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  1. Diffusion State Distance (DSD) is a data-dependent metric that compares data points using a data-driven diffusion process and provides a powerful tool for learning the underlying structure of high-dimensional data. While finding the exact nearest neighbors in the DSD metric is computationally expensive, in this paper, we propose a new random-walk based algorithm that empirically finds approximate k-nearest neighbors accurately in an efficient manner. Numerical results for real-world protein-protein interaction networks are presented to illustrate the efficiency and robustness of the proposed algorithm. The set of approximate k-nearest neighbors performs well when used to predict proteins’ functional labels.
    Free, publicly-accessible full text available March 18, 2023
  2. Background While increased CD8 counts and low CD4/CD8 ratio during treated HIV correlate with immunosenescence, their additional predictive values to identify individuals with HIV at higher risk of clinical events remain controversial. Methods We selected treatment-naive individuals initiating ART from ACTG studies 384, 388, A5095, A5142, A5202, and A5257 who had achieved viral suppression at year 2. We examined the effect of CD8+ T cell counts and CD4/CD8 at year 2 on the probability of AIDS and serious non-AIDS events in years 37. We used inverse probability weighting methods to address informative censoring, combined with multivariable logistic regression models. Findings We analyzed 5133 participants with a median age of 38 years; 959 (19%) were female, pre-ART median CD4 counts were 249 (Q1-Q3 91372) cell/µL. Compared to participants with CD8 counts between 500/µL and 1499/µL, those with >1500/µL had a higher risk of clinical events during years 37 (aOR 1.75; 95%CI 1.332.32). CD4/CD8 ratio was not predictive of greater risk of events through year 7. Additional analyses revealed consistent CD8 count effect sizes for the risk of AIDS events and noninfectious non-AIDS events, but opposite effects for the risk of severe infections, which were more frequent among individuals with CD8 countsmore »<500/µL (aOR 1.70; 95%CI 1.092.65). Interpretation The results of this analysis with pooled data from clinical trials support the value of the CD8 count as a predictor of clinical progression. People with very high CD8 counts during suppressive ART might benefit from closer monitoring and may be a target population for novel interventions.« less
    Free, publicly-accessible full text available April 1, 2023
  3. Free, publicly-accessible full text available April 25, 2023
  4. Free, publicly-accessible full text available April 25, 2023
  5. We describe WiSER, a clean-slate search engine designed to exploit high-performance SSDs with the philosophy "read as needed". WiSER utilizes many techniques to deliver high throughput and low latency with a relatively small amount of main memory; the techniques include an optimized data layout, a novel two-way cost-aware Bloom filter, adaptive prefetching, and space-time trade-offs. In a system with memory that is significantly smaller than the working set, these techniques increase storage space usage (up to 50%), but reduce read amplification by up to 3x, increase query throughput by up to 2.7x, and reduce latency by 16x when compared to the state-of-the-art Elasticsearch. We believe that the philosophy of "read as needed" can be applied to more applications as the read performance of storage devices keeps improving.
  6. A bio-orthogonal chemistry-based approach for fluorescent labelling of ribosomal RNA is described. It involves an adenosine analogue modified with trans -cyclooctene and masked 5′-phosphate group using aryl phosphoramidate. The incorporation into rRNA has been confirmed using agarose gel electrophoresis, as well as a highly sensitive UHPLC-MS/MS method. Fluorescent labelling of rRNA has been achieved in live HeLa cells via an inverse electron demand Diels–Alder reaction with a tetrazine conjugated to an Oregon Green fluorophore. This communication describes the stepwise approach that led to the development and characterization of the probe. The results demonstrate a new strategy towards development of future fluorescent probes to investigate the biochemistry of nucleic acids.