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Ray Neiheiser, Miguel Matos, Luís Rodrigues
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483584

Abstract:
With the growing commercial interest in blockchains, permissioned implementations have received increasing attention. Unfortunately, the BFT consensus algorithms that are the backbone of most of these blockchains scale poorly and offer limited throughput. Many state-of-the-art algorithms require a single leader process to receive and validate votes from a quorum of processes and then broadcast the result, which is inherently non-scalable. Recent approaches avoid this bottleneck by using dissemination/aggregation trees to propagate values and collect and validate votes. However, the use of trees increases the round latency, which ultimately limits the throughput for deeper trees. In this paper we propose Kauri, a BFT communication abstraction that can sustain high throughput as the system size grows, leveraging a novel pipelining technique to perform scalable dissemination and aggregation on trees. Our evaluation shows that Kauri outperforms the throughput of state-of-the-art permissioned blockchain protocols, such as HotStuff, by up to 28x. Interestingly, in many scenarios, the parallelization provided by Kauri can also decrease the latency.
Rafael Lourenco de Lima Chehab, Antonio Paolillo, Diogo Behrens, Ming Fu, Hermann Härtig, Haibo Chen
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483557

Abstract:
Efficient locking mechanisms are extremely important to support large-scale concurrency and exploit the performance promises of many-core servers. Implementing an efficient, generic, and correct lock is very challenging due to the differences between various NUMA architectures. The performance impact of architectural/NUMA hierarchy differences between x86 and Armv8 are not yet fully explored, leading to unexpected performance when simply porting NUMA-aware locks from x86 to Armv8. Moreover, due to the Armv8 Weak Memory Model (WMM), correctly implementing complicated NUMA-aware locks is very difficult. We propose a Compositional Lock Framework (CLoF) for multi-level NUMA systems. CLoF composes NUMA-oblivious locks in a hierarchy matching the target platform, leading to hundreds of correct by construction NUMA-aware locks. CLoF can automatically select the best lock among them. To show the correctness of CLoF on WMMs, we provide an inductive argument with base and induction steps verified with model checkers. In our evaluation, CLoF locks outperform state-of-the-art NUMA-aware locks in most scenarios, e.g., in a highly contended LevelDB benchmark, our best CLoF locks yield twice the throughput achieved with CNA lock and ShflLock on large x86 and Armv8 servers.
Yanqi Zhang, Íñigo Goiri, Gohar Irfan Chaudhry, Rodrigo Fonseca, Sameh Elnikety, Christina Delimitrou, Ricardo Bianchini
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483580

Abstract:
Serverless computing is becoming increasingly popular due to its ease of programming, fast elasticity, and fine-grained billing. However, the serverless provider still needs to provision, manage, and pay the IaaS provider for the virtual machines (VMs) hosting its platform. This ties the cost of the serverless platform to the cost of the underlying VMs. One way to significantly reduce cost is to use spare resources, which cloud providers rent at a massive discount. Harvest VMs offer such cheap resources: they grow and shrink to harvest all the unallocated CPU cores in their host servers, but may be evicted to make room for more expensive VMs. Thus, using Harvest VMs to run the serverless platform comes with two main challenges that must be carefully managed: VM evictions and dynamically varying resources in each VM. In this work, we explore the challenges and benefits of hosting serverless (Function as a Service or simply FaaS) platforms on Harvest VMs. We characterize the serverless workloads and Harvest VMs of Microsoft Azure, and design a serverless load balancer that is aware of evictions and resource variations in Harvest VMs. We modify OpenWhisk, a widely-used open-source serverless platform, to monitor harvested resources and balance the load accordingly, and evaluate it experimentally. Our results show that adopting harvested resources improves efficiency and reduces cost. Under the same cost budget, running serverless platforms on harvested resources achieves 2.2x to 9.0x higher throughput compared to using dedicated resources. When using the same amount of resources, running serverless platforms on harvested resources achieves 48% to 89% cost savings with lower latency due to better load balancing.
Jeffrey Helt, Matthew Burke, Amit Levy, Wyatt Lloyd
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483566

