections that had been made due to the pass-to-pass variation of the photomultiplier supply voltage and the transmit filter glass thickness. The upgrade incorporated improvements to the optical alignment capability of each CDSLR system through the addition of a CCD camera into the MOBLAS receive telescope and an alignment telescope onto the TLRS optical table. The OAM is stepper motor and microprocessor based; and the system can be controlled either manually by a control switch panel or computer controlled via an EIA RS-232C serial interface. The OAM has a neutral density (ND) range of 0.0 to 4.0 and the positioning is absolute referenced in steps of 0.1 ND. Both the fixed transmit filter and the daylight filter are solenoid actuated with digital inputs and outputs to and from the OAM microprocessor. During automated operation, the operator has the option to overide the remote control and control the OAM system via a local control switch panel

Network analysis of genes regulated in renal diseases: implications for a molecular-based classification

Abstract Background Chronic renal diseases are currently classified based on morphological similarities such as whether they produce predominantly inflammatory or non-inflammatory responses. However, such classifications do not reliably predict the course of the disease and its response to therapy. In contrast, recent studies in diseases such as breast cancer suggest that a classification which includes molecular information could lead to more accurate diagnoses and prediction of treatment response. This article describes how we extracted gene expression profiles from biopsies of patients with chronic renal diseases, and used network visualizations and associated quantitative measures to rapidly analyze similarities and differences between the diseases. Results The analysis revealed three main regularities: (1) Many genes associated with a single disease, and fewer genes associated with many diseases. (2) Unexpected combinations of renal diseases that share relatively large numbers of genes. (3) Uniform concordance in the regulation of all genes in the network. Conclusion The overall results suggest the need to define a molecular-based classification of renal diseases, in addition to hypotheses for the unexpected patterns of shared genes and the uniformity in gene concordance. Furthermore, the results demonstrate the utility of network analyses to rapidly understand complex relationships between diseases and regulated genes.http://deepblue.lib.umich.edu/bitstream/2027.42/112463/1/12859_2009_Article_3354.pd

Superficial thrombophlebitis and risk for recurrent venous thromboembolism

AbstractObjective: Superficial thrombophlebitis (ST) is a frequent and potentially serious disease if complicated with venous thromboembolism (VTE). Data on risk factors and incidence rates for ST are scarce. It is also unknown whether ST is a risk factor for recurrence of VTE. Methods: After discontinuation of secondary thromboprophylaxis for a first spontaneous VTE, we prospectively observed 615 patients on average for 30 ± 26 months. Patients with natural coagulation inhibitor deficiency, lupus anticoagulant, or cancer, who were pregnant, or were receiving long-term antithrombotic therapy were excluded. The study outcomes were occurrence of symptomatic ST or objectively documented recurrent symptomatic VTE. Results: ST developed in 45 patients (7.3%) with a first VTE. High factor VIII concentration emerged as an independent risk factor for ST (relative risk [RR], 2.0; 95% confidence interval [CI], 1.0-5.2), compared with lower levels after adjustment for age and sex; factor V Leiden and prothrombin G20210A concentration; hyperhomocysteinemia; high body mass index; and duration of oral anticoagulation therapy. VTE recurred in 12 (27%) of 45 patients with ST and in 67 (12%) of 570 patients without ST. In patients with VTE, subsequent ST emerged as an independent risk factor for recurrent VTE. Patients with ST had twofold higher RR (2.1; 95% CI, 1.0-4.2) for recurrence than did patients without ST after adjustment for putative confounding variables. Conclusion: Patients with a first spontaneous VTE and subsequent ST are at increased risk for recurrent VTE. High factor VIII concentration is an independent risk factor for ST. (J Vasc Surg 2003;37:834-8.

