RLBWT Tricks

Until recently, most experts would probably have agreed we cannot backwards-step in constant time with a run-length compressed Burrows-Wheeler Transform (RLBWT), since doing so relies on rank queries on sparse bitvectors and those inherit lower bounds from predecessor queries. At ICALP '21, however, Nishimoto and Tabei described a new, simple and constant-time implementation. For a permutation $\pi$, it stores an $O (r)$-space table -- where $r$ is the number of positions $i$ where either $i = 0$ or $\pi (i + 1) \neq \pi (i) + 1$ -- that enables the computation of successive values of $\pi(i)$ by table look-ups and linear scans. Nishimoto and Tabei showed how to increase the number of rows in the table to bound the length of the linear scans such that the query time for computing $\pi(i)$ is constant while maintaining $O (r)$-space. In this paper we refine Nishimoto and Tabei's approach, including a time-space tradeoff, and experimentally evaluate different implementations demonstrating the practicality of part of their result. We show that even without adding rows to the table, in practice we almost always scan only a few entries during queries. We propose a decomposition scheme of the permutation $\pi$ corresponding to the LF-mapping that allows an improved compression of the data structure, while limiting the query time. We tested our implementation on real-world genomic datasets and found that without compression of the table, backward-stepping is drastically faster than with sparse bitvector implementations but, unfortunately, also uses drastically more space. After compression, backward-stepping is competitive both in time and space with the best existing implementations.Comment: 15 pages, 8 figures. New edition with expanded experimental results after poster acceptance at earlier conference. Section 4 removed, sections added for implementation detail

Augmented Thresholds for MONI

© 2023 IEEE. This version of the article has been accepted for publication, after peer review. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works. The Version of Record is available online at: https://doi.org/10.1109/DCC55655.2023.00035[Abstract]: MONI (Rossi et al., 2022) can store a pangenomic dataset T in small space and later, given a pattern P, quickly find the maximal exact matches (MEMs) of P with respect to T. In this paper we consider its one-pass version (Boucher et al., 2021), whose query times are dominated in our experiments by longest common extension (LCE) queries. We show how a small modification lets us avoid most of these queries which significantly speeds up MONI in practice while only slightly increasing its size.CMG, FSC and SL supported by CITIC, as Research Center accredited by Galician University System, funded by “Consellería de Cultura, Educación e Universidade from Xunta de Galicia”, supported 80% through ERDF Funds, ERDF Operational Programme Galicia 2014-2020, and the remaining 20% by “Secretaría Xeral de Universidades” (Grant ED431G 2019/01); Xunta de Galicia/ERDF under Grant [ED431C 2021/53]; GAIN/ERDF under Grant [IN852D 2021/3];Ministe-rio de Ciencia e Innovación MCIN/AEI/10.13039/501100011033 and “NextGenerationEU”/PRTR under Grants [TED2021-129245B-C21; PID2020-114635RB-I00; PDC2021-121239-C31; PID2019-105221RB-C41; RTI-2018-098309-B-C32]. NKB and TG supported by National Institutes of Health (NIH) NIAID (grant no. HG011392), the National Science Foundation NSF IIBR (grant no. 2029552) and the Natural Science and Engineering Research Council (NSERC) Discovery Grant (grant no. RGPIN-07185-2020) and a CGS-M scholarship. DK was supported by JSPS KAKENHI Grant Numbers JP22H03551, JP21K17701, and JP21H05847.Xunta de Galicia; ED431G 2019/01Xunta de Galicia; ED431C 2021/53Xunta de Galicia; IN852D 2021/3United States. National Institute of Allergy and Infectious Diseases; HG011392United States. National Science Foundation; 2029552Canada. Natural Science and Engineering Research Council; RGPIN-07185-2020Japan Society for the Promotion of Science; JP22H03551Japan Society for the Promotion of Science; JP21K17701Japan Society for the Promotion of Science; JP21H0584

Implementing a student-centered stroke intervention and prevention education program; evaluating motivation, cognitive load, and performance among middle school students

BackgroundIn this study, we investigated the association between motivation, cognitive load, difficulty, and performance in a stroke education outreach program implemented for middle school students.MethodsVarious interactive instructional activities were developed to engage students throughout the program to assess cognitive and intrinsic load arising from learner implementation of various tasks in a stroke education program for middle school kids. Performance was measured using a post-test to assess knowledge gained by the 6th, 7th, and 8th-grade middle school students. A short questionnaire was also administered to collect data on students’ motivation using the ARCS model to asses attention, relevance, confidence, and satisfaction. In addition, we evaluated difficulty level and cognitive load. The relationship between performance and motivation was assessed using Pearson’s correlation.ResultsIn our results, there was no significant difference (p > 0.05) in performance between the 6th, 7th, and 8th-grade students. The difference in performance, cognitive load (mental effort and difficulty), or motivation between the 6th, 7th, and 8 t-grade students was not significant (p > 0.05). The correlation between motivation and performance was significant (r = 0.87, p = 0.001), while the correlation between mental effort and performance was not significant (r = 0.34, p = 0.270). Also, the correlation between difficulty and performance was not significant (r = 0.38, p = 0.361). In the ARCS motivation model, attention, and confidence received the lowest mean scores (3.9), while relevance received the highest score (4.3).ConclusionOur findings reveal the importance of implementing novel activities to enhance students’ motivation to improve performance in the implementation of stroke education outreach programs for middle school students

Molecular Phenotypes Distinguish Patients with Relatively Stable from Progressive Idiopathic Pulmonary Fibrosis (IPF)