Abstract:
Strictly serializable (linearizable) services appear to execute transactions (operations) sequentially, in an order consistent with real time. This restricts a transaction's (operation's) possible return values and in turn, simplifies application programming. In exchange, strictly serializable (linearizable) services perform worse than those with weaker consistency. But switching to such services can break applications. This work introduces two new consistency models to ease this trade-off: regular sequential serializability (RSS) and regular sequential consistency (RSC). They are just as strong for applications: we prove any application invariant that holds when using a strictly serializable (linearizable) service also holds when using an RSS (RSC) service. Yet they relax the constraints on services---they allow new, better-performing designs. To demonstrate this, we design, implement, and evaluate variants of two systems, Spanner and Gryff, relaxing their consistency to RSS and RSC, respectively. The new variants achieve better read-only transaction and read tail latency than their counterparts.
Kostis Kaffes, Jack Tigar Humphries, David Mazières, Christos Kozyrakis
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483548

Abstract:
Suboptimal scheduling decisions in operating systems, networking stacks, and application runtimes are often responsible for poor application performance, including higher latency and lower throughput. These poor decisions stem from a lack of insight into the applications and requests the scheduler is handling and a lack of coherence and coordination between the various layers of the stack, including NICs, kernels, and applications. We propose Syrup, a framework for user-defined scheduling. Syrup enables untrusted application developers to express application-specific scheduling policies across these system layers without being burdened with the low-level system mechanisms that implement them. Application developers write a scheduling policy with Syrup as a set of matching functions between inputs (threads, network packets, network connections) and executors (cores, network sockets, NIC queues) and then deploy it across system layers without modifying their code. Syrup supports multi-tenancy as multiple co-located applications can each safely and securely specify a custom policy. We present several examples of uses of Syrup to define application and workload-specific scheduling policies in a few lines of code, deploy them across the stack, and improve performance up to 8x compared with default policies.
Emma Dauterman, Vivian Fang, Ioannis Demertzis, Natacha Crooks, Raluca Ada Popa
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483562

Abstract:
Existing oblivious storage systems provide strong security by hiding access patterns, but do not scale to sustain high throughput as they rely on a central point of coordination. To overcome this scalability bottleneck, we present Snoopy, an object store that is both oblivious and scalable such that adding more machines increases system throughput. Snoopy contributes techniques tailored to the high-throughput regime to securely distribute and efficiently parallelize every system component without prohibitive coordination costs. These techniques enable Snoopy to scale similarly to a plaintext storage system. Snoopy achieves 13.7x higher throughput than Obladi, a state-of-the-art oblivious storage system. Specifically, Obladi reaches a throughput of 6.7K requests/s for two million 160-byte objects and cannot scale beyond a proxy and server machine. For the same data size, Snoopy uses 18 machines to scale to 92K requests/s with average latency under 500ms.
Ishtiyaque Ahmad, Laboni Sarker, Divyakant Agrawal, Amr El Abbadi, Trinabh Gupta
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483586

Abstract:
Given a private string q and a remote server that holds a set of public documents D, how can one of the K most relevant documents to q in D be selected and viewed without anyone (not even the server) learning anything about q or the document? This is the oblivious document ranking and retrieval problem. In this paper, we describe Coeus, a system that solves this problem. At a high level, Coeus composes two cryptographic primitives: secure matrix-vector product for scoring document relevance using the widely-used term frequency-inverse document frequency (tf-idf) method, and private information retrieval (PIR) for obliviously retrieving documents. However, Coeus reduces the time to run these protocols, thereby improving the user-perceived latency, which is a key performance metric. Coeus first reduces the PIR overhead by separating out private metadata retrieval from document retrieval, and it then scales secure matrix-vector product to tf-idf matrices with several hundred billion elements through a series of novel cryptographic refinements. For a corpus of English Wikipedia containing 5 million documents, a keyword dictionary with 64K keywords, and on a cluster of 143 machines on AWS, Coeus enables a user to obliviously rank and retrieve a document in 3.9 seconds---a 24x improvement over a baseline system.
Yingdi Shan, Kang Chen, Tuoyu Gong, Lidong Zhou, Tai Zhou, Yongwei Wu
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483558

Abstract:
Erasure coding is widely used in building reliable distributed object storage systems despite its high repair cost. Regenerating codes are a special class of erasure codes, which are proposed to minimize the amount of data needed for repair. In this paper, we assess how optimal repair can help to improve object storage systems, and we find that regenerating codes present unique challenges: regenerating codes repair at the granularity of chunks instead of bytes, and the choice of chunk size leads to the tension between streamed degraded read time and repair throughput. To address this dilemma, we propose Geometric Partitioning, which partitions each object into a series of chunks with their sizes in a geometric sequence to obtain the benefits of both large and small chunk sizes. Geometric Partitioning helps regenerating codes to achieve 1.85x recovery performance of RS code while keeping degraded read time low.
Wook-Hee Kim, R. Madhava Krishnan, Xinwei Fu, Sanidhya Kashyap, Changwoo Min
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483589

