The use of HIV-1 DNA quantitation in cellular reservoirs to predict disease progression and treatment outcome in infected patients is hampered by the lack of standardization among the available ...methods. In the present study, real-time PCR methods used commonly for HIV-1 proviral DNA evaluation were compared, showing strong differences in the results, probably as a consequence of genome variability in the target regions. Standardization of HIV-1 proviral DNA quantitation assays is needed for use in clinical management of patients with HIV-1.
Modern user-facing applications deployed in datacenters use a distributed system architecture that exacerbates the latency requirements of their constituent microservices (30-250\mus). Existing CPU ...power-saving techniques degrade the performance of these applications due to the long transition latency (order of 100\mus) to wake up from a deep CPU idle state (C-state). For this reason, server vendors recommend only enabling shallow core C-states (e.g., CC1) for idle CPU cores, thus preventing the system from entering deep package C-states (e.g., PC6) when all CPU cores are idle. This choice, however, impairs server energy proportionality since power-hungry resources (e.g., IOs, uncore, DRAM) remain active even when there is no active core to use them. As we show, it is common for all cores to be idle due to the low average utilization (e.g., 5-20%) of datacenter servers running user-facing applications. We propose to reap this opportunity with AgilePkgC (APC), a new package C-state architecture that improves the energy proportionality of server processors running latency-critical applications. APC implements PC 1A (package C l agile), a new deep package C-state that a system can enter once all cores are in a shallow C-state (i.e., CC1) and has a nanosecond-scale transition latency. PC 1A is based on four key techniques. First, a hardware-based agile power management unit (APMU) rapidly detects when all cores enter a shallow core C-state (CC1) and triggers the system-level power savings control flow. Second, an IO Standby Mode (IOSM) places IO interfaces (e.g., PCIe, DMI, UPI, DRAM) in shallow (nanosecond-scale transition latency) low-power modes. Third, a CLM Retention (CLMR) mode rapidly reduces the CLM (Cache-and-home-agent, Last-level-cache, and Mesh network-on-chip) domain's voltage to its retention level, drastically reducing its power consumption. Fourth, APC keeps all system PLLs active in PC 1A to allow nanosecond-scale exit latency by avoiding PLL re-locking overhead. Combining these techniques enables significant power savings while requiring less than 200ns transition latency, \gt250\times faster than existing deep package C-states (e.g., PC6), making PC 1A practical for datacenter servers. Our evaluation based on an Intel Skylake-based server shows that APC reduces the energy consumption of Memcached by up to 41% (25% on average) with <0.1% performance degradation. APC provides similar benefits for other representative workloads.
Deploying real-time applications on multicores is challenging because tasks that are executed concurrently on different cores can interfere on shared resources, severely complicating worst-case ...timing analysis. To tackle this challenge, we propose a new scheduling model called isolation scheduling (IS): IS provides a framework to exploit multicores for real-time applications where tasks are grouped into classes. IS enforces mutually exclusive execution among different task classes, thus eliminating inter-class interference by construction. We assume that interference due to the statefulness of shared resources is either negligible or accounted for in the worst-case execution time of tasks. Mixed-criticality systems provide an example where IS is applicable. We propose and analyze two novel approaches for isolation scheduling: a
global
approach based on fluid scheduling and a
partitioned
approach based on hierarchical server scheduling, each with extensions to mixed-criticality applications. Through extensive simulations, we compare the two approaches in terms of schedulability and runtime overheads and quantify the schedulability loss due to the isolation constraint. Moreover, we conduct a comparative study among state-of-the-art approaches that comply with our IS model, showing that the new approaches can significantly outperform existing ones in terms of schedulability.
Weinhofer et al. reveal impaired plasticity of macrophages, with intrinsic pro-inflammatory skewing and a decreased ability to establish proper anti-inflammatory responses, in X-linked ...adrenoleukodystrophy (ALD). This may contribute to the rapidly progressive demyelination seen in cerebral ALD.
Abstract
X-linked adrenoleukodystrophy is caused by ATP-binding cassette transporter D1 (ABCD1) mutations and manifests by default as slowly progressive spinal cord axonopathy with associated demyelination (adrenomyloneuropathy). In 60% of male cases, however, X-linked adrenoleukodystrophy converts to devastating cerebral inflammation and demyelination (cerebral adrenoleukodystrophy) with infiltrating blood-derived monocytes and macrophages and cytotoxic T cells that can only be stopped by allogeneic haematopoietic stem cell transplantation or gene therapy at an early stage of the disease. Recently, we identified monocytes/macrophages but not T cells to be severely affected metabolically by ABCD1 deficiency. Here we found by whole transcriptome analysis that, although monocytes of patients with X-linked adrenoleukodystrophy have normal capacity for macrophage differentiation and phagocytosis, they are pro-inflammatory skewed also in patients with adrenomyloneuropathy in the absence of cerebral inflammation. Following lipopolysaccharide activation, the ingestion of myelin debris, normally triggering anti-inflammatory polarization, did not fully reverse the pro-inflammatory status of X-linked adrenoleukodystrophy macrophages. Immunohistochemistry on post-mortem cerebral adrenoleukodystrophy lesions reflected the activation pattern by prominent presence of enlarged lipid-laden macrophages strongly positive for the pro-inflammatory marker co-stimulatory molecule CD86. Comparative analyses of lesions with matching macrophage density in cases of cerebral adrenoleukodystrophy and acute multiple sclerosis showed a similar extent of pro-inflammatory activation but a striking reduction of anti-inflammatory mannose receptor (CD206) and haemoglobin-haptoglobin receptor (CD163) expression on cerebral adrenoleukodystrophy macrophages. Accordingly, ABCD1-deficiency leads to an impaired plasticity of macrophages that is reflected in incomplete establishment of anti-inflammatory responses, thus possibly contributing to the devastating rapidly progressive demyelination in cerebral adrenoleukodystrophy that only in rare cases arrests spontaneously. These findings emphasize monocytes/macrophages as crucial therapeutic targets for preventing or stopping myelin destruction in patients with X-linked adrenoleukodystrophy.
