130553 research outputs found
Sort by
A Network Segmentation Architecture for Flow Aggregation and DDoS Mitigation in SDN Using RAPID Flow Rules
No full textDistributed Denial-of-Service (DDoS) attacks have always posed a major threat to networks directly or as a cover for more sophisticated attacks. In recent years, with advances such as the large number of IoT nodes, amplifying platforms like Botnets-as-a-Service, etc., the number of DoS attacks has increased significantly, and the attacks have become more sophisticated. The new paradigm of Software-Defined Networking (SDN) enables a centralized view of the network, which has promising potential for efficient detection and mitigation of such attacks. This modern approach, however, exposes more areas of attack, such as Buffer Saturation, Link Flooding, Flow Table Overflow (FTO), and Controller Saturation. In this paper, we propose a novel, extremely lightweight, simple, yet effective, integrated approach, called Rapid Protection in Dataplane-DDoS (RAPID), for the detection and mitigation of several DoS attacks in SDN scenarios. Our approach couples the centralized view of the SDN networks with network segmentation based on the IP assignment, to generate a novel set of flow rules that can be used to manage the network in a way that allows for a smaller number of overall rules for proactively preventing FTO altogether while generating some novel statistics thereby adding the capability of fast detection and traceback of the origins of attacks to the controller. We evaluate the performance of the proposed scheme - RAPID - with Mininet and Ryu to demonstrate its effectiveness in detecting and mitigating several attacks while maintaining network performance
The inositol phosphate signalling network in physiology and disease
No full textCombinatorial substitution of phosphate groups on the inositol ring gives rise to a plethora of inositol phosphates (InsPs) and inositol pyrophosphates (PP-InsPs). These small molecules constitute an elaborate metabolic and signalling network that influences nearly every cellular function. This review delves into the knowledge accumulated over the past decades regarding the biochemical principles and significance of InsP metabolism. We focus on the biological actions of InsPs in mammals, with an emphasis on recent findings regarding specific target proteins. We further discuss the roles of InsP metabolism in contributing to physiological homeostasis and pathological conditions. A deeper understanding of InsPs and their metabolic pathways holds the potential to address unresolved questions and propel advances towards therapeutic applications
MCL-071 Bone marrow involvement and immunohistochemical profile in mantle cell lymphoma—experience from a North Indian Tertiary care center over 10 years
No full textContext:
A comprehensive analysis of pathological characteristics of mantle cell lymphoma in Indian patients is lacking.
Objective:
Primary objective was to evaluate bone marrow (BM) involvement and immunohistochemical (IHC) profile in Indian MCL patients. Secondary objective was assessing factors affecting OS and EFS.
Design, setting, and study participants
Ambispective analysis of clinicopathological data from 91 MCL patients diagnosed and treated between January 2013 and December 2023 at IRCH-AIIMS, New Delhi, India.
Outcomes measures:
Categorical, continuous variables summarized as frequency (percentage), median (range), respectively. STATA 13.0 assessed factors affecting OS and EFS in univariate and multivariate logistic regression (Cox proportional hazards model; adjusted hazard ratio [aHR], 95% CI). P value <.05 defined statistical significance.
Results:
Extranodal (EN) or BM involvement (73 cases [80.0%], 52 [57.0%]). Pattern (overlap): interstitial, 32 (62.0%); paratrabecular, 32 (62.0%); diffuse, 15 (29.0%). Gastrointestinal involvement: 18 (20.0%). Splenomegaly: 47 (52.0%). 40.0% (35/88) had atypical cells in peripheral blood (PB) by flow cytometry with simultaneous BM involvement. Fourteen (15.0%) had BM without PB involvement. Leukocytosis (TLC>10,000 cells/m3) in 33 (37.0%), anemia (Hb<10g/dL) in 26 (29.0%). Median LDH 304 U/L (range: 132-983 U/L); LDH ≥ ULN in 23 (25.0%). Histological variants: classical, 67 (75.0%); blastoid, 19 (21.0%); pleomorphic, 4 (4.0%). All cases were CD20+, CD3-. 20.0% (16/79) CD5-, 93.0% (70/75) CD23-. Three of 89 (3.0%) cyclin D1- and SOX11+. CD10, BCL-2, BCL-6 positivity in 2/74 (3.0%), 36/40 (90.0%), 4/48 (8.0%), respectively. Ki-67 ≥30% in 42/60 (70.0%). In univariate analysis, only anemia was significantly associated with poor OS and EFS; no association between EN involvement, LDH ≥ ULN, or pleomorphic/blastoid variants and outcomes. Leukocytosis was associated with poor EFS but not OS. In multivariate analysis, anemia was associated with poor EFS (aHR [95%CI]: 2.02 [1.15-3.55], P =.01).