Abstract:
Non-Volatile Memory (NVM), which provides relatively fast and byte-addressable persistence, is now commercially available. However, we cannot equate a real NVM with a slow DRAM, as it is much more complicated than we expect. In this work, we revisit and analyze both NVM and NVM-specific persistent memory indexes. We find that there is still a lot of room for improvement if we consider NVM hardware, its software stack, persistent index design, and concurrency control. Based on our analysis, we propose Packed Asynchronous Concurrency (PAC) guidelines for designing high-performance persistent index structures. The key idea behind the guidelines is to 1) access NVM hardware in a packed manner to minimize its bandwidth utilization and 2) exploit asynchronous concurrency control to decouple the long NVM latency from the critical path of the index. We develop PACTree, a high-performance persistent range index following the PAC guidelines. PACTree is a hybrid index that employs a trie index for its internal nodes and B+-tree-like leaf nodes. The trie index structure packs partial keys in internal nodes. Moreover, we decouple the trie index and B+-tree-like leaf nodes. The decoupling allows us to prevent blocking concurrent accesses by updating internal nodes asynchronously. Our evaluation shows that PACTree outperforms state-of-the-art persistent range indexes by 7x in performance and 20x in 99.99 percentile tail latency.
Sara McAllister, Benjamin Berg, Julian Tutuncu-Macias, Juncheng Yang, Sathya Gunasekar, Jimmy Lu, Daniel S. Berger, Nathan Beckmann, Gregory R. Ganger
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483568

Abstract:
Many social-media and IoT services have very large working sets consisting of billions of tiny (≈100 B) objects. Large, flash-based caches are important to serving these working sets at acceptable monetary cost. However, caching tiny objects on flash is challenging for two reasons: (i) SSDs can read/write data only in multi-KB "pages" that are much larger than a single object, stressing the limited number of times flash can be written; and (ii) very few bits per cached object can be kept in DRAM without losing flash's cost advantage. Unfortunately, existing flash-cache designs fall short of addressing these challenges: write-optimized designs require too much DRAM, and DRAM-optimized designs require too many flash writes. We present Kangaroo, a new flash-cache design that optimizes both DRAM usage and flash writes to maximize cache performance while minimizing cost. Kangaroo combines a large, set-associative cache with a small, log-structured cache. The set-associative cache requires minimal DRAM, while the log-structured cache minimizes Kangaroo's flash writes. Experiments using traces from Facebook and Twitter show that Kangaroo achieves DRAM usage close to the best prior DRAM-optimized design, flash writes close to the best prior write-optimized design, and miss ratios better than both. Kangaroo's design is Pareto-optimal across a range of allowed write rates, DRAM sizes, and flash sizes, reducing misses by 29% over the state of the art. These results are corroborated with a test deployment of Kangaroo in a production flash cache at Facebook.
Amanda Raybuck, Tim Stamler, Wei Zhang, Mattan Erez, Simon Peter
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483550

Abstract:
High-capacity non-volatile memory (NVM) is a new main memory tier. Tiered DRAM+NVM servers increase total memory capacity by up to 8x, but can diminish memory bandwidth by up to 7x and inflate latency by up to 63% if not managed well. We study existing hardware and software tiered memory management systems on the recently available Intel Optane DC NVM with big data applications and find that no existing system maximizes application performance on real NVM. Based on our findings, we present HeMem, a tiered main memory management system designed from scratch for commercially available NVM and the big data applications that use it. HeMem manages tiered memory asynchronously, batching and amortizing memory access tracking, migration, and associated TLB synchronization overheads. HeMem monitors application memory use by sampling memory access via CPU events, rather than page tables. This allows HeMem to scale to terabytes of memory, keeping small and ephemeral data structures in fast memory, and allocating scarce, asymmetric NVM bandwidth according to access patterns. Finally, HeMem is flexible by placing per-application memory management policy at user-level. On a system with Intel Optane DC NVM, HeMem outperforms hardware, OS, and PL-based tiered memory management, providing up to 50% runtime reduction for the GAP graph processing benchmark, 13% higher throughput for TPC-C on the Silo in-memory database, 16% lower tail-latency under performance isolation for a key-value store, and up to 10x less NVM wear than the next best solution, without application modification.
Anatole Lefort, Yohan Pipereau, Kwabena Amponsem, Pierre Sutra, Gaël Thomas
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483579