User-facing applications running in modern datacenters exhibit irregular request patterns and are implemented using a multitude of services with tight latency requirements (30-250\mus). These ...characteristics render existing energy-conserving techniques ineffective when processors are idle due to the long transition time (order of 100\mus) from a deep CPU core idle power state (C-state). While prior works propose management techniques to mitigate this inefficiency, we tackle it at its root with AgileWatts (AW): a new deep CPU core C-state architecture optimized for datacenter server processors targeting latency-sensitive applications.AW drastically reduces the transition latency from deep CPU core idle power states while retaining most of their power savings based on three key ideas. First, AW eliminates the latency (several microseconds) of savinglrestoring the core context when powering-off/-on the core in a deep idle state by i) implementing medium-grained power-gates, carefully distributed across the CPU core, and ii) reraining context in the power-ungated domain. Second, AW eliminates rhe flush latency (several tens of microseconds) of the LllL2 caches when entering a deep idle state by keeping LllL2 content power-ungated. A small control logic also remains ungated to serve cache coherence traffic. AW implements cache sleep-mode and leakage reduction for the power-ungated domain by lowering a core's voltage to the minimum operational level. Third, using a state-of-the-art power efficient all-digital phase-locked loop (ADPLL) clock generator, AW keeps the PLL active and locked during the idle state, cutting microseconds of wake-up latency at negligible power cost.Our evaluation with an accurate industrial-grade simulator calibrated against an Intel Skylake server shows that AW reduces the energy consumprion of Memcached by up to 71% (35% on average) with<1% end-to-end performance degradation. We observe similar trends for other evaluated services (MySQL and Kafka). AW's new deep C-states C6A and C6AE reduce transition-time by up to 900\times as compared to the deepest existing idle state C6, while consuming only 7% and 5% of the active state (C0) power, respectively.
Introduction Les fistules de la lame criblée sont des pathologies rares dont le traitement de choix est l’exclusion microchirurgicale. Avec l’avancée technique des micro-catheters et des agents ...emboliques, le traitement endovasculaire est une alternative thérapeutique grandissante. Nous présentons notre expérience endovasculaire pour ce type de fistule durale mettant en évidence les techniques choisies, leurs difficultés ainsi que les résultats cliniques et radiologiques. Patients et méthode Tous les patients avec une fistule durale de la lame criblée qui ont été traités dans notre service de 2008 à 2013 sont inclus. Nous avons revu rétrospectivement les données démographiques, cliniques et radiologiques ainsi que le type de traitement choisi pour chaque cas. Résultats Dix patients (M/F : 4/6, 51–73 ans) ont été traités par voie endovasculaire. Un traitement chirurgical a été nécessaire pour 2 patients. Sept cas sont de découverte fortuite, 2 ont présenté un saignement et 1 une crise comitiale. L’apport artériel est toujours par un ou plusieurs artères ethmoïdales (AE) (bilatéral dans 72,7 % des cas) associé à une artère méningée moyenne (AMM) dans 27,3 % des cas. Treize séances d’embolisation ont été réalisées dont 8 approches artérielles mono-pédiculaires (par AE dans 7 cas et AMM dans 1 cas), 3 approches artérielles bi-pédiculaires et 2 approches veineuses. Cinq des 7 approches par l’AE a permis de traiter la fistule. Pour les 2 autres cas, le produit embolique n’a pas pénétré le point de fistule nécessitant une approche veineuse. L’approche bi-pédiculaire a permis de traiter 2 cas sur 3 par embolisation via une AE après tentative par l’AMM. Pour le dernier cas, l’artère ophtalmique n’a pas pu être cathétérisée malgré l’utilisation d’un ballon et l’AMM était trop tortueuse. Chaque patient a bénéficié d’un examen ophtalmologique complet après le traitement n’objectivant aucun déficit. Huit des 10 cas ont été guéris par voie endovasculaire seule et 2 par méthode microchirurgicale. Conclusion Le traitement endovasculaire des fistules durales de la lame criblée est sûr et efficace avec un taux de succès de 80 % sans complication. L’embolisation par une artère ethmoïdale est la voie de choix. Les branches de l’AMM sont souvent tortueuses et ne permettent pas une bonne pénétration de l’agent embolique. La voie veineuse est efficace mais doit être réservée après échec de la voie artérielle.
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