Visible wavelength time-stretch optical coherence tomography.

Visible light optical coherence tomography (OCT) is an emerging non-invasive imaging modality that offers new opportunities for anatomical and functional imaging of biological tissues. Time-stretch dispersive Fourier transform, also known as photonic time-stretch, is an all-optical processing method that enables real-time Fourier transformation of ultrafast optical signals and allows for OCT at high A-scan rates. In this work, a working prototype of a photonic time-stretch OCT (TS-OCT) method in the visible wavelength region is proposed and experimentally demonstrated. The proposed visible-light TS-OCT system achieves unprecedented throughput of 100 giga voxels/second and OCT volume rate of 4,000 volumes/second and can be used to expand the range of applications of TS-OCT systems.

Spectral dynamics on saturable absorber in mode-locking with time stretch spectroscopy.

A mode-locked laser that can produce a broadband spectrum and ultrashort pulse has been applied for many applications in an extensive range of scientific fields. To obtain stable mode-locking during a long time alignment-free, a semiconductor saturable absorber is one of the most suitable devices. Dynamics from noise to a stable mode-locking state in the spectral-domain are known as complex and a non-repetitive phenomenon with the time scale from nanoseconds to milliseconds. Thus, a conventional spectrometer, which is composed of a grating and line sensor, cannot capture the spectral behavior from noise to stable mode-locking. As a powerful spectral measurement technique, a time-stretch dispersive Fourier transformation (TS-DFT) has been recently used to enable a successive single-shot spectral measurement over a couple of milliseconds time span. Here, we experimentally demonstrate real-time spectral evolution of femtosecond pulse build-up in a homemade passive mode-locked Yb fiber laser with a semiconductor saturable absorber mirror using TS-DFT. Capturing 700 consecutive spectra (~ 17 µs time window) in real-time using the time-stretch technique, we are able to resolve the transient dynamics that lead to stable mode-locking. Before setting stable mode-locking, an oscillating or shifting fringe pattern in the consecutive spectra was detected. This signature proves the existence of multiple pulses (including a soliton molecule) which is temporally separated with a different relative phase. The dynamics on multiple pulses is originated from a fast relaxation time of the saturable absorption effect. This study provides novel insights into understanding the pulse behavior during the birth of an ultrafast mode-locked laser pulse and the stable single-pulse operation which is highly stabilized.

HASLR: Fast Hybrid Assembly of Long Reads.

Third-generation sequencing technologies from companies such as Oxford Nanopore and Pacific Biosciences have paved the way for building more contiguous and potentially gap-free assemblies. The larger effective length of their reads has provided a means to overcome the challenges of short to mid-range repeats. Currently, accurate long read assemblers are computationally expensive, whereas faster methods are not as accurate. Moreover, despite recent advances in third-generation sequencing, researchers still tend to generate accurate short reads for many of the analysis tasks. Here, we present HASLR, a hybrid assembler that uses error-prone long reads together with high-quality short reads to efficiently generate accurate genome assemblies. Our experiments show that HASLR is not only the fastest assembler but also the one with the lowest number of misassemblies on most of the samples, while being on par with other assemblers in terms of contiguity and accuracy.

CircMiner: accurate and rapid detection of circular RNA through splice-aware pseudo-alignment scheme.