Conclusions:
The first comprehensive analysis of pathological characteristics of MCL patients from India showed that over half had BM involvement, the most common being interstitial or paratrabecular pattern. Classical was the most frequent histological variant. One-fifth of cases were CD5- and 3% were cyclin D1-. Anemia was associated with poor OS and EFS in univariate analysis but only poor EFS in multivariate analysis
A Comparative Analysis of Deep Learning Architectures for Segmentation in Lung
No full textThis study explores the application of deep learning techniques to segment lung computed tomography (CT) scans, with a focus on cases involving COVID-19 and lung tumors. Utilizing a diverse dataset encompassing a wide range of CT scans, we conduct an extensive evaluation of various state-of-the-art deep neural network architectures. Our experimental results demonstrate the high efficiency and accuracy of deep learning models in performing image segmentation tasks, achieving impressive dice scores of 95.12% and 82.89% on COVID-19 and lung tumor data, respectively. These findings highlight the signif-icant potential of deep learning in medical imaging applications. Furthermore, we conduct thorough ablation studies, meticulously analyzing the performance of each network architecture. These studies provide valuable insights into the specific strengths and limitations of different deep learning approaches, facilitating the identification of the most effective methods for lung CT scan segmentation. This research not only underscores the promising capabilities of deep learning in medical image analysis but also offers a detailed understanding of how various models can be optimized to enhance performance in clinical applications
ATP‐independent assembly machinery of bacterial outer membranes: BAM complex structure and function set the stage for next‐generation therapeutics
No full textDiderm bacteria employ β-barrel outer membrane proteins (OMPs) as their first line of communication with their environment. These OMPs are assembled efficiently in the asymmetric outer membrane by the β-Barrel Assembly Machinery (BAM). The multi-subunit BAM complex comprises the transmembrane OMP BamA as its functional subunit, with associated lipoproteins (e.g., BamB/C/D/E/F, RmpM) varying across phyla and performing different regulatory roles. The ability of BAM complex to recognize and fold OM β-barrels of diverse sizes, and reproducibly execute their membrane insertion, is independent of electrochemical energy. Recent atomic structures, which captured BAM–substrate complexes, show the assembly function of BamA can be tailored, with different substrate types exhibiting different folding mechanisms. Here, we highlight common and unique features of its interactome. We discuss how this conserved protein complex has evolved the ability to effectively achieve the directed assembly of diverse OMPs of wide-ranging sizes (8–36 β-stranded monomers). Additionally, we discuss how darobactin—the first natural membrane protein inhibitor of Gram-negative bacteria identified in over five decades—selectively targets and specifically inhibits BamA. We conclude by deliberating how a detailed deduction of BAM complex—associated regulation of OMP biogenesis and OM remodeling will open avenues for the identification and development of effective next-generation therapeutics against Gram-negative pathogens
Leishmania protein KMP-11 modulates cholesterol transport and membrane fluidity to facilitate host cell invasion
No full textThe first step of successful infection by any intracellular pathogen relies on its ability to invade its host cell membrane. However, the detailed structural and molecular understanding underlying lipid membrane modification during pathogenic invasion remains unclear. In this study, we show that a specific Leishmania donovani (LD) protein, KMP-11, forms oligomers that bridge LD and host macrophage (MΦ) membranes. This KMP-11 induced interaction between LD and MΦ depends on the variations in cholesterol (CHOL) and ergosterol (ERG) contents in their respective membranes. These variations are crucial for the subsequent steps of invasion, including (a) the initial attachment, (b) CHOL transport from MΦ to LD, and (c) detachment of LD from the initial point of contact through a liquid ordered (Lo) to liquid disordered (Ld) membrane-phase transition. To validate the importance of KMP-11, we generate KMP-11 depleted LD, which failed to attach and invade host MΦ. Through tryptophan-scanning mutagenesis and synthesized peptides, we develop a generalized mathematical model, which demonstrates that the hydrophobic moment and the symmetry sequence code at the membrane interacting protein domain are key factors in facilitating the membrane phase transition and, consequently, the host cell infection process by Leishmania parasites
Multimode dispersion of light wave propagation in graded-index cladded fiber-optic cable