Abstract:
This paper presents J-NVM, a framework to access efficiently Non-Volatile Main Memory (NVMM) in Java. J-NVM offers a fully-fledged interface to persist plain Java objects using failure-atomic blocks. This interface relies internally on proxy objects that intermediate direct off-heap access to NVMM. The framework also provides a library of highly-optimized persistent data types that resist reboots and power failures. We evaluate J-NVM by implementing a persistent backend for the Infinispan data store. Our experimental results, obtained with a TPC-B like benchmark and YCSB, show that J-NVM is consistently faster than other approaches at accessing NVMM in Java.
Aishwarya Ganesan, Ramnatthan Alagappan, Andrea C. Arpaci-Dusseau, Remzi H. Arpaci-Dusseau
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483543

Abstract:
Do some storage interfaces enable higher performance than others? Can one identify and exploit such interfaces to realize high performance in storage systems? This paper answers these questions in the affirmative by identifying nil-externality, a property of storage interfaces. A nil-externalizing (nilext) interface may modify state within a storage system but does not externalize its effects or system state immediately to the outside world. As a result, a storage system can apply nilext operations lazily, improving performance. In this paper, we take advantage of nilext interfaces to build high-performance replicated storage. We implement Skyros, a nilext-aware replication protocol that offers high performance by deferring ordering and executing operations until their effects are externalized. We show that exploiting nil-externality offers significant benefit: for many workloads, Skyros provides higher performance than standard consensus-based replication. For example, Skyros offers 3x lower latency while providing the same high throughput offered by throughput-optimized Paxos.
Adar Zeitak, Adam Morrison
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483551

Abstract:
We present the Cuckoo Trie, a fast, memory-efficient ordered index structure. The Cuckoo Trie is designed to have memory-level parallelism---which a modern out-of-order processor can exploit to execute DRAM accesses in parallel--- without sacrificing memory efficiency. The Cuckoo Trie thus breaks a fundamental performance barrier faced by current indexes, whose bottleneck is a series of dependent pointer-chasing DRAM accesses---e.g., traversing a search tree path--- which the processor cannot parallelize. Our evaluation shows that the Cuckoo Trie outperforms state-of-the-art-indexes by up to 20%-360% on a variety of datasets and workloads, typically with a smaller or comparable memory footprint.
Xiaojian Liao, Youyou Lu, Zhe Yang, Jiwu Shu
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483592

Abstract:
This paper presents crash consistent Non-Volatile Memory Express (ccNVMe), a novel extension of the NVMe that defines how host software communicates with the non-volatile memory (e.g., solid-state drive) across a PCI Express bus with both crash consistency and performance efficiency. Existing storage systems pay a huge tax on crash consistency, and thus can not fully exploit the multi-queue parallelism and low latency of the NVMe interface. ccNVMe alleviates this major bottleneck by coupling the crash consistency to the data dissemination. This new idea allows the storage system to achieve crash consistency by taking the free rides of the data dissemination mechanism of NVMe, using only two lightweight memory-mapped I/Os (MMIO), unlike traditional systems that use complex update protocol and heavyweight block I/Os. ccNVMe introduces transaction-aware MMIO and doorbell to reduce the PCIe traffic as well as to provide atomicity. We present how to build a high-performance and crash-consistent file system namely MQFS atop ccNVMe. We experimentally show that MQFS increases the IOPS of RocksDB by 36% and 28% compared to a state-of-the-art file system and Ext4 without journaling, respectively.
Hao Sun, Yuheng Shen, Cong Wang, Jianzhong Liu, Yu Jiang, Ting Chen, Aiguo Cui
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483547