The Dictyostelium genome encodes numerous RasGEFs with multiple biological roles

BACKGROUND: Dictyostelium discoideum is a eukaryote with a simple lifestyle and a relatively small genome whose sequence has been fully determined. It is widely used for studies on cell signaling, movement and multicellular development. Ras guanine-nucleotide exchange factors (RasGEFs) are the proteins that activate Ras and thus lie near the top of many signaling pathways. They are particularly important for signaling in development and chemotaxis in many organisms, including Dictyostelium. RESULTS: We have searched the genome for sequences encoding RasGEFs. Despite its relative simplicity, we find that the Dictyostelium genome encodes at least 25 RasGEFs, with a few other genes encoding only parts of the RasGEF consensus domains. All appear to be expressed at some point in development. The 25 genes include a wide variety of domain structures, most of which have not been seen in other organisms. The LisH domain, which is associated with microtubule binding, is seen particularly frequently; other domains that confer interactions with the cytoskeleton are also common. Disruption of a sample of the novel genes reveals that many have clear phenotypes, including altered morphology and defects in chemotaxis, slug phototaxis and thermotaxis. CONCLUSION: These results suggest that the unexpectedly large number of RasGEF genes reflects an evolutionary expansion of the range of Ras signaling rather than functional redundancy or the presence of multiple pseudogenes

AI-based detection of contrast-enhancing MRI lesions in patients with multiple sclerosis.

BACKGROUND Contrast-enhancing (CE) lesions are an important finding on brain magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) but can be missed easily. Automated solutions for reliable CE lesion detection are emerging; however, independent validation of artificial intelligence (AI) tools in the clinical routine is still rare. METHODS A three-dimensional convolutional neural network for CE lesion segmentation was trained externally on 1488 datasets of 934 MS patients from 81 scanners using concatenated information from FLAIR and T1-weighted post-contrast imaging. This externally trained model was tested on an independent dataset comprising 504 T1-weighted post-contrast and FLAIR image datasets of MS patients from clinical routine. Two neuroradiologists (R1, R2) labeled CE lesions for gold standard definition in the clinical test dataset. The algorithmic output was evaluated on both patient- and lesion-level. RESULTS On a patient-level, recall, specificity, precision, and accuracy of the AI tool to predict patients with CE lesions were 0.75, 0.99, 0.91, and 0.96. The agreement between the AI tool and both readers was within the range of inter-rater agreement (Cohen's kappa; AI vs. R1: 0.69; AI vs. R2: 0.76; R1 vs. R2: 0.76). On a lesion-level, false negative lesions were predominately found in infratentorial location, significantly smaller, and at lower contrast than true positive lesions (p < 0.05). CONCLUSIONS AI-based identification of CE lesions on brain MRI is feasible, approaching human reader performance in independent clinical data and might be of help as a second reader in the neuroradiological assessment of active inflammation in MS patients. CRITICAL RELEVANCE STATEMENT Al-based detection of contrast-enhancing multiple sclerosis lesions approaches human reader performance, but careful visual inspection is still needed, especially for infratentorial, small and low-contrast lesions

Hematocrit and the Risk of Recurrent Venous Thrombosis: A Prospective Cohort Study

BACKGROUND: Venous thromboembolism (VTE) is a multicausal disease which recurs. Hematocrit is associated with a thrombotic risk. We aimed to investigate if hematocrit is associated with the recurrence risk. METHODS: Patients with a first VTE were followed after anticoagulation. Patients with VTE provoked by a transient risk factor, natural inhibitor deficiency, lupus anticoagulant, homozygous or double heterozygous defects, cancer, or long-term antithrombotic treatment were excluded. The study endpoint was recurrent VTE. RESULTS: 150 (23%) of 653 patients had recurrence. Only high hematocrit was significantly associated with recurrence risk [hazard ratio (HR) for 1% hematocrit increase with the third tertile 1.08; 95% CI 1.01-1.15]. No or only a weak association for hematocrits within the first and second tertile was seen (HR 1.03; 95% CI 0.97-1.09, and 1.07; 95% CI 1.00-1.13). Hematocrit was associated with recurrence risk only among women. After five years, the probability of recurrence was 9.9% (95% CI 3.7%-15.7%), 15.6% (95% CI 9.7%-21.2%) and 25.5% (95% CI 15.1%-34.6%) in women, and was 29.2% (95% CI 21.1%-36.5%), 30.1% (95% CI 24.1%-35.7%) and 30.8% (95% CI 22.0%-38.7%) in men for hematocrits in the first, second and third tertile, respectively. Men had a higher recurrence risk (1.9; 95% CI 1.1-2.7; p = 0.03), which dropped by 23.5% after adjustment for hematocrit. Hematocrit was not a significant mediator of the sex-difference in recurrence risk (p = 0.223). CONCLUSIONS: High hematocrit is associated with the recurrence only in women. The different recurrence risk between men and women is possibly partly explained by hematocrit

