Lightweight asynchronous scheduling in heterogeneous reconfigurable systems

The trend for heterogeneous embedded systems is the integration of accelerators and general-purpose CPU cores on the same die. In these integrated architectures, like the Zynq UltraScale+ board (CPU+FPGA) that we target in this work, hardware support for shared memory and low-overhead synchronization between the accelerator and the CPU cores make the case for exploring strategies that exploit a tight collaboration between the CPUs and the accelerator. In this paper we propose a novel lightweight scheduling strategy, FastFit, targeted to FPGA accelerators, and a new scheduler based on it, named MultiFastFit, which asynchronously tackles heterogeneous systems comprised of a variety of CPU cores and FPGA IPs. Our strategy significantly reduces the overhead to automatically compute the near-optimal chunksizes when compared to a previous state-of-the-art auto-tuned approach, which makes our approach more suitable for fine-grained applications. Additionally, our scheduler MultiFastFit has been designed to enable the efficient co-execution of work among compute devices in such a way that all the devices are busy while minimizing the load unbalance. Our approaches have been evaluated using four benchmarks carefully tuned for the low-power UltraScale+ platform. Our experiments demonstrate that the FastFit strategy always finds the near-optimal FPGA chunksize for any device configuration at a reasonable cost, even for fine-grained and irregular applications, and that heterogeneous CPU+FPGA co-executions that exploit all the compute devices are usually faster and more energy efficient than the CPU-only and FPGA-only executions. We have also compared MultiFastFit with other state-of-the-art scheduling strategies, finding that it outperforms other auto-tuned approach up to 2x and it achieves similar results to manually-tuned schedulers without requiring an offline search of the ideal CPU-FPGA partition or FPGA chunk granularity. © 2022 The Author

A saddle in a corner - a model of collinear triatomic chemical reactions

A geometrical model which captures the main ingredients governing atom-diatom collinear chemical reactions is proposed. This model is neither near-integrable nor hyperbolic, yet it is amenable to analysis using a combination of the recently developed tools for studying systems with steep potentials and the study of the phase space structure near a center-saddle equilibrium. The nontrivial dependence of the reaction rates on parameters, initial conditions and energy is thus qualitatively explained. Conditions under which the phase space transition state theory assumptions are satisfied and conditions under which these fail are derived

Some remarks on the geometry of the Standard Map

We define and compute hyperbolic coordinates and associated foliations which provide a new way to describe the geometry of the standard map. We also identify a uniformly hyperbolic region and a complementary 'critical' region containing a smooth curve of tangencies between certain canonical 'stable' foliations.Comment: 25 pages, 11 figure

Little-Parks effect and multiquanta vortices in a hybrid superconductor--ferromagnet system

Within the phenomenological Ginzburg-Landau theory we investigate the phase diagram of a thin superconducting film with ferromagnetic nanoparticles. We study the oscillatory dependence of the critical temperature on an external magnetic field similar to the Little-Parks effect and formation of multiquantum vortex structures. The structure of a superconducting state is studied both analytically and numerically.Comment: 7 pages, 1 figure. Submitted to J. Phys.: Condens. Mat

Genotyping of tick-borne encephalitis and Kemerovo viruses in taiga ticks collected in the Komi Republic

Over the last years, an increasing rate of ixodes tick bites has been registered in the northern regions of the European Russia. In addition, the number of subjects request medical assistance due to tick bites has been dramatically increased in the Komi Republic. In addition, incidence of tick-borne encephalitis was also increased particularly starting since 2009. However, highly limited data on pathogen genetic diversity related to viral tick-borne infections in this region are currently available. Taiga ticks (Ixodespersulcatus) collected from the Komi Republic southern and central part vegetation were examined to identify and genotype tick-borne viruses. Individual ticks were used to identify by RT-PCR viral RNA coupled to tick-borne encephalitis and Kemerovo viruses. Viral genome fragment sequencing allowed to unambiguously identify these viruses. It was found that viral RNA tick-borne encephalitis was detected in 6.8±1.2% individual ticks. Moreover, tick-linked isolate genotyping based on analyzing E protein gene fragment nucleotide sequence derived from tick-borne encephalitis discovered that 35% and 65% isolates belonged to the Far Eastern and Siberian subtype, respectively. In addition, subsequent phylogenetic analysis demonstrated that at least four variants of the Siberian and Far Eastern subtypes of tick-borne encephalitis virus were detected, which were close to the viruses circulating in the Urals and Siberia. In contrast, prevalence of Kemerovo virus in taiga ticks was 0.8±0.2%. Sequencing of Kemerovo virus RNA-dependent RNA polymerase gene fragment showed around 94% homology with the remainder of the Kemerovo virus strains. Phylogenetic analysis of the Kemerovo virus genome fragments demonstrated at least two subtypes circulating in the Komi Republic. Thus, it was suggested that tick-borne encephalitis virus was introduced relatively recently from the Urals and Siberian region into the natural foci of the Komi Republic. Moreover, genetic differences found in Kemerovo virus strains presume for them a longer lasting evolution throughout the natural foci of this region. In addition, a potential role for birds and their ticks in rapid spreading of viral tick-borne infections in the Komi Republic is also discussed. Thus, the data on genetic diversity of the viral agents related to tick-born encephalitis and Kemerovo fever may be useful for improving their diagnostics, prevention and treatment in the Komi Republic

ЭКЗОСОМЫ И ПЕРЕДАЧА (ЭПИ)ГЕНЕТИЧЕСКОЙ ИНФОРМАЦИИ ОПУХОЛЕВЫМИ КЛЕТКАМИ

In this review, we will introduce the current knowledge about exosomes – vesicles that are generated in the cells and released into the extracellular space. Exosomes are forming in the cell plasma membrane and represent the spherical shapes restricted by their membrane and contained the various biomolecules including nucleic acids, proteins, lipids etc. The intent interest to exosomes is based on their ability to horizontal transfer between the cells, to permeate into vascular system reaching the different tissues and to incorporate into the recipient cells. It was shown that exosome incorporation into the cells lead to remarkable changes in the recipient cells both in genomic level (via the integration of exosomal DNA into the host DNA) and in epigenomic level (via the modulation of the content and/or activity of the signaling proteins, microRNA etc.). Undoubtedly, one of the most interesting and perspective achievements in the exosome study is the demonstration of exosome ability to provide the horizontal transfer of the genetic information from cell to cell – the fact supported in the different studies with the various cell models. Here, we will discuss the recent data regarding the main characteristics and properties of exosomes, the role of exosomes in the tumorigenesis including neoplastic transformation, metastasis, multi-drug resistance. The final part of the review involves the most growing area in the exosome study – the possible usage of exosomes in the cancer treatment, in particular – as the specific drug delivery system.В обзоре рассматриваются современные представления об экзосомах – везикулах, образующихся внутри клеток и секретируемых в окружающую среду. Они формируются на плазматической мембране клеток и представляют собой сферические структуры, ограниченные своей мембраной и содержащие различные биомолекулы, включая нуклеиновые кислоты, белки, липиды и проч. Обнаруженные в последние годы свойства экзосом перемещаться между клетками, проходить в кровяное русло, достигая самых различных тканей, и в итоге проникать внутрь клеток-реципиентов обеспечили пристальное внимание исследователей к изучению их биологических функций. Установлено, что экзосомы, проникая в клетки-реципиенты, могут вызывать в них целый каскад изменений на геномном (за счет интеграции ДНК) и эпигеномном (за счет изменения экспрессии/содержания белков, микроРНК и проч.) уровнях. Безусловно, одним из самых интересных и значимых достижений в изучении экзосом явилось установление возможности горизонтальной передачи информации от клетки к клетке с их участием – факт, неоднократно продемонстрированный исследователями на разных моделях. В обзоре приводятся современные данные об основных характеристиках и свойствах экзосом; о роли экзосом в развитии злокачественных новообразований, в частности – об их участии в опухолевой трансформации, метастазировании, формировании лекарственной устойчивости. Заключительный раздел обзора посвящен одному из наиболее стремительно развивающихся направлений в этой области – использованию экзосом в клинической практике, в том числе для избирательной доставки противоопухолевых препаратов в опухоль

Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells

<p>Abstract</p> <p>Background</p> <p>Zearalenone (ZEA) is a phytoestrogen from <it>Fusarium </it>species. The aims of the study was to identify mode of human leukemic cell death induced by ZEA and the mechanisms involved.</p> <p>Methods</p> <p>Cell cytotoxicity of ZEA on human leukemic HL-60, U937 and peripheral blood mononuclear cells (PBMCs) was performed by using 3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Reactive oxygen species production, cell cycle analysis and mitochondrial transmembrane potential reduction was determined by employing 2',7'-dichlorofluorescein diacetate, propidium iodide and 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, respectively. Caspase-3 and -8 activities were detected by using fluorogenic Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC) and Ile-Glu-Thr-Asp-7-amino-4-methylcoumarin (IETD-AMC) substrates, respectively. Protein expression of cytochrome c, Bax, Bcl-2 and Bcl-xL was performed by Western blot. The expression of proteins was assessed by two-dimensional polyacrylamide gel-electrophoresis (PAGE) coupled with LC-MS2 analysis and real-time reverse transcription polymerase chain reaction (RT-PCR) approach.</p> <p>Results</p> <p>ZEA was cytotoxic to U937 > HL-60 > PBMCs and caused subdiploid peaks and G1 arrest in both cell lines. Apoptosis of human leukemic HL-60 and U937 cell apoptosis induced by ZEA was via an activation of mitochondrial release of cytochrome c through mitochondrial transmembrane potential reduction, activation of caspase-3 and -8, production of reactive oxygen species and induction of endoplasmic reticulum stress. Bax was up regulated in a time-dependent manner and there was down regulation of Bcl-xL expression. Two-dimensional PAGE coupled with LC-MS2 analysis showed that ZEA treatment of HL-60 cells produced differences in the levels of 22 membrane proteins such as apoptosis inducing factor and the ER stress proteins including endoplasmic reticulum protein 29 (ERp29), 78 kDa glucose-regulated protein, heat shock protein 90 and calreticulin, whereas only <it>ERp29 </it>mRNA transcript increased.</p> <p>Conclusion</p> <p>ZEA induced human leukemic cell apoptosis via endoplasmic stress and mitochondrial pathway.</p

Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

Pancreatic Adenocarcinoma (PDAC), the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS) and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX). A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7) and Alpha Synuclein (aSyn), both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP) which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC

Active fixturing: literature review and future research directions

Fixtures are used to fixate, position and support workpieces and represent a crucial tool in manufacturing. Their performance determines the result of the whole manufacturing process of a product. There is a vast amount of research done on automatic fixture layout synthesis and optimisation and fixture design verification. Most of this work considers fixture mechanics to be static and the fixture elements to be passive. However, a new generation of fixtures has emerged that has actuated fixture elements for active control of the part–fixture system during manufacturing operations to increase the end product quality. This paper analyses the latest studies in the field of active fixture design and its relationship with flexible and reconfigurable fixturing systems. First, a brief introduction is given on the importance of research of fixturing systems. Secondly, the basics of workholding and fixture design are visited, after which the state-of-the-art in active fixturing and related concepts is presented. Fourthly, part–fixture dynamics and design strategies which take these into account are discussed. Fifthly, the control strategies used in active fixturing systems are examined. Finally, some final conclusions and prospective future research directions are presented

Oxidative protein labeling in mass-spectrometry-based proteomics

Oxidation of proteins and peptides is a common phenomenon, and can be employed as a labeling technique for mass-spectrometry-based proteomics. Nonspecific oxidative labeling methods can modify almost any amino acid residue in a protein or only surface-exposed regions. Specific agents may label reactive functional groups in amino acids, primarily cysteine, methionine, tyrosine, and tryptophan. Nonspecific radical intermediates (reactive oxygen, nitrogen, or halogen species) can be produced by chemical, photochemical, electrochemical, or enzymatic methods. More targeted oxidation can be achieved by chemical reagents but also by direct electrochemical oxidation, which opens the way to instrumental labeling methods. Oxidative labeling of amino acids in the context of liquid chromatography(LC)–mass spectrometry (MS) based proteomics allows for differential LC separation, improved MS ionization, and label-specific fragmentation and detection. Oxidation of proteins can create new reactive groups which are useful for secondary, more conventional derivatization reactions with, e.g., fluorescent labels. This review summarizes reactions of oxidizing agents with peptides and proteins, the corresponding methodologies and instrumentation, and the major, innovative applications of oxidative protein labeling described in selected literature from the last decade