MOTIVATION: The ubiquitous abundance of circular RNAs (circRNAs) has been revealed by performing high-throughput sequencing in a variety of eukaryotes. circRNAs are related to some diseases, such as cancer in which they act as oncogenes or tumor-suppressors and, therefore, have the potential to be used as biomarkers or therapeutic targets. Accurate and rapid detection of circRNAs from short reads remains computationally challenging. This is due to the fact that identifying chimeric reads, which is essential for finding back-splice junctions, is a complex process. The sensitivity of discovery methods, to a high degree, relies on the underlying mapper that is used for finding chimeric reads. Furthermore, all the available circRNA discovery pipelines are resource intensive. RESULTS: We introduce CircMiner, a novel stand-alone circRNA detection method that rapidly identifies and filters out linear RNA sequencing reads and detects back-splice junctions. CircMiner employs a rapid pseudo-alignment technique to identify linear reads that originate from transcripts, genes or the genome. CircMiner further processes the remaining reads to identify the back-splice junctions and detect circRNAs with single-nucleotide resolution. We evaluated the efficacy of CircMiner using simulated datasets generated from known back-splice junctions and showed that CircMiner has superior accuracy and speed compared to the existing circRNA detection tools. Additionally, on two RNase R treated cell line datasets, CircMiner was able to detect most of consistent, high confidence circRNAs compared to untreated samples of the same cell line. AVAILABILITY AND IMPLEMENTATION: CircMiner is implemented in C++ and is available online at https://github.com/vpc-ccg/circminer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Identification of gene signature for treatment response to guide precision oncology in clear-cell renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC) is a common therapy resistant disease with aberrant angiogenic and immunosuppressive features. Patients with metastatic disease are treated with targeted therapies based on clinical features: low-risk patients are usually treated with anti-angiogenic drugs and intermediate/high-risk patients with immune therapy. However, there are no biomarkers available to guide treatment choice for these patients. A recently published phase II clinical trial observed a correlation between ccRCC patients' clustering and their response to targeted therapy. However, the clustering of these groups was not distinct. Here, we analyzed the gene expression profile of 469 ccRCC patients, using featured selection technique, and have developed a refined 66-gene signature for improved sub-classification of patients. Moreover, we have identified a novel comprehensive expression profile to distinguish between migratory stromal and immune cells. Furthermore, the proposed 66-gene signature was validated using a different cohort of 64 ccRCC patients. These findings are foundational for the development of reliable biomarkers that may guide treatment decision-making and improve therapy response in ccRCC patients.

Investigating Los Angeles' urban roadway network from a biologically-formed perspective.

The evolution of networks is constrained by spatial properties of the environment; a characterization that is true in both biological and built networks. Hence built networks such as urban streets can be compared to biological networks to reveal differences in efficiency and complexity. This study assessed foraging networks created by the slime-mold Physarium polycephalum on proportional 3D-printed topographic maps of metropolitan city of Los Angeles, California. Rapidly-generated isomorphic solutions were found to be consistently and statistically shorter than existing roadways in system length. Slime mold also allocated resources to supporting key nodes, analogous to how heavy traffic flows through major intersections. Further, chemical deterrents inhibited exploration of slime mold in selected areas and allows for testing of network redundancy and system resilience, such as after an earthquake or wildfire.

Structural variation and fusion detection using targeted sequencing data from circulating cell free DNA.

MOTIVATION: Cancer is a complex disease that involves rapidly evolving cells, often forming multiple distinct clones. In order to effectively understand progression of a patient-specific tumor, one needs to comprehensively sample tumor DNA at multiple time points, ideally obtained through inexpensive and minimally invasive techniques. Current sequencing technologies make the 'liquid biopsy' possible, which involves sampling a patient's blood or urine and sequencing the circulating cell free DNA (cfDNA). A certain percentage of this DNA originates from the tumor, known as circulating tumor DNA (ctDNA). The ratio of ctDNA may be extremely low in the sample, and the ctDNA may originate from multiple tumors or clones. These factors present unique challenges for applying existing tools and workflows to the analysis of ctDNA, especially in the detection of structural variations which rely on sufficient read coverage to be detectable. RESULTS: Here we introduce SViCT , a structural variation (SV) detection tool designed to handle the challenges associated with cfDNA analysis. SViCT can detect breakpoints and sequences of various structural variations including deletions, insertions, inversions, duplications and translocations. SViCT extracts discordant read pairs, one-end anchors and soft-clipped/split reads, assembles them into contigs, and re-maps contig intervals to a reference genome using an efficient k-mer indexing approach. The intervals are then joined using a combination of graph and greedy algorithms to identify specific structural variant signatures. We assessed the performance of SViCT and compared it to state-of-the-art tools using simulated cfDNA datasets with properties matching those of real cfDNA samples. The positive predictive value and sensitivity of our tool was superior to all the tested tools and reasonable performance was maintained down to the lowest dilution of 0.01% tumor DNA in simulated datasets. Additionally, SViCT was able to detect all known SVs in two real cfDNA reference datasets (at 0.6-5% ctDNA) and predict a novel structural variant in a prostate cancer cohort. AVAILABILITY: SViCT is available at https://github.com/vpc-ccg/svict. Contact:faraz.hach@ubc.ca.

Feature Enhancement in Visually Impaired Images.

One of the major open problems in computer vision is feature detection in visually impaired images. In this paper, we describe a potential solution using Phase Stretch Transform, a new computational approach for image analysis, edge detection and resolution enhancement that is inspired by the physics of the photonic time stretch technique. We mathematically derive the intrinsic nonlinear transfer function and demonstrate how it leads to (1) superior performance at low contrast levels and (2) a reconfigurable operator for hyper-dimensional classification. We prove that the Phase Stretch Transform equalizes the input image brightness across a range of intensities resulting in high dynamic range in visually impaired images. We also show further improvement in the dynamic range by combining our method with the conventional techniques. Finally, our results propose a new paradigm for the computation of mathematical derivatives via group delay dispersion operations.

