Modern interactive and data-intensive applications must operate under demanding time constraints, prompting a shift toward the adoption of specialized software and hardware network acceleration ...technologies. This specialization, however, poses significant scalability, flexibility, security, and economic sustainability challenges for application developers. Cloud computing holds the potential to overcome these obstacles by offering the cost-effective option to access specialized acceleration technologies through standard cloud interfaces. Nevertheless, that integration is still challenging for cloud providers. In the cloud, physical resources are hidden behind a virtualization layer, whereas acceleration technologies make applications directly interact with the hardware. To bridge this gap, recent literature explores the possibility of empowering cloud platforms with accelerated networking as a commodity, thus offering the innovative option of Network Acceleration as a Service. This survey reviews these recent research efforts by adopting popular technologies like XDP, DPDK, and RDMA as a reference. To organize the surveyed research in a comprehensive framework, we identify four key aspects that pose critical problems to the integration of acceleration options in cloud computing -access interfaces, virtualization techniques, serviceability, and security -and systematically discuss the associated challenges. Then, we present the issues to be further addressed and outline the most promising research directions for the full integration of network acceleration within next-generation cloud computing platforms.
X-linked dystonia parkinsonism (XDP) is a neurodegenerative disorder that has received significant interest on several fronts. Although much still remains to be elucidated regarding the disease ...cause, a robust amount of data has been produced in recent years compared to when it was first described in 1976. The debilitating nature of the overlapping dystonia and parkinsonism that characterizes this disorder has fueled much of the interest in unraveling its cause, clinical presentation, symptom progression, treatment and impact on the afflicted patients as well as their caregivers. Having made several significant advances in genetic studies, neuropathology, neurophysiology and clinical characterization, we are entering a new threshold in the study of this disorder, hopefully bringing us closer to potential treatments and possible cures. This review will focus on new information gathered regarding the motor and non-motor features of XDP, deep brain stimulation (DBS) as a potential treatment for XDP and the utility of the recently validated XDP-Movement Disorder Society of the Philippines (MDSP)-rating scale.
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•Improvement of drug loading into the pores of mesoporous silica.•Mechanistic loading aspects considering surface tension and dynamic viscosity.•Semi-volatile solvent mixtures as a ...novel preparation method of liquisolid systems.•Enhanced dissolution rate of poorly soluble drugs.
Despite the increasing interest in pharmaceutical use of mesoporous silica, there is still only limited knowledge on mechanisms of pore loading and subsequent drug desorption and release. Hence the aim of this work was to address the mechanistic aspects of drug loading into the mesoporous silica pores and to minimise the risk of pore clogging. Hydrophilic solvents (polysorbate 20 and polyethylene glycol 200) with high dissolving capacity for the model drug celecoxib were studied for their surface tension as well as dynamic viscosity by considering hydration. As an innovation in liquisolid systems preparation, a rather simple drug loading method on a mesoporous carrier was introduced by using semi-volatile solvent mixtures. Fast liquid loading into the pores was achieved due to the lowered viscosity and surface tension of the whole solvent system. Drug release kinetics suggested that lipid-based formulations belonging to class IV of Lipid Formulation Classification System may exhibit a lower risk of incomplete desorption from a carrier. The utilisation of volatile solvents during preparation had no negative impact on the liquisolid systems’ dissolution behaviour. All prepared formulations showed similar significantly faster dissolution profiles compared to the physical mixture. The novel approach has potential to promote liquisolid applications in pharmaceutics.
X-linked Dystonia-Parkinsonism (XDP) is a Mendelian neurodegenerative disease that is endemic to the Philippines and is associated with a founder haplotype. We integrated multiple genome and ...transcriptome assembly technologies to narrow the causal mutation to the TAF1 locus, which included a SINE-VNTR-Alu (SVA) retrotransposition into intron 32 of the gene. Transcriptome analyses identified decreased expression of the canonical cTAF1 transcript among XDP probands, and de novo assembly across multiple pluripotent stem-cell-derived neuronal lineages discovered aberrant TAF1 transcription that involved alternative splicing and intron retention (IR) in proximity to the SVA that was anti-correlated with overall TAF1 expression. CRISPR/Cas9 excision of the SVA rescued this XDP-specific transcriptional signature and normalized TAF1 expression in probands. These data suggest an SVA-mediated aberrant transcriptional mechanism associated with XDP and may provide a roadmap for layered technologies and integrated assembly-based analyses for other unsolved Mendelian disorders.
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•Genome assembly narrows the causal XDP locus to TAF1•An XDP-specific SVA insertion causes intron retention and reduced expression of TAF1•CRISPR/Cas9 excision of SVA rescues aberrant splicing and TAF1 expression in XDP•Expression profiling implicates neurodevelopment and dystonia pathways in XDP
A Mendelian form of dystonia arises from altered splicing and intron retention within a general transcription factor.