No full textAn optical fiber essentially consists of a transparent core medium with a thin cladding of a slightly less refractive index for total internal reflection of a passing signal of light. The material is usually homogeneous, but lately graded-index fiber cables are gaining increased application for greater efficiency in the propagation characteristics. Technology has evolved to furnish grading of the refractive index of the core to have different profiles. A parabolic profile of some degree α is often mentioned in texts (Keiser [7], p .63), but lately profiles of various other shapes, including nonsmooth steps (Cvijetic [1], p.35) have come in to usage for better wave guide action. A theoretical study of light waves propagating through such fibers is presented in this article, based strictly on the Maxwell equations of electromagnetism solved in terms of the single Hertz vector Π. The dispersion equation for the guided wave propagation is obtained in general terms from the theory. The method is first developed for the case of the parabolic profile and then extended to any general form of the refractive index. Numerical computation of the dispersion equation, for the first three modes in the parabolic case, with α = 2, show interestingly enough that the dispersion curves are pairs of segmented curves having opposite curvatures. A study of a non-smooth index fiber, like that of NZDSF, is also carried out from the general method developed, for which the dispersion equation does not show any dispersion whatsoever for the fundamental mode m = 0 - the purpose for which it is designed for practical use
Quasi-Classical Trajectory Calculations on a Two-State Potential Energy Surface Including Nonadiabatic Coupling Terms as Friction for D<sup>+</sup> + H<sub>2</sub> Collisions
No full textAkin to the traditional quasi-classical trajectory method for investigating the dynamics on a single adiabatic potential energy surface for an elementary chemical reaction, we carry out the dynamics on a 2-state ab initio potential energy surface including nonadiabatic coupling terms as friction terms for D+ + H2 collisions. It is shown that the resulting dynamics correctly accounts for nonreactive charge transfer, reactive non-charge transfer and reactive charge transfer processes. In addition, it leads to the formation of triatomic DH2+ species as well
Ly6G+Granulocytes-derived IL-17 limits protective host responses and promotes tuberculosis pathogenesis
No full textThe protective correlates of Mycobacterium tuberculosis ( Mtb ) infection-elicited host immune responses are incompletely understood. Here, we report pro-pathogenic crosstalk involving Ly6G + granulocytes (Ly6G + Gra), IL-17 and COX2. We show that in the lungs of Mtb -infected wildtype mice, either BCG-vaccinated or not, most intracellular bacilli are Ly6G + Gra-resident four weeks post-infection onwards. In the genetically susceptible IFNγ −/− mice, excessive Ly6G + Gra infiltration correlates with severe bacteraemia. Neutralizing IL-17 (anti-IL17mAb) and COX2 inhibition by celecoxib reverse Ly6G + Gra infiltration, associated pathology and death in IFNγ −/− mice. Surprisingly, Ly6G + Gra also serves as the major source of IL-17 in the lungs of Mtb -infected WT or IFNγ −/− mice. The IL-17-COX2-Ly6G + Gra interplay also operates in WT mice. Inhibiting RORγt, the key transcription factor for IL-17 production or COX2, reduces the bacterial burden in Ly6G + Gra, leading to reduced bacterial burden and pathology in the lungs of WT mice. In the Mtb -infected WT mice, COX2 inhibition abrogates IL-17 levels in the lung homogenates and significantly enhances BCG’s protective efficacy, mainly by targeting the Ly6G + Gra-resident Mtb pool. Furthermore, in pulmonary TB patients, high neutrophil count and IL-17 correlated with adverse treatment outcomes. Together, our results suggest that IL-17 and PGE2 are the negative correlates of protection, and we propose targeting the pro-pathogenic IL-17-COX2-Ly6G + Gra axis for TB prevention and therapy
2D Boron Nanosheets for Photo‐ and Electrocatalytic Applications
No full textBorophene, a new member of the two-dimensional (2D) materials family, has attracted researchers since its first experimental synthesis. Borophene (2D boron nanosheet) differs significantly from other 2D materials due to its low energy requirement to form defects, anisotropy, electron-deficient structure, multicentered bonding, etc. The uniqueness in properties of borophene compared to other 2D materials makes it suitable for applications in catalysis, sensing, energy storage, etc. The present review summarizes the development of borophene synthesis and emphasizes its applications in catalysis. Different synthesis approaches and their advantages and limitations are discussed briefly as substantial reviews are available on borophene synthesis. The applications of pristine borophene and their modified heterostructure in the field of catalysis were thoroughly reviewed, focusing on the electrocatalysis applications. Finally, the review discussed the future scope of borophene in designing new materials as well as opportunities to be utilized for other application fields. Since there is a lack of a good number of experimental reports on the applications of borophene and its derivatives, a huge opportunity is waiting for the researchers to explore the unknown world of borophene. In this regard, this review will help the researchers in an excellent manner