Dual-band infrared imaging applications: locating buried minefields, mapping sea ice and inspecting aging aircraft

We discuss the use of dual-band infrared (DBIR) imaging for three quantitative NDE applications: locating buried surrogate mines, mapping sea ice thicknesses and inspecting subsurface flaws in aging aircraft parts. Our system of DBIR imaging offers a unique combination of thermal resolution, detectability, and interpretability. Pioneered at Lawrence Livermore Laboratory, it resolves 0.2 °C differences in surface temperatures needed to identify buried mine sites and distinguish them from surface features. It produces both surface temperature and emissivity-ratio images of sea ice, needed to accurately map ice thicknesses (e.g., by first removing clutter due to snow and surface roughness effects). The DBIR imaging technique depicts subsurface flaws in composite patches and lap joints of aircraft, thus providing a needed tool for aging aircraft inspections

Comparison Between Spectral-Domain and Swept-Source Optical Coherence Tomography Angiographic Imaging of Choroidal Neovascularization

PURPOSE. The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA). METHODS. Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 x 3-and 6 x 6-mm(2) scans were obtained on both instruments. The 3 x 3-mm(2) SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 x 6-mm(2) SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 x 3-mm(2) scans and twice in the 6 x 6-mm(2) scans. Choroidal neovascularization was excluded if not fully contained within the 3 x 3-mm(2) scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. RESULTS. Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 x 3-mm(2) scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm(2), respectively (P = 0.047). For the 6 x 6-mm(2) scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm(2) (P = 0.003). CONCLUSIONS. The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 x 6-mm(2) scans.Carl Zeiss Meditec, Inc.National Eye InstituteResearch to Prevent Blindness, Inc. (New York, NY)National Eye Institute Center Core GrantCAPES Foundation, Ministry of Education of Brazil (Brasilia, Brazil)German Research FoundationUniv Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilUniv Washington, Dept Bioengn, Seattle, WA 98195 USACarl Zeiss Meditec Inc, Adv Dev, Dublin, CA USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilNational Eye Institute: R01EY024158National Eye Institute Center Core Grant: P30EY014801German Research Foundation: SCHA 1869/1-1Web of Scienc

Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms

PURPOSE. To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. METHODS. Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 x 3-mm and 6 x 6-mm scans. The complex optical microangiography (OMAG(C)) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 mu m below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. RESULTS. Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 x 3-mm (P = 0.61, paired t-test) and 6 x 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 x 3-mm (P = 0.41, paired t-test) and 6 x 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 3 3-mm scans (P = 0.011, paired sample t-test) and the 6 x 6-mm scans (P = 0.021, paired t-test). CONCLUSIONS. The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.Carl Zeiss Meditec, Inc. (Dublin, CA)National Eye InstituteResearch to Prevent Blindness, Inc., New York, New YorkNational Eye Institute Center Core GrantCAPES Foundation, Ministry of Education of Brazil, Brasilia-BrazilGerman Research Foundation (DFG)Research to Prevent BlindnessUniv Washington, Dept Bioengn, 3720 NE 15th Ave, Seattle, WA 98195 USAUniv Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilCarl Zeiss Meditec Inc, Adv Dev, Dublin, CA USAUniv Washington, Dept Ophthalmol, 3720 NE 15th Ave, Seattle, WA 98195 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilNational Eye Institute: R01EY024158National Eye Institute Center Core Grant: P30EY014801German Research Foundation (DFG): SCHA 1869/1-1Web of Scienc

More Than 1,001 Problems with Protein Domain Databases: Transmembrane Regions, Signal Peptides and the Issue of Sequence Homology

