5,557 research outputs found

    NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo.

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    NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory proteins) are NLRs that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin and the inner rod and needle proteins of bacterial type III secretion systems (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific detection of bacterial ligands, genetic evidence has been lacking. Here we report the use of CRISPR/Cas9 to generate Naip1(-/-) and Naip2(-/-) mice, as well as Naip1-6(Δ/Δ) mice lacking all functional Naip genes. By challenging Naip1(-/-) or Naip2(-/-) mice with specific bacterial ligands in vivo, we demonstrate that Naip1 is uniquely required to detect T3SS needle protein and Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1 nor Naip2 is required for detection of flagellin. Previously generated Naip5(-/-) mice retain some residual responsiveness to flagellin in vivo, whereas Naip1-6(Δ/Δ) mice fail to respond to cytosolic flagellin, consistent with previous biochemical data implicating NAIP6 in flagellin detection. Our results provide genetic evidence that specific NAIP proteins function to detect specific bacterial proteins in vivo

    Rural development issues impacting the South

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    The question asked in this study is in what places in the South in 1992 were land prices low enough to make it feasible to expect at least a modest positive return on the implicit asset value of land. This report attempts to provide an approximate answer to that question by using crop enterprise budgets produced by Cooperative Extension agricultural economists in various Southern states to compute prototypical returns to land, management, and risk for various major commodities in each county in the South. We then compare those returns to the average per-acre value of farm real estate in the 1992 Census of Agriculture

    Infrared and Radio observations of a small group of protostellar objects in the molecular core, L1251-C

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    We present a multi-wavelength observational study of a low-mass star-forming region, L1251-C, with observational results at wavelengths from the near-infrared to the millimeter. Spitzer Space Telescope observations confirmed that IRAS 22343+7501 is a small group of protostellar objects. The extended emission to east-west direction with its intensity peak at the center of L1251A has been detected at 350 and 850 micron with the CSO and JCMT telescopes, tracing dense envelope materials around L1251A. The single-dish data from the KVN and TRAO telescopes show inconsistencies between the intensity peaks of several molecular line emission and that of the continuum emission, suggesting complex distributions of molecular abundances around L1251A. The SMA interferometer data, however, show intensity peaks of CO 2-1 and 13CO 2-1 located at the position of IRS 1, which is both the brightest source in IRAC image and the weakest source in the 1.3 mm dust continuum map. IRS 1 is the strongest candidate for the driving source of the newly detected compact CO 2-1 outflow. Over the whole region (14' by 14') of L125l-C, 3 Class I and 16 Class II sources have been detected, including three YSOs in L1251A. A comparison with the average projected distance among 19 YSOs in L1251-C and that among 3 YSOs in L1251A suggests L1251-C is an example of low-mass cluster formation, where protostellar objects are forming in a small group.Comment: 53 pages, 19 figures, accepted for publication in ApJ

    Effects of diabetes and hypertension on glomerular transforming growth factor-β receptor expression