An efficient method for multi-locus molecular haplotyping

Many methods exist for genotyping—revealing which alleles an individual carries at different genetic loci. A harder problem is haplotyping—determining which alleles lie on each of the two homologous chromosomes in a diploid individual. Conventional approaches to haplotyping require the use of several generations to reconstruct haplotypes within a pedigree, or use statistical methods to estimate the prevalence of different haplotypes in a population. Several molecular haplotyping methods have been proposed, but have been limited to small numbers of loci, usually over short distances. Here we demonstrate a method which allows rapid molecular haplotyping of many loci over long distances. The method requires no more genotypings than pedigree methods, but requires no family material. It relies on a procedure to identify and genotype single DNA molecules, and reconstruction of long haplotypes by a ‘tiling’ approach. We demonstrate this by resolving haplotypes in two regions of the human genome, harbouring 20 and 105 single-nucleotide polymorphisms, respectively. The method can be extended to reconstruct haplotypes of arbitrary complexity and length, and can make use of a variety of genotyping platforms. We also argue that this method is applicable in situations which are intractable to conventional approaches

Pulmonary MR angiography and perfusion imaging—A review of methods and applications

The pulmonary vasculature and its role in perfusion and gas exchange is an important consideration in many conditions of the lung and heart. Currently the mainstay of imaging of the vasculature and perfusion of the lungs lies with CT and nuclear medicine perfusion scans, both of which require ionizing radiation exposure. Improvements in MRI techniques have increased the use of MRI in pulmonary vascular imaging. Here we review MRI methods for imaging the pulmonary vasculature and pulmonary perfusion, both using contrast enhanced and non-contrast enhanced methodology. In many centres pulmonary MR angiography and dynamic contrast enhanced perfusion MRI are now well established in the routine workflow of patients particularly with pulmonary hypertension and thromboembolic disease. However, these imaging modalities offer exciting new directions for future research and clinical use in other respiratory diseases where consideration of pulmonary perfusion and gas exchange can provide insight in to pathophysiology

Discovering hidden relationships between renal diseases and regulated genes through 3D network visualizations

Abstract Background In a recent study, two-dimensional (2D) network layouts were used to visualize and quantitatively analyze the relationship between chronic renal diseases and regulated genes. The results revealed complex relationships between disease type, gene specificity, and gene regulation type, which led to important insights about the underlying biological pathways. Here we describe an attempt to extend our understanding of these complex relationships by reanalyzing the data using three-dimensional (3D) network layouts, displayed through 2D and 3D viewing methods. Findings The 3D network layout (displayed through the 3D viewing method) revealed that genes implicated in many diseases (non-specific genes) tended to be predominantly down-regulated, whereas genes regulated in a few diseases (disease-specific genes) tended to be up-regulated. This new global relationship was quantitatively validated through comparison to 1000 random permutations of networks of the same size and distribution. Our new finding appeared to be the result of using specific features of the 3D viewing method to analyze the 3D renal network. Conclusions The global relationship between gene regulation and gene specificity is the first clue from human studies that there exist common mechanisms across several renal diseases, which suggest hypotheses for the underlying mechanisms. Furthermore, the study suggests hypotheses for why the 3D visualization helped to make salient a new regularity that was difficult to detect in 2D. Future research that tests these hypotheses should enable a more systematic understanding of when and how to use 3D network visualizations to reveal complex regularities in biological networks.http://deepblue.lib.umich.edu/bitstream/2027.42/112972/1/13104_2010_Article_700.pd