Large-scale genome sequencing gained general importance for life science because functional annotation of otherwise experimentally uncharacterized sequences is made possible by the theory of biomolecular sequence homology. Historically, the paradigm of similarity of protein sequences implying common structure, function and ancestry was generalized based on studies of globular domains. Having the same fold imposes strict conditions over the packing in the hydrophobic core requiring similarity of hydrophobic patterns. The implications of sequence similarity among non-globular protein segments have not been studied to the same extent; nevertheless, homology considerations are silently extended for them. This appears especially detrimental in the case of transmembrane helices (TMs) and signal peptides (SPs) where sequence similarity is necessarily a consequence of physical requirements rather than common ancestry. Thus, matching of SPs/TMs creates the illusion of matching hydrophobic cores. Therefore, inclusion of SPs/TMs into domain models can give rise to wrong annotations. More than 1001 domains among the 10,340 models of Pfam release 23 and 18 domains of SMART version 6 (out of 809) contain SP/TM regions. As expected, fragment-mode HMM searches generate promiscuous hits limited to solely the SP/TM part among clearly unrelated proteins. More worryingly, we show explicit examples that the scores of clearly false-positive hits, even in global-mode searches, can be elevated into the significance range just by matching the hydrophobic runs. In the PIR iProClass database v3.74 using conservative criteria, we find that at least between 2.1% and 13.6% of its annotated Pfam hits appear unjustified for a set of validated domain models. Thus, false-positive domain hits enforced by SP/TM regions can lead to dramatic annotation errors where the hit has nothing in common with the problematic domain model except the SP/TM region itself. We suggest a workflow of flagging problematic hits arising from SP/TM-containing models for critical reconsideration by annotation users

Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans

A complete understanding of the factors that determine selection of antigens recognized by the humoral immune response following infectious agent challenge is lacking. Here we illustrate a systems biology approach to identify the antibody signature associated with Brucella melitensis (Bm) infection in humans and predict proteomic features of serodiagnostic antigens. By taking advantage of a full proteome microarray expressing previously cloned 1406 and newly cloned 1640 Bm genes, we were able to identify 122 immunodominant antigens and 33 serodiagnostic antigens. The reactive antigens were then classified according to annotated functional features (COGs), computationally predicted features (e.g., subcellular localization, physical properties), and protein expression estimated by mass spectrometry (MS). Enrichment analyses indicated that membrane association and secretion were significant enriching features of the reactive antigens, as were proteins predicted to have a signal peptide, a single transmembrane domain, and outer membrane or periplasmic location. These features accounted for 67% of the serodiagnostic antigens. An overlay of the seroreactive antigen set with proteomic data sets generated by MS identified an additional 24%, suggesting that protein expression in bacteria is an additional determinant in the induction of Brucella-specific antibodies. This analysis indicates that one-third of the proteome contains enriching features that account for 91% of the antigens recognized, and after B. melitensis infection the immune system develops significant antibody titers against 10% of the proteins with these enriching features. This systems biology approach provides an empirical basis for understanding the breadth and specificity of the immune response to B. melitensis and a new framework for comparing the humoral responses against other microorganisms

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport

Tiina Paunio on työryhmän UK10K jäsen.The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions.Peer reviewe

Widefield En Face Optical Coherence Tomography Imaging of Subretinal Drusenoid Deposits

To determine whether subretinal drusenoid deposits (SDD) can be detected on widefield en face slab images derived from spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) volume scans. Retrospective study of patients with dry age-related macular degeneration (AMD) enrolled prospectively in an OCT imaging study using SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA) with a central wavelength of 840 nm, and a prototype 100-kHz SS-OCT instrument (Carl Zeiss Meditec) with a central wavelength of 1,050 nm. Seven en face slabs were evaluated with thicknesses from 20 to 55 µm and positioned at distances up to 55 µm above the retinal pigment epithelium (RPE). A montage of 6 × 6 mm SD-OCT en face images of the posterior pole from each patient was compared with a 9 × 12 mm SS-OCT single en face slab image and with color, autofluorescence, and infrared reflectance images. A total of 160 patients (256 eyes) underwent scanning with both OCT instruments; 57 patients (95 eyes) also underwent multimodal fundus imaging. Of 95 eyes, 32 (34%) were diagnosed with reticular pseudodrusen (RPD) using multimodal imaging. All eyes with RPD demonstrated a pattern of SDD on widefield en face OCT similar to that observed for RPD. The en face slab image that consistently identified SDD was the 20-µm thick slab with boundaries from 35 to 55 µm above the RPE. Widefield en face slab imaging with SD-OCT and SS-OCT can detect SDD and could replace multimodal imaging for the diagnosis of RPD in the future