Abstract:
Modern operating system kernels are too complex to be free of bugs. Fuzzing is a promising approach for vulnerability detection and has been applied to kernel testing. However, existing work does not consider the influence relations between system calls when generating and mutating inputs, resulting in difficulties when trying to reach into the kernel's deeper logic effectively. In this paper, we propose HEALER, a kernel fuzzer that improves fuzzing's effectiveness by utilizing system call relation learning. HEALER learns the influence relations between system calls by dynamically analyzing minimized test cases. Then, HEALER utilizes the learned relations to guide input generation and mutation, which improves the quality of test cases and the effectiveness of fuzzing. We implemented HEALER and evaluated its performance on recent versions of the Linux kernel. Compared to state-of-the-art kernel fuzzers such as Syzkaller and Moonshine, HEALER improves branch coverage by 28% and 21%, while achieving a speedup of 2.2x and 1.8x, respectively. In addition, HEALER detected 218 vulnerabilities, 33 of which are previously unknown and have been confirmed by the corresponding kernel maintainers.
Jongyul Kim, Insu Jang, Waleed Reda, Jaeseong Im, Marco Canini, Dejan Kostić, Youngjin Kwon, Simon Peter, Emmett Witchel
Proceedings of the ACM SIGOPS 28th Symposium on Operating Systems Principles CD-ROM; https://doi.org/10.1145/3477132.3483565

Abstract:
In multi-tenant systems, the CPU overhead of distributed file systems (DFSes) is increasingly a burden to application performance. CPU and memory interference cause degraded and unstable application and storage performance, in particular for operation latency. Recent client-local DFSes for persistent memory (PM) accelerate this trend. DFS offload to SmartNICs is a promising solution to these problems, but it is challenging to fit the complex demands of a DFS onto simple SmartNIC processors located across PCIe. We present LineFS, a SmartNIC-offloaded, high-performance DFS with support for client-local PM. To fully leverage the SmartNIC architecture, we decompose DFS operations into execution stages that can be offloaded to a parallel datapath execution pipeline on the SmartNIC. LineFS offloads CPU-intensive DFS tasks, like replication, compression, data publication, index and consistency management to a Smart-NIC. We implement LineFS on the Mellanox BlueField Smart-NIC and compare it to Assise, a state-of-the-art PM DFS. LineFS improves latency in LevelDB up to 80% and throughput in Filebench up to 79%, while providing extended DFS availability during host system failures.
Redaktion Facharztmagazine
Published: 26 October 2021
gynäkologie + geburtshilfe, Volume 26, pp 63-63; https://doi.org/10.1007/s15013-021-4225-8

Martin Sebastian Greiff
Published: 26 October 2021
gynäkologie + geburtshilfe, Volume 26, pp 56-57; https://doi.org/10.1007/s15013-021-4208-9

Günter Emons
Published: 26 October 2021
gynäkologie + geburtshilfe, Volume 26, pp 35-37; https://doi.org/10.1007/s15013-021-4207-x

Christoph Keck, Sabine Segerer
Published: 26 October 2021
gynäkologie + geburtshilfe, Volume 26, pp 38-45; https://doi.org/10.1007/s15013-021-4206-y

Redaktion Facharztmagazine
Published: 26 October 2021
gynäkologie + geburtshilfe, Volume 26, pp 63-63; https://doi.org/10.1007/s15013-021-4226-7

Regina Steuder, Hendrik Pott, Michael Maxheim, Bernd Schmeck
Published: 26 October 2021
Pneumo News, Volume 13, pp 30-35; https://doi.org/10.1007/s15033-021-2749-1

Published: 26 October 2021
by MDPI
Journal of Marine Science and Engineering, Volume 9; https://doi.org/10.3390/jmse9111177

Abstract:
Climate warming has enabled the Arctic region to achieve seasonal navigation, and sea ice concentration is an important factor affecting the navigation of the Arctic waterways. This article uses the Arctic sea ice concentration data of the three highest temperatures in 2016, 2019, and 2020, combined with the Arctic summer sea level pressure, wind field, temperature, temperature anomaly, ice age, and sea ice movement data to analyze the spatial and temporal variation of sea ice and connectivity in the Northeast Passage (NEP) of the Arctic in Summer in three hot years, and summarizes the causes of sea ice anomalies. The results show that: (1) the summer Arctic sea ice extent in 2016, 2019 and 2020 were all lower than the multi-year average sea ice extent, and the summer sea ice extent in 2020 had the largest change trend; (2) in October of these three years, the sea ice was all negative anomalies, extending the opening time of the NEP; (3) when the sea ice concentration was 30% as the threshold, the navigation period of the NEP in 2016 was from mid-August to late October, 2019 was from the beginning of August to mid-October, 2020 was from the end of July to the end of October, and 2020 was the longest year since the opening of the NEP; (4) when the sea ice concentration was 10% as the threshold, the navigation period of the NEP in 2016 was from the end of August to the end of October, 2019 was from early August to mid-October, and 2020 was from the beginning of August to the end of October; (5) the key navigable areas of the NEP in the past three years were the central waters of the East Siberian Sea, the New Siberian Islands and the Vilkitsky Strait; (6) the navigation period of the NEP in 2016, 2019 and 2020 was longer. The main reasons were that the temperature of the NEP in the past 3 years was relatively high, the wind was weak, the sea ice movement had little effect, and the sea ice age in the key navigable areas was first year ice, which was easy to melt, which greatly promoted the opening of the NEP.
Published: 26 October 2021
by MDPI
Journal of Fungi, Volume 7; https://doi.org/10.3390/jof7110906

Abstract:
Ashbya gossypii is a filamentous fungus that is currently exploited for the industrial production of riboflavin. In addition, metabolically engineered strains of A. gossypii have also been described as valuable biocatalysts for the production of different metabolites such as folic acid, nucleosides, and biolipids. Hence, bioproduction in A. gossypii relies on the availability of well-performing gene expression systems both for endogenous and heterologous genes. In this regard, the identification of novel promoters, which are critical elements for gene expression, decisively helps to expand the A. gossypii molecular toolbox. In this work, we present an adaptation of the Dual Luciferase Reporter (DLR) Assay for promoter analysis in A. gossypii using integrative cassettes. We demonstrate the efficiency of the analysis through the identification of 10 new promoters with different features, including carbon source-regulatable abilities, that will highly improve the gene expression platforms used in A. gossypii. Three novel strong promoters (PCCW12, PSED1, and PTSA1) and seven medium/weak promoters (PHSP26, PAGL366C, PTMA10, PCWP1, PAFR038W, PPFS1, and PCDA2) are presented. The functionality of the promoters was further evaluated both for the overexpression and for the underexpression of the A. gossypiiMSN2 gene, which induced significant changes in the sporulation ability of the mutant strains.
Published: 26 October 2021
by MDPI
Abstract:
High-Z gold nanoparticles (AuNPs) conjugated to a targeting antibody can help to improve tumor control in radiotherapy while simultaneously minimizing radiotoxicity to adjacent healthy tissue. This paper summarizes the main findings of a joint research program which applied AuNP-conjugates in preclinical modeling of radiotherapy at the Klinikum rechts der Isar, Technical University of Munich and Helmholtz Zentrum München. A pharmacokinetic model of superparamagnetic iron oxide nanoparticles was developed in preparation for a model simulating the uptake and distribution of AuNPs in mice. Multi-scale Monte Carlo simulations were performed on a single AuNP and multiple AuNPs in tumor cells at cellular and molecular levels to determine enhancements in the radiation dose and generation of chemical radicals in close proximity to AuNPs. A biologically based mathematical model was developed to predict the biological response of AuNPs in radiation enhancement. Although simulations of a single AuNP demonstrated a clear dose enhancement, simulations relating to the generation of chemical radicals and the induction of DNA strand breaks induced by multiple AuNPs showed only a minor dose enhancement. The differences in the simulated enhancements at molecular and cellular levels indicate that further investigations are necessary to better understand the impact of the physical, chemical, and biological parameters in preclinical experimental settings prior to a translation of these AuNPs models into targeted cancer radiotherapy.
Published: 26 October 2021
by MDPI
Abstract:
Backround and Objectives: Alternative, non-invasive, and non-pharmaceutical options are gaining place in the battle of Alzheimer’s Disease treatment control. Lately, the magnetic stimulation of the brain is the most prevalent technique with encouraging results. The aim of this study is to establish any possible change on the Primary Dominant Frequencies (PDF) (range 2–7 Hz) of the affected brain regions in Alzheimer Disease (AD) patients after applying extremely weak Transcranial Magnetic Stimulation. Materials and Methods: For this purpose, all AD patients were scanned with the use of MagnetoEncephaloGraphy (MEG) recordings through a whole-head 122–channel MEG system. Results: Our results exerted statistically significant PDF changes due to weak TMS accompanied by rabid attenuation of clinical symptoms. Conclusion: Thus, this is the first time that a positive therapeutic effect is being demonstrated even at pico-Tesla range magnetic fields in a small clinical group of studies for AD.
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