Parallel Fragments Research Articles

Alterations in Coronary Resistance Artery Network Geometry in Diabetes and the Role of Tenascin C.

Geometrical alterations in the coronary resistance artery network and the potential involvement of Tenascin C (TNC) extracellular matrix protein were investigated in diabetic and control mice. Diabetes was induced by streptozotocin (STZ) injections (n = 7-11 animals in each group) in Tenascin C KO (TNC KO) mice and their Wild type (A/J) littermates. After 16-18 weeks the heart was removed and the whole subsurface network of the left coronary artery was prepared (down to branches of 40 m outer diameter), in situ pressure-perfused and studied using video-microscopy. Outer and inner diameters, wall thicknesses and bifurcation angles were measured on whole network pictures reconstructed into collages at 1.7 m pixel resolutions. Diabetes induced abnormal morphological alterations including trifurcations, sharp bends of larger branches, and branches directed retrogradely (p 0.001 by the 2 test). Networks of TNC KO mice tended to form early divisions producing parallelly running larger branches (p 0.001 by the 2 probe). Networks of coronary resistance arteries were substantially more abundant in 100-180 m components, appearing in 2-5 mm flow distance from orifice in diabetes. This was accompanied by thickening of the wall of larger arterioles ( 220 m) and thinning of the wall of smaller (100-140 m) arterioles (p 0.001). Blood flow should cover larger distances in diabetic networks, but interestingly STZ-induced diabetes did not generate further geometrical changes in TNC KO mice. Diabetes promotes hypertrophic and hypotrophic vascular remodeling and induces vasculogenesis at well defined, specific positions of the coronary vasculature. TNC plays a pivotal role in the formation of coronary network geometry, and TNC deletion causes parallel fragmentation preventing diabetes-induced abnormal vascular morphologies.

Proteomic and phosphoproteomic landscape of salivary extracellular vesicles to assess OSCC therapeutical outcomes.

Circulating extracellular vesicles (EVs) have emerged as an appealing source for surrogates to evaluate the disease status. Herein, we present a novel proteomic strategy to identify proteins and phosphoproteins from salivary EVs to distinguish oral squamous cell carcinoma (OSCC) patients from healthy individuals and explore the feasibility to evaluate therapeutical outcomes. Bi-functionalized magnetic beads (BiMBs) with Ti (IV) ions and a lipid analog, 1,2-Distearoyl-3-sn-glycerophosphoethanolamine (DSPE) are developed to efficiently isolate EVs from small volume of saliva. In the discovery stage, label-free proteomics and phosphoproteomics quantification showed 315 upregulated proteins and 132 upregulated phosphoproteins in OSCC patients among more than 2500 EV proteins and 1000 EV phosphoproteins, respectively. We further applied targeted proteomics by coupling parallel reaction monitoring with parallel accumulation-serial fragmentation (prm-PASEF) to measure panels of proteins and phosphoproteins from salivary EVs collected before and after surgical resection. A panel of three total proteins and three phosphoproteins, most of which have previously been associated with OSCC and other cancer types, show sensitive response to the therapy in individual patients. Our study presents a novel strategy to the discovery of effective biomarkers for non-invasive assessment of OSCC surgical outcomes with small amount of saliva.

Optimizing single cell proteomics using trapped ion mobility spectrometry for label-free experiments.

Although single cell RNA-seq has had a tremendous impact on biological research, a corresponding technology for unbiased mass spectrometric analysis of single cells has only recently become available. Significant technological breakthroughs including miniaturized sample handling have enabled proteome profiling of single cells. Furthermore, trapped ion mobility spectrometry (TIMS) in combination with parallel accumulation-serial fragmentation operated in data-dependent acquisition mode (DDA-PASEF) allowed improved proteome coverage from low-input samples. It has been demonstrated that modulating the ion flux in TIMS affects the overall performance of proteome profiling. However, the effect of TIMS settings on the analysis of low-input samples has been less investigated. Thus, we sought to optimize the conditions of TIMS with regard to ion accumulation/ramp times and ion mobility range for low-input samples. We observed that an ion accumulation time of 180 ms and monitoring a narrower ion mobility range from 0.7 to 1.3 V s cm-2 resulted in a substantial gain in the depth of proteome coverage and in detecting proteins with low abundance. We used these optimized conditions for proteome profiling of sorted human primary T cells, which yielded an average of 365, 804, 1116, and 1651 proteins from single, five, ten, and forty T cells, respectively. Notably, we demonstrated that the depth of proteome coverage from a low number of cells was sufficient to delineate several essential metabolic pathways and the T cell receptor signaling pathway. Finally, we showed the feasibility of detecting post-translational modifications including phosphorylation and acetylation from single cells. We believe that such an approach could be applied to label-free analysis of single cells obtained from clinically relevant samples.

Новый поэтический перевод и анализ изобразительно-выразительных средств, использованных в стихотворении Ду Фу «Отправляюсь из Ланчжуна»

The aim of this study is to complete a new literary translation of Du Fu’s poem “I’m Leaving Langzhong”. The scientific novelty of the study is due to the fact that literary translation is a transformation of prose translation, and the latter, in turn, is based on the analysis of all the lines of the poem in terms of immediate constituents and the study of the figurative and expressive means of the original work. The immediate constituents analysis also allows us to classify parallel fragments of the poem in question according to direction. As a result, the proposed poetic translation, on the one hand, quite accurately conveys the meaning of the original poem, and on the other hand, meets the requirements and expectations of the widest range of the Russian-speaking readers. In addition, the analysis of the figurative and expressive means used by Du Fu is carried out. It is proved that the poem contains parallel fragments characterized by both vertical and horizontal symmetry. Parallelism is complemented by rhetorical questions, antitheses and hyperboles. The performed analysis of the means of artistic expression will allow more fully preserving the figurativeness of the original work in the translation text.

Структурная классификация параллельных фрагментов стихотворения Ду Фу «Оплакиваю поражение при Чэньтао»

The aim of the study is to provide a structural classification of parallel fragments of Du Fu’s poem “Lament on the Defeat at Chen Tao”. Scientific novelty of the study lies in the fact that a parallelism analysis of this poem based on an immediate constituents analysis of its lines has not been carried out before. As a result of the study, it has been shown that the work under consideration contains parallel fragments characterised by vertical and horizontal symmetry. These types of symmetry complement each other without any predominance of one over the other. Two fragments parallel in the horizontal direction have global symmetry, whereas all fragments characterised by vertical symmetry are local, being on one side of the caesura. Parallel fragments make up 69.6% of the total number of characters in the poem. As for figurative and expressive means, parallelism dominates, being complemented by four epithets.

GeNVoM: Read Mapping Near Non-Volatile Memory.

DNA sequencing is the physical/biochemical process of identifying the location of the four bases (Adenine, Guanine, Cytosine, Thymine) in a DNA strand. As semiconductor technology revolutionized computing, modern DNA sequencing technology (termed Next Generation Sequencing, NGS) revolutionized genomic research. As a result, modern NGS platforms can sequence hundreds of millions of short DNA fragments in parallel. The sequenced DNA fragments, