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Thesis
Peer Reviewed

Unmanned Aerial Vehicle (UAV) is especially interesting among aircraft due its holonomic constraints, in other words, UAV can be capable of moving on 6-Degrees of freedom resulting in the possibility of landing and taking off vertically using their rotors to translate on Z-axis without moving on X-axis, unlike fixed-wing planes. Position and orientation estimation has been the focus of much research in recent decades. Onboard sensors widely utilized for such tasks include, but not limited, IMU, GPS, and a camera. In addition, since UAVs can operate in areas where the GPS isn't always available [ab], a vision sensor can be an important element of any autonomous system, and because of its adaptability a lot of information can be collected from only image frames to help with scene interpretation, navigation and pose estimation. Due to the incapability of monocular vision to perceive depth using a single image frame without any extra knowledge of the captured image, research has recently been done to estimate pose using multiple camera arrangements that rely on stereo disparity principle[ac][ad], which refers to the pixel location discrepancy when comparing object on overlapped images captured by different cameras, where object triangulation can be done since the distance between lenses is a well-known parameter, while other studies focus on compute disparity between image sequences using monocular vision[ae] and how disparity evolves in time. Because both techniques increase processing costs due to the complexity of image comparison, another branch of monocular vision research the use of cues on the captured image, that is, a reference point which dimensions were previously measured, as results a ratio between pixels and world units can be obtained and then target depth and distance estimation can be computed by comparison. Cues are not limited to knowing reference size; it is also possible to know cues geometry or even have numerous cues arranged on a well-known pattern or geometry, and use such fact to estimate target position and orientation. Furthermore, in environments where orientation and position play a crucial role, such as UAV landing, where it is expected that the UAV knows at all moment its position regarding the landing area, which, could or not has a constrained axis, that is, a 6 degrees of freedom landing area where translation and rotation is possible, there exist the need to develop reliable estimation methods that use sensors that are available to the UAV. For that reason, this thesis addresses the difficulty of computing the UAV relative height and absolute orientation of an Unmanned Surface Vehicle (USV) due to sea state 6 conditions, based primarily on a single image capture of n beacons, that is signal lights, arranged as a circular pattern around the center of the USV's deck, being image captured by a camera mounted on the UAV, which is hovering above the USV. The final objective is to be able to accurately estimate the dynamic state of the USV so that the UAV can land on the USV autonomously in up to sea state 6 conditions. This scenario is similar to landing on a dynamic terrestrial target, but with the added challenge of the sea's motion causing continuous USV translation and orientation.

Cover page: USV Attitude Position Estimation by a Hovering UAV Using Monocular Images of Deck-Mounted Lights

Article
Peer Reviewed

Transgender Female Youth and Sex Work: HIV Risk and a Comparison of Life Factors Related to Engagement in Sex Work

This study examined the HIV risk behaviors and life experiences of 151 transgender female youth, ages 15–24, in Los Angeles and Chicago. Descriptive analyses and logistic regression modeling were used to identify life factors associated with ever having engaged in sex work. Sixty-seven percent of participants had ever engaged in sex work and 19% self-reported being HIV positive. Many factors were significantly associated with sex work for this sample population. A final multivariate logistic regression model found that lower education status, homelessness, use of street drugs, and perceived social support remained significantly associated with sex work when controlling for other factors. Findings highlight the complex HIV risk environment and suggest a need for sex work initiation research for transgender female youth. HIV prevention efforts for this population need to include broad-based approaches that take into account individual, social, and community-level factors relevant to the lives of transgender female youth.

Article
Peer Reviewed

3D printed architected conducting polymer hydrogels

UC Merced Previously Published Works (2021)

Conducting polymer hydrogels combine electrical conductivity and tunable water content, rendering them strong candidates for a range of applications including biosensors, cell culture platforms, and energy storage devices. However, these hydrogels are mechanically brittle and prone to damage, prohibiting their use in emerging applications involving dynamic movement and large mechanical deformation. Here, we demonstrate that applying the concept of architecture to conducting polymer hydrogels can circumvent these impediments. A stereolithography 3D printing method is developed to successfully fabricate such hydrogels in complex lattice structures. The resulting hydrogels exhibit elastic compressibility, high fracture strain, enhanced cycling stability, and damage-tolerant properties despite their chemical composition being identical to their brittle, solid counterparts. Furthermore, concentrating the deformation to the 3D geometry, rather than polymer microstructure, effectively decouples the mechanical and electrical properties of the hydrogel lattices from their intrinsic properties associated with their chemical composition. The confluence of these new physical properties for conducting polymer hydrogels opens broad opportunities for a myriad of dynamic applications.

Cover page: 3D printed architected conducting polymer hydrogels

Article
Peer Reviewed

Deformation Rate‐Adaptive Conducting Polymers and Composites

UC Merced Previously Published Works (2023)

Materials are more easily damaged during accidents that involve rapid deformation. Here, a design strategy is described for electronic materials comprised of conducting polymers that defies this orthodox property, making their extensibility and toughness dynamically adaptive to deformation rates. This counterintuitive property is achieved through a morphology of interconnected nanoscopic core-shell micelles, where the chemical interactions are stronger within the shells than the cores. As a result, the interlinked shells retain material integrity under strain, while the rate of dissociation of the cores controls the extent of micelle elongation, which is a process that adapts to deformation rates. A prototype based on polyaniline shows a 7.5-fold increase in ultimate elongation and a 163-fold increase in toughness when deformed at increasing rates from 2.5 to 10 000% min^-1 . This concept can be generalized to other conducting polymers and highly conductive composites to create "self-protective" soft electronic materials with enhanced durability under dynamic movement or deformation.

Cover page: Deformation Rate‐Adaptive Conducting Polymers and Composites

Article
Peer Reviewed

DNA Microarray for Detection of Gastrointestinal Viruses

UC San Francisco Previously Published Works (2015)

Gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species, and an additional 5 species were validated using clinical samples. Detection limits of 1 × 10(3) virus particles of Human adenovirus C (HAdV), Human astrovirus (HAstV), and group A Rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased by one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%), and coinfection with more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by Anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), Human enterovirus (HEV) (9.2%), Human parechovirus (1.3%), Sapporo virus (1.3%), and Human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by reverse transcription-PCR (RT-PCR) detection of 5 gastrointestinal viruses. The RT-PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV, and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore, some discrepancies in detection of mixed infections were observed and were addressed by reverse transcription-quantitative PCR (RT-qPCR) of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant virus. The microarray described in this work should help in understanding the etiology of gastroenteritis in humans and animals.

Cover page: DNA Microarray for Detection of Gastrointestinal Viruses

Article
Peer Reviewed

An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo

LBL Publications (2024)

Background

Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan.

Methods

Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture.

Results

We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo.

Conclusions

Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.

Cover page: An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo

Article
Peer Reviewed

A cloud-compatible bioinformatics pipeline for ultrarapid pathogen identification from next-generation sequencing of clinical samples

UC San Francisco Previously Published Works (2014)

Unbiased next-generation sequencing (NGS) approaches enable comprehensive pathogen detection in the clinical microbiology laboratory and have numerous applications for public health surveillance, outbreak investigation, and the diagnosis of infectious diseases. However, practical deployment of the technology is hindered by the bioinformatics challenge of analyzing results accurately and in a clinically relevant timeframe. Here we describe SURPI ("sequence-based ultrarapid pathogen identification"), a computational pipeline for pathogen identification from complex metagenomic NGS data generated from clinical samples, and demonstrate use of the pipeline in the analysis of 237 clinical samples comprising more than 1.1 billion sequences. Deployable on both cloud-based and standalone servers, SURPI leverages two state-of-the-art aligners for accelerated analyses, SNAP and RAPSearch, which are as accurate as existing bioinformatics tools but orders of magnitude faster in performance. In fast mode, SURPI detects viruses and bacteria by scanning data sets of 7-500 million reads in 11 min to 5 h, while in comprehensive mode, all known microorganisms are identified, followed by de novo assembly and protein homology searches for divergent viruses in 50 min to 16 h. SURPI has also directly contributed to real-time microbial diagnosis in acutely ill patients, underscoring its potential key role in the development of unbiased NGS-based clinical assays in infectious diseases that demand rapid turnaround times.

Cover page: A cloud-compatible bioinformatics pipeline for ultrarapid pathogen identification from next-generation sequencing of clinical samples

Article
Peer Reviewed

Deciphering the Role of Mucosal Immune Responses and the Cervicovaginal Microbiome in Resistance to HIV Infection in HIV-Exposed Seronegative (HESN) Women

UC Davis Previously Published Works (2021)

The female genital tract (FGT) is an important site of human immunodeficiency virus (HIV) infection. Discerning the nature of HIV-specific local immune responses is crucial for identifying correlates of protection in HIV-exposed seronegative (HESN) individuals. The present study involved a comprehensive analysis of soluble immune mediators, secretory immunoglobulins (sIg), natural killer (NK) cells, CXCR5⁺ CD8⁺ T cells, T follicular helper (Tfh) cells, and T regulatory cells (Tregs) in the vaginal mucosa as well as the nature and composition of the cervicovaginal microbiome in HESN women. We found significantly elevated antiviral cytokines, soluble immunoglobulins, and increased frequencies of activated NK cells, CXCR5⁺ CD8⁺ T cells, and Tfh cells in HESN females compared to HIV-unexposed healthy (UH) women. Analysis of the genital microbiome of HESN women revealed a greater bacterial diversity and increased abundance of Gardnerella spp. in the mucosa. The findings suggest that the female genital tract of HESN females represents a microenvironment equipped with innate immune factors, antiviral mediators, and critical T cell subsets that protect against HIV infection. IMPORTANCE The vast majority of human immunodeficiency virus (HIV) infections across the world occur via the sexual route. The genital tract mucosa is thus the primary site of HIV replication, and discerning the nature of HIV-specific immune responses in this compartment is crucial. The role of the innate immune system at the mucosal level in exposed seronegative individuals and other HIV controllers remains largely unexplored. This understanding can provide valuable insights to improve vaccine design. We investigated mucosal T follicular helper (Tfh) cells, CXCR5⁺ CD8⁺ T cells, natural killer (NK) cells subsets, soluble immune markers, and microbiome diversity in HIV-exposed seronegative (HESN) women. We found a significantly higher level of mucosal CXCR5⁺ CD8⁺ T cells, CD4⁺ Tfh cells, activated NK cell subsets, and antiviral immune cell mediators in HESN women. We also found a higher abundance of Gardnerella spp., microbiome dysbiosis, and decreased levels of inflammatory markers to be associated with reduced susceptibility to HIV infection. Our findings indicate that increased distribution of mucosal NK cells, CXCR5⁺ CD8⁺ T cells, Tfh cells, and soluble markers in HIV controllers with a highly diverse cervicovaginal microbiome could contribute effectively to protection against HIV infection. Overall, our findings imply that future vaccine design should emphasize inducing these highly functional cell types at the mucosal sites.

Cover page: Deciphering the Role of Mucosal Immune Responses and the Cervicovaginal Microbiome in Resistance to HIV Infection in HIV-Exposed Seronegative (HESN) Women

Article
Peer Reviewed

Analysis of the ABCA4 genomic locus in Stargardt disease

UCLA Previously Published Works (2014)

Autosomal recessive Stargardt disease (STGD1, MIM 248200) is caused by mutations in the ABCA4 gene. Complete sequencing of ABCA4 in STGD patients identifies compound heterozygous or homozygous disease-associated alleles in 65-70% of patients and only one mutation in 15-20% of patients. This study was designed to find the missing disease-causing ABCA4 variation by a combination of next-generation sequencing (NGS), array-Comparative Genome Hybridization (aCGH) screening, familial segregation and in silico analyses. The entire 140 kb ABCA4 genomic locus was sequenced in 114 STGD patients with one known ABCA4 exonic mutation revealing, on average, 200 intronic variants per sample. Filtering of these data resulted in 141 candidates for new mutations. Two variants were detected in four samples, two in three samples, and 20 variants in two samples, the remaining 117 new variants were detected only once. Multimodal analysis suggested 12 new likely pathogenic intronic ABCA4 variants, some of which were specific to (isolated) ethnic groups. No copy number variation (large deletions and insertions) was detected in any patient suggesting that it is a very rare event in the ABCA4 locus. Many variants were excluded since they were not conserved in non-human primates, were frequent in African populations and, therefore, represented ancestral, and not disease-associated, variants. The sequence variability in the ABCA4 locus is extensive and the non-coding sequences do not harbor frequent mutations in STGD patients of European-American descent. Defining disease-associated alleles in the ABCA4 locus requires exceptionally well characterized large cohorts and extensive analyses by a combination of various approaches.

Cover page: Analysis of the ABCA4 genomic locus in Stargardt disease

Article
Peer Reviewed

The RAB39B p.G192R mutation causes X-linked dominant Parkinson’s disease

UC Irvine Previously Published Works (2015)

Objective

To identify the causal gene in a multi-incident U.S. kindred with Parkinson's disease (PD).

Methods

We characterized a family with a classical PD phenotype in which 7 individuals (5 males and 2 females) were affected with a mean age at onset of 46.1 years (range, 29-57 years). We performed whole exome sequencing on 4 affected and 1 unaffected family members. Sanger-sequencing was then used to verify and genotype all candidate variants in the remainder of the pedigree. Cultured cells transfected with wild-type or mutant constructs were used to characterize proteins of interest.

Results

We identified a missense mutation (c.574G > A; p.G192R) in the RAB39B gene that closely segregated with disease and exhibited X-linked dominant inheritance with reduced penetrance in females. The mutation occurred in a highly conserved amino acid residue and was not observed among 87,725 X chromosomes in the Exome Aggregation Consortium dataset. Sequencing of the RAB39B coding region in 587 familial PD cases yielded two additional mutations (c.428C > G [p.A143G] and c.624_626delGAG [p.R209del]) that were predicted to be deleterious in silico but occurred in families that were not sufficiently informative to assess segregation with disease. Experiments in PC12 and SK-N-BE(2)C cells demonstrated that p.G192R resulted in mislocalization of the mutant protein, possibly by altering the structure of the hypervariable C-terminal domain which mediates intracellular targeting.

Conclusions

Our findings implicate RAB39B, an essential regulator of vesicular-trafficking, in clinically typical PD. Further characterization of normal and aberrant RAB39B function might elucidate important mechanisms underlying neurodegeneration in PD and related disorders.

Cover page: The RAB39B p.G192R mutation causes X-linked dominant Parkinson’s disease