Spectral periodicity in soliton explosions on a broadband mode-locked Yb fiber laser using time-stretch spectroscopy.

Experimentally, we demonstrate, to the best of our knowledge, the first observation of periodic spectrum changing via soliton explosion in a passively mode-locked fiber laser by a nonlinear polarization evolution. Using time stretch to capture 7220 consecutive single-shot spectra over a 100 µs time window in real time, the soliton explosions appear in a transition between two different mode-locking states. Simultaneous measurements of spectrum and pulse energy at three different output points in the laser cavity show that the soliton explosion's dynamics are related to residual dispersion. This study improves the understanding of pulse formation and evolution in the unstable mode-locking regime of lasers.

Time-bandwidth compression of microwave signals.

We report and demonstrate a reconfigurable photonic anamorphic stretch transform to realize time-bandwidth product (TBP) compression for microwave signals. A time-spectrum convolution system is employed to provide an ultra-high nonlinear dispersion up to several nanoseconds per gigahertz, which is required for processing nanosecond-long microwave signals. The group delay of the system can be engineered easily by programming a WaveShaper. Based on the proposed scheme, the TBP of a double pulse microwave signal is compressed by 1.9 times. Our proposal can provide a more efficient way to sample, digitize and store high-speed microwave signals, opening up entirely new perspectives for generation of many critical microwave signal processing modules.

Discovery and genotyping of novel sequence insertions in many sequenced individuals.

MOTIVATION: Despite recent advances in algorithms design to characterize structural variation using high-throughput short read sequencing (HTS) data, characterization of novel sequence insertions longer than the average read length remains a challenging task. This is mainly due to both computational difficulties and the complexities imposed by genomic repeats in generating reliable assemblies to accurately detect both the sequence content and the exact location of such insertions. Additionally, de novo genome assembly algorithms typically require a very high depth of coverage, which may be a limiting factor for most genome studies. Therefore, characterization of novel sequence insertions is not a routine part of most sequencing projects. RESULT: Here, we present Pamir, a new algorithm to efficiently and accurately discover and genotype novel sequence insertions using either single or multiple genome sequencing datasets. Pamir is able to detect breakpoint locations of the insertions and calculate their zygosity (i.e. heterozygous versus homozygous) by analyzing multiple sequence signatures, matching one-end-anchored sequences to small-scale de novo assemblies of unmapped reads, and conducting strand-aware local assembly. We test the efficacy of Pamir on both simulated and real data, and demonstrate its potential use in accurate and routine identification of novel sequence insertions in genome projects. AVAILABILITY AND IMPLEMENTATION: Pamir is available at https://github.com/vpc-ccg/pamir . CONTACT: fhach@{sfu.ca, prostatecentre.com } or calkan@cs.bilkent.edu.tr. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Soil flushing of cresols contaminated soil: application of nonionic and ionic surfactants under different pH and concentrations.

In this study, the viability of soil flushing on the removal of cresols (meta-, ortho-, and para-cresols) from contaminated soil has been investigated. High production and distribution of cresols in the environment indicate their potential for a widespread exposure to humans. The presence of these compounds in soil could cause a significant threat to environment, as they are toxic and refractory in nature. Cresols are persistent chemicals which are classified by the United State Environmental Protection Agency (U.S.EPA) as Group C, possible human carcinogens. Soil flushing is one of the soil remediation technologies which could by applied for treatment of hydrocarbon contaminated soil. Flushing of the contaminated soil samples was carried out by using sodium dodecyl sulfate (SDS) and Triton X-100 surfactant solutions at the concentrations of 0.1%, 0.2%, 0.3%, and 0.4% (W/W). Three acidic, neutral, and alkaline environments were utilized by adjusting pH of the washing solutions at 3, 7 and 12 to evaluate the effect of washing environment in removing cresols. The results of this research denote that the highest removal efficiencies of 79.6% and 83.51% were achieved for m-cresol and total o- and p-cresols, respectively, under the alkaline environment of pH12 at 0.4% (W/W) SDS concentration. Regarding performance of Triton X-100, the removal efficiencies of 80.26% and 80.14% for the above cresols were attained under similar conditions. Hence, illustrating the effectiveness of surfactants in soil flushing remediation of cresols contaminated soil.