Segment Routing with IPv6 (SRv6) is a leading Hybrid SDN (HSDN) architecture, as it fully exploits standard IP routing and forwarding both in the control plane and in the data plane. In this paper we ...design, implement and evaluate a programmable data plane solution for Linux routers called HIKE (HybrId Kernel/eBPF forwarding), integrated in an HSDN/SRv6 architecture. HIKE integrates the conventional Linux kernel packet forwarding with custom designed eBPF/XDP (extended Berkeley Packet Filter/eXtreme Data Path) bypass to speed up performance of SRv6 software routers. Thus, in addition to the hybrid IP/SDN forwarding, we foster an additional hybrid approach inside a Linux forwarding engine combining eBPF/XDP and kernel based forwarding, taking the best from both worlds. Therefore, considering the two different conceptual levels of hybridization, we call our overall solution Hybrid squared or Hˆ2.
We have applied the Hˆ2 solution to Performance Monitoring (PM) in Hybrid SDNs, and we show how our HIKE data plane architecture supports SRv6 networking and Performance Monitoring (in particular Loss Monitoring) allowing a significant increase in performance: our implementation results show a remarkable throughput improvement (5x) with respect to a conventional Linux based solution.
X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease associated with an antisense insertion of a SINE-VNTR-Alu (SVA)-type retrotransposon within an intron of TAF1. This unique ...insertion coincides with six additional noncoding sequence changes in TAF1, the gene that encodes TATA-binding protein–associated factor-1, which appear to be inherited together as an identical haplotype in all reported cases. Here we examined the sequence of this SVA in XDP patients (n = 140) and detected polymorphic variation in the length of a hexanucleotide repeat domain, (CCCTCT)n. The number of repeats in these cases ranged from 35 to 52 and showed a highly significant inverse correlation with age at disease onset. Because other SVAs exhibit intrinsic promoter activity that depends in part on the hexameric domain, we assayed the transcriptional regulatory effects of varying hexameric lengths found in the unique XDP SVA retrotransposon using luciferase reporter constructs. When inserted sense or antisense to the luciferase reading frame, the XDP variants repressed or enhanced transcription, respectively, to an extent that appeared to vary with length of the hexamer. Further in silico analysis of this SVA sequence revealed multiple motifs predicted to form G-quadruplexes, with the greatest potential detected for the hexameric repeat domain. These data directly link sequence variation within the XDP-specific SVA sequence to phenotypic variability in clinical disease manifestation and provide insight into potential mechanisms by which this intronic retroelement may induce transcriptional interference in TAF1 expression.
Distributed training includes two important operations: gradient transmission and gradient aggregation, which will consume massive bandwidth and computing resources. To achieve efficient distributed ...training, one must overcome two critical challenges: heterogeneity of bandwidth resources and limitation of computing resources among compute nodes. Existing architectures based on Parameter Server (PS) and All-Reduce (AR) fail to cope with these challenges because the PS will aggregate gradients from all workers and suffers from bandwidth bottlenecks, while AR intends to alleviate bandwidth bottlenecks at the PS, but the workers need to process many gradient packets thus can be overloaded. To address these shortcomings, we design a new distributed training system called ALEPH. In the control plane, ALEPH uses an efficient algorithm to group workers into clusters with different sizes so as to fully utilize heterogeneous bandwidth. We show that the proposed algorithm can achieve a good approximation performance. In the data plane, ALEPH leverages, for the first time, extended Berkeley Packet Filter (eBPF) programs to aggregate and forward gradient packets to reduce computation overhead. We show how to overcome several hurdles in using eBPF for distributed training. We implement ALEPH and evaluate its performance on a small-scale testbed and large-scale simulations. Experimental results show that ALEPH reduces training time by 20%-31% and increases bandwidth utilization by 88% compared with state-of-the-art frameworks.
State-of-the-art approaches to design, develop and optimize software packet-processing programs are based on static compilation: the compiler's input is a description of the forwarding plane ...semantics and the output is a binary that can accommodate any control plane configuration or input traffic. In this paper, we demonstrate that tracking control plane actions and packet-level traffic dynamics at run time opens up new opportunities for code specialization. We present Morpheus, a system working alongside static compilers that continuously optimizes the targeted networking code. We introduce a number of new techniques, from static code analysis to adaptive code instrumentation, and we implement a toolbox of domain specific optimizations that are not restricted to a specific data plane framework or programming language. We apply Morpheus to several systems, from eBPF and DPDK programs including Katran, Meta's production-grade load balancer to container orchestration solutions such a Kubernets. We compare Morpheus to state-of-the-art optimization frameworks and show that it can bring up to 2x throughput improvement, while halving the 99th percentile latency.
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