ConnectIt: A Framework for Static and Incremental Parallel Graph Connectivity Algorithms

Connected components is a fundamental kernel in graph applications due to its usefulness in measuring how well-connected a graph is, as well as its use as subroutines in many other graph algorithms. The fastest existing parallel multicore algorithms for connectivity are based on some form of edge sampling and/or linking and compressing trees. However, many combinations of these design choices have been left unexplored. In this paper, we design the ConnectIt framework, which provides different sampling strategies as well as various tree linking and compression schemes. ConnectIt enables us to obtain several hundred new variants of connectivity algorithms, most of which extend to computing spanning forest. In addition to static graphs, we also extend ConnectIt to support mixes of insertions and connectivity queries in the concurrent setting. We present an experimental evaluation of ConnectIt on a 72-core machine, which we believe is the most comprehensive evaluation of parallel connectivity algorithms to date. Compared to a collection of state-of-the-art static multicore algorithms, we obtain an average speedup of 37.4x (2.36x average speedup over the fastest existing implementation for each graph). Using ConnectIt, we are able to compute connectivity on the largest publicly-available graph (with over 3.5 billion vertices and 128 billion edges) in under 10 seconds using a 72-core machine, providing a 3.1x speedup over the fastest existing connectivity result for this graph, in any computational setting. For our incremental algorithms, we show that our algorithms can ingest graph updates at up to several billion edges per second. Finally, to guide the user in selecting the best variants in ConnectIt for different situations, we provide a detailed analysis of the different strategies in terms of their work and locality

A New Reporter Vector System Based on Flow-Cytometry to Detect Promoter Activity

In this study, we report the development of a new dual reporter vector system for the analysis of promoter activity. This system employs green fluorescence emitting protein, EGFP, as a reporter, and uses red fluorescence emitting protein, DsRed, as a transfection control in a single vector. The expression of those two proteins can be readily detected via flow cytometry in a single analysis, with no need for any further manipulation after transfection. As this system allows for the simultaneous detection of both the control and reporter proteins in the same cells, only transfected cells which express the control protein, DsRed, can be subjected to promoter activity analysis, via the gating out of all un-transfected cells. This results in a dramatic increase in the promoter activity detection sensitivity. This novel reporter vector system should prove to be a simple and efficient method for the analysis of promoter activity

Specific Inhibition of Soluble γc Receptor Attenuates Collagen-Induced Arthritis by Modulating the Inflammatory T Cell Responses

IL-17 produced by Th17 cells has been implicated in the pathogenesis of rheumatoid arthritis (RA). It is important to prevent the differentiation of Th17 cells in RA. Homodimeric soluble γc (sγc) impairs IL-2 signaling and enhances Th17 differentiation. Thus, we aimed to block the functions of sγc by inhibiting the formation of homodimeric sγc. The homodimeric form of sγc was strikingly disturbed by sγc-binding DNA aptamer. Moreover, the aptamer effectively inhibited Th17 cell differentiation and restored IL-2 and IL-15 signaling impaired by sγc with evidences of increased survival of T cells. sγc was highly expressed in SF of RA patients and increased in established CIA mice. The therapeutic effect of PEG-aptamer was tested in CIA model and its treatment alleviated arthritis pathogenesis with impaired differentiation of pathogenic Th17, NKT1, and NKT17 cells in inflamed joint. Homodimeric sγc has pathogenic roles to exacerbate RA progression with differentiation of local Th17, NKT1, and NKT17 cells. Therefore, sγc is suggested as target of a therapeutic strategy for RA

Seeing Is Believing: Illuminating the Source of In Vivo Interleukin-7

Interleukin-7 (IL-7) is an essential cytokine for T cells. However, IL-7 is not produced by T cells themselves such that T cells are dependent on extrinsic IL-7. In fact, in the absence of IL-7, T cell development in the thymus as well as survival of naive T cells in the periphery is severely impaired. Furthermore, modulating IL-7 availability in vivo either by genetic means or other experimental approaches determines the size, composition and function of the T cell pool. Consequently, understanding IL-7 expression is critical for understanding T cell immunity. Until most recently, however, the spatiotemporal expression of in vivo IL-7 has remained obscured. Shortage of such information was partly due to scarce expression of IL-7 itself but mainly due to the lack of adequate reagents to monitor IL-7 expression in vivo. This situation dramatically changed with a recent rush of four independent studies that describe the generation and characterization of IL-7 reporter mice, all utilizing bacterial artificial chromosome transgene technology. The emerging consensus of these studies confirmed thymic stromal cells as the major producers of IL-7 but also identified IL-7 reporter activities in various peripheral tissues including skin, intestine and lymph nodes. Strikingly, developmental and environmental cues actively modulated IL-7 reporter activities in vivo suggesting that IL-7 regulation might be a new mechanism of shaping T cell development and homeostasis. Collectively, the availability of these new tools opens up new venues to assess unanswered questions in IL-7 biology in T cells and beyond