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    Effects of diabetes and hypertension on glomerular transforming growth factor-β receptor expression.BackgroundSeveral studies have suggested that transforming growth factor-β1 (TGF-β1) is an important determinant of diabetic glomerular injury. TGF-β1 forms a heteromeric complex with two cellular receptor subtypes, designated TGF-β RII and TGF-β RI, but the effects of diabetes mellitus on glomerular TGF-β receptor expression have not been completely elucidated. We first compared the effect of experimental type I diabetes mellitus and uninephrectomy on glomerular TGF-β receptor expression in spontaneously hypertensive rats (SHRs), and then sought to determine whether changes in TGF-β receptor expression were strain specific by studying normotensive Wistar-Kyoto (WKY) rats.MethodsFive groups of male SHRs were studied. The first group received streptozotocin (60 mg/kg IV) and was studied after one week. The second group received streptozotocin and was studied after two weeks. The third group received streptozotocin (60 mg/kg IV) but received insulin to maintain euglycemia. The fourth group of age-matched SHRs served as the control group, while a fifth group of SHRs underwent uninephrectomy. Four groups of male WKY rats were also studied. The first group of WKY rats served as the age-matched control group. The second group of WKY rats received streptozotocin, while a third group of WKY rats underwent uninephrectomy. The fourth group underwent uninephrectomy and received streptozotocin. At each time point, glomeruli were isolated for protein extraction, and the protein was subjected to Western blot analysis of TGF-β RII and TGF-β RI expression.ResultsBasal expression of both TGF-β receptors per microgram of glomerular protein was similar in normotensive WKY rats and hypertensive SHRs. Hyperglycemia (blood glucose level, 17.8 ± 2.9 mmol/L) led to an early twofold increase in TGF-β RII protein expression and a fourfold increase in TGF-β RI protein expression in the glomeruli of hypertensive diabetic SHRs compared with euglycemic SHRs (blood glucose level, 5.8 ± 0.8 mmol/L), which was sustained after two weeks. Insulin treatment (blood glucose level, 5.2 ± 0.9 mmol/L) normalized both TGF-β RII and TGF-β RI expression in the glomeruli of SHRs that received streptozotocin. Glomerular capillary hypertension in the uninephrectomized SHRs led to a twofold increase in glomerular TGF-β RII protein expression, but did not reproduce the effect of diabetes mellitus on TGF-β RI expression. In contrast to the findings in SHRs, neither hyperglycemia (blood glucose level, 15.5 ± 2.1 mmol/L), uninephrectomy, nor hyperglycemia (blood glucose level, 16.8 ± 3.0 mmol/L) and uninephrectomy altered TGF-β receptor expression in the glomeruli of normotensive WKY rats.ConclusionThese studies support the hypothesis that hemodynamic factors and metabolic factors influence glomerular TGF-β receptor in vivo in the SHRs

    MalBoT-DRL: Malware botnet detection using deep reinforcement learning in IoT networks

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    In the dynamic landscape of cyber threats, multi-stage malware botnets have surfaced as significant threats of concern. These sophisticated threats can exploit Internet of Things (IoT) devices to undertake an array of cyberattacks, ranging from basic infections to complex operations such as phishing, cryptojacking, and distributed denial of service (DDoS) attacks. Existing machine learning solutions are often constrained by their limited generalizability across various datasets and their inability to adapt to the mutable patterns of malware attacks in real world environments, a challenge known as model drift. This limitation highlights the pressing need for adaptive Intrusion Detection Systems (IDS), capable of adjusting to evolving threat patterns and new or unseen attacks. This paper introduces MalBoT-DRL, a robust malware botnet detector using deep reinforcement learning. Designed to detect botnets throughout their entire lifecycle, MalBoT-DRL has better generalizability and offers a resilient solution to model drift. This model integrates damped incremental statistics with an attention rewards mechanism, a combination that has not been extensively explored in literature. This integration enables MalBoT-DRL to dynamically adapt to the ever-changing malware patterns within IoT environments. The performance of MalBoT-DRL has been validated via trace-driven experiments using two representative datasets, MedBIoT and N-BaIoT, resulting in exceptional average detection rates of 99.80% and 99.40% in the early and late detection phases, respectively. To the best of our knowledge, this work introduces one of the first studies to investigate the efficacy of reinforcement learning in enhancing the generalizability of IDS

    Properties of Multifunctional Hybrid Carbon Nanotube/Carbon Fiber Polymer Matrix Composites

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    For aircraft primary structures, carbon fiber reinforced polymer (CFRP) composites possess many advantages over conventional aluminum alloys due to their light weight, higher strength- and stiffness-to-weight ratios, and low life-cycle maintenance costs. However, the relatively low electrical and thermal conductivities of CFRP composites fail to provide structural safety in certain operational conditions such as lightning strikes. Carbon nanotubes (CNT) offer the potential to enhance the multi-functionality of composites with improved thermal and electrical conductivity. In this study, hybrid CNT/carbon fiber (CF) polymer composites were fabricated by interleaving layers of CNT sheets with Hexcel IM7/8852 prepreg. Resin concentrations from 1 wt% to 50 wt% were used to infuse the CNT sheets prior to composite fabrication. The interlaminar properties of the resulting hybrid composites were characterized by mode I and II fracture toughness testing. Fractographical analysis was performed to study the effect of resin concentration. In addition, multi-directional physical properties like thermal conductivity of the orthotropic hybrid polymer composite were evaluated
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