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic interstitial lung disease that is unresponsive to current therapy and often leads to death. However, the rate of disease progression differs among patients. We hypothesized that comparing the gene expression profiles between patients with stable disease and those in which the disease progressed rapidly will lead to biomarker discovery and contribute to the understanding of disease pathogenesis. METHODOLOGY AND PRINCIPAL FINDINGS: To begin to address this hypothesis, we applied Serial Analysis of Gene Expression (SAGE) to generate lung expression profiles from diagnostic surgical lung biopsies in 6 individuals with relatively stable (or slowly progressive) IPF and 6 individuals with progressive IPF (based on changes in DLCO and FVC over 12 months). Our results indicate that this comprehensive lung IPF SAGE transcriptome is distinct from normal lung tissue and other chronic lung diseases. To identify candidate markers of disease progression, we compared the IPF SAGE profiles in stable and progressive disease, and identified a set of 102 transcripts that were at least 5-fold up regulated and a set of 89 transcripts that were at least 5-fold down regulated in the progressive group (P-value</=0.05). The over expressed genes included surfactant protein A1, two members of the MAPK-EGR-1-HSP70 pathway that regulate cigarette-smoke induced inflammation, and Plunc (palate, lung and nasal epithelium associated), a gene not previously implicated in IPF. Interestingly, 26 of the up regulated genes are also increased in lung adenocarcinomas and have low or no expression in normal lung tissue. More importantly, we defined a SAGE molecular expression signature of 134 transcripts that sufficiently distinguished relatively stable from progressive IPF. CONCLUSIONS: These findings indicate that molecular signatures from lung parenchyma at the time of diagnosis could prove helpful in predicting the likelihood of disease progression or possibly understanding the biological activity of IPF

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria

Severe childhood malaria syndromes defined by plasma proteome profiles

BACKGROUND Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes. METHODS AND FINDINGS Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children. CONCLUSIONS We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes

Creating a Gold Medal Olympic and Paralympics Health Care Team: A Satisfaction Survey of the Mobile Medical Unit/Polyclinic Team Training for the Vancouver 2010 Winter Games

BACKGROUND: The mobile medical unit/polyclinic (MMU/PC) was an essential part of the medical services to support ill or injured Olympic or Paralympics family during the 2010 Olympic and Paralympics winter games. The objective of this study was to survey the satisfaction of the clinical staff that completed the training programs prior to deployment to the MMU. METHODS: Medical personnel who participated in at least one of the four training programs, including (1) week-end sessions; (2) web-based modules; (3) just-in-time training; and (4) daily simulation exercises were invited to participate in a web-based survey and comment on their level of satisfaction with training program. RESULTS: A total of 64 (out of 94 who were invited) physicians, nurses and respiratory therapists completed the survey. All participants reported favorably that the MMU/PC training positively impacted their knowledge, skills and team functions while deployed at the MMU/PC during the 2010 Olympic Games. However, components of the training program were valued differently depending on clinical job title, years of experience, and prior experience in large scale events. Respondents with little or no experience working in large scale events (45%) rated daily simulations as the most valuable component of the training program for strengthening competencies and knowledge in clinical skills for working in large scale events. CONCLUSION: The multi-phase MMU/PC training was found to be beneficial for preparing the medical team for the 2010 Winter Games. In particular this survey demonstrates the effectiveness of simulation training programs on teamwork competencies in ad hoc groups

Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced Arthritis and Pathology

ABSTRACT Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis and arthralgia over the past decade. These include a recent outbreak in the Caribbean islands and the Americas that caused more than 1 million cases of viral arthralgia. Despite the major impact of CHIKV on global health, viral determinants that promote CHIKV-induced disease are incompletely understood. Most CHIKV strains contain a conserved opal stop codon at the end of the viral nsP3 gene. However, CHIKV strains that encode an arginine codon in place of the opal stop codon have been described, and deep-sequencing analysis of a CHIKV isolate from the Caribbean identified both arginine and opal variants within this strain. Therefore, we hypothesized that the introduction of the arginine mutation in place of the opal termination codon may influence CHIKV virulence. We tested this by introducing the arginine mutation into a well-characterized infectious clone of a CHIKV strain from Sri Lanka and designated this virus Opal524R. This mutation did not impair viral replication kinetics in vitro or in vivo . Despite this, the Opal524R virus induced significantly less swelling, inflammation, and damage within the feet and ankles of infected mice. Further, we observed delayed induction of proinflammatory cytokines and chemokines, as well as reduced CD4 + T cell and NK cell recruitment compared to those in the parental strain. Therefore, the opal termination codon plays an important role in CHIKV pathogenesis, independently of effects on viral replication. IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes significant outbreaks of viral arthralgia. Studies with CHIKV and other alphaviruses demonstrated that the opal termination codon within nsP3 is highly conserved. However, some strains of CHIKV and other alphaviruses contain mutations in the opal termination codon. These mutations alter the virulence of related alphaviruses in mammalian and mosquito hosts. Here, we report that a clinical isolate of a CHIKV strain from the recent outbreak in the Caribbean islands contains a mixture of viruses encoding either the opal termination codon or an arginine mutation. Mutating the opal stop codon to an arginine residue attenuates CHIKV-induced disease in a mouse model. Compared to infection with the opal-containing parental virus, infection with the arginine mutant causes limited swelling and inflammation, as well as dampened recruitment of immune mediators of pathology, including CD4 + T cells and NK cells. We propose that the opal termination codon plays an essential role in the induction of severe CHIKV disease