New insight of square stepping exercise in immune fine-tuning for anticipating emerging pandemics

ABSTRACTThe COVID-19 pandemic has significantly impacted human life, posing serious physical and psychological threats, particularly to the elderly. While individuals of all ages are susceptible to contracting COVID-19, older people face a heightened risk of developing various diseases due to age-related immunophysiological changes and preexisting health conditions. The interplay between immune health and physical activity is believed to hold even greater significance during a pandemic. Recent findings from our research indicate that the intervention of square stepping exercise (SSE), characterized by a rhythmic and controlled stepping pattern, resulted in increased levels of Brain-Derived Neurotrophic Factor (BDNF) in the elderly. BDNF, known to influence not only nerve cells but also immune cells, suggests a potential link between SSE and immune system modulation. Consequently, this exercise regimen holds promise in counteracting age-related immunophysiological changes, fine-tuning immune responses, and mitigating the severity of potential new virus outcomes, such as ‘Disease X.’ This review aims to underscore the significance of integrating SSE as a home-based program, serving as a potent tool to enhance immune resilience, prepare for future potential pandemics, and empower older individuals during challenging times. Through the practice of SSE, older adults may strengthen their ability to navigate the challenges posed by pandemics and maintain a sense of control over their well-being

Altitudinal range-size distribution of breeding birds and environmental factors for the determination of species richness: An empirical test of altitudinal Rapoport's rule and non-directional rescue effect on a local scale.

Range-size distributions are important for understanding species richness patterns and led to the development of the controversial Rapoport's rule and Rapoport-rescue effect. This study aimed to understand the relationship between species richness and range-size distribution in relation to environmental factors. The present study tested the following: (1) altitudinal Rapoport's rule, and a subsequent test on climatic and ambient energy hypotheses, (2) non-directional rescue effect, and a subsequent test on effect of environmental factors associated with the distribution of narrowest to widest-range species. Altitudinal species range-size distribution increased with increasing altitude and showed a negative relationship with climatic variables. These results support the altitudinal Rapoport's rule and climatic hypothesis; however, they do not fully support the ambient energy hypothesis. Results from testing the non-directional rescue effect showed that the inflow intensity of species from both directions (high and low elevations) affected species richness. And we found that the species with intermediate range-size, rather than narrowest or widest range-size were the main cause of a mid-peak of species richness and the non-directional rescue effect. Additionally, the richness of species with intermediate range-size was highly related to minimum temperature, habitat heterogeneity, or primary productivity. Although altitudinal range-size distribution results were similar to the phenomenon of altitudinal Rapoport's rule, the mid-peak pattern of species richness could not be explained by the underlying mechanism of Rapoport's-rescue effect; however, the non-directional rescue effect could explain a mid-peak pattern of species richness along altitudinal gradient

The Potential Role of a Soluble γ-Chain Cytokine Receptor as a Regulator of IL-7-Induced Lymphoproliferative Disorders

IL-7 is an essential, nonredundant growth factor for T and B cell generation and maintenance. While IL-7 deficiency results in lymphopenia, overexpression of IL-7 can cause neoplasia in experimental models. IL-7’s involvement in neoplasia has been appreciated through studies of IL-7 transgenic (Tg) mice models and human lymphoma patients. Since we recently found that a soluble form of the common γ-chain (γc) cytokine receptor (sγc) antagonistically regulates IL-7 signaling, IL-7 and sγc double-Tg mice were generated to investigate the effects of sγc overexpression in IL-7-mediated lymphoproliferative disorders (LPDs). The overexpression of sγc prevents IL-7Tg-induced abnormal increase of LN cell numbers and the development of splenomegaly, resulting in striking amelioration of mortality and disease development. These results suggest that modification of γc cytokine responsiveness by sγc molecules might control various γc cytokine-associated hematologic malignancy, and also provide an alternative view to approach antitumor therapy