Descemet stripping automated endothelial keratoplasty performed by cornea fellows.

PURPOSE: To evaluate the outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) in 78 eyes with corneal endothelial dysfunction performed by cornea fellows under the supervision of experienced faculty members in an academic hospital. METHODS: In this interventional case series, 78 eyes of 73 patients with corneal endothelial dysfunction of different underlying etiologies were enrolled for DSAEK. Healthy donor corneas with more than 2000 endothelial cells per square millimeter were requested. Intraoperative and postoperative complications were recorded. Best-corrected visual acuity, postoperative refraction, central corneal thickness, and endothelial cell density at 6 months after surgery were also registered and analyzed. RESULTS: Among 78 eyes of 73 patients with corneal endothelial dysfunction, DSAEK was performed on 55 eyes (70.5%) due to pseudophakic bullous keratopathy, which was the most common indication. Other indications included aphakic bullous keratopathy in 6 (7.7%), Fuchs endothelial dystrophy in 7 (8.9%), failed penetrating keratoplasty in 5 (6.4%), failed DSAEK in 3 (3.8%), and congenital hereditary endothelial dystrophy in 2 eyes (2.6%). All operations were performed by 4 cornea fellows supervised by the faculty members. Mean preoperative best-corrected visual acuity was 1.8 LogMAR, which improved to 0.77 LogMAR 6 months after the surgery. At this time, the mean central corneal thickness was 709.09 ± 109.24 µm and mean 6-month postoperative endothelial cell density was 1180 cells per square millimeter representing a mean cell loss of 61%, and mean spherical equivalent was +0.53 ± 1.83 diopter. Lenticule detachment was observed in 17 eyes (21.8%). Graft failure occurred in 8 eyes (10.2%). CONCLUSIONS: Outcomes of DSAEK performed by cornea fellows supervised by the faculty members seems to be fairly acceptable.

Review on the indigenous use and ethnopharmacology of hot and cold natures of phytomedicines in the Iranian traditional medicine

Objective: According to our best knowledge, this is the first and also a relatively comprehensive review on the cold and hot (or warm) nature of common Iranian traditional herbal medicines, based on the evidence-based and directly collected from the user and native-healers, instead of reviewing the classical texts of Iranian traditional medicine. This column resulted from a wide field study on the common Iranian traditional herbal medicine for their so-called effects of cold, hot and also balanced natures, used currently among ethno-pharmacologists, herbal-drug sellers and rural native-healers. Methods: The junior medical students were grouped into several groups for data collection. The information gathered from ethno-pharmacologists, herbal-drug sellers and rural native-healers, from different regions of Iran, especially Northwest, Southwest, Central and Northern provinces. For each repeated report of a certain indication, we added “a point” to the specification of that plant. If the number of every reported indication was, more than 5-20 times we reported that indication or pharmacological effect in our final report in this article.Results:The data recorded for every plant included: scientific name, family names, English name, Persian name, therapeutic nature (cold, hot or balanced), suggested actions and pharmacology, indication and usage, used parts/preparation, mode of administration. The plants were grouped into 25 families. Of a total 61 plants 16 were with cold (26%) and 43 were with hot nature (70%) and the rest were with balanced nature (4%). Conclusions: Almost of them have been long used as the components of the ancient receipts, hence, they may be more readily tried as suitable candidates in the future modern pharmacological investigations. Nevertheless, almost of them have been already evaluated in pharmacological laboratories, and their efficient properties have been confirmed. Considering the pharmacological properties of these plants, for finding a clear correlation of the pharmacological activities with the hot or cold nature, more detailed studies need to be conducted. Here we presented 61 plants currently used in Iranian traditional herbal medicine.

Ocular manifestations of transconjunctival heroin abuse: a case report of an unusual route of substance abuse.

PURPOSE: The purpose of this study was to present a patient with atypical corneoconjunctival lesions as a result of transconjunctival heroin abuse. METHODS: The authors conducted a prospective 8-month follow up of a 16-year-old girl who presented with bilateral atypical corneoconjunctival lesions. RESULTS: After a period of close observation, running diagnostic tests, and conservative treatment, the nature of the disease was suspected. Further discussion with the patient's family and her final confession revealed that she was using heroin through the conjunctiva. CONCLUSION: Substance abuse should be considered in the list of differential diagnoses in patients with an unusual presentation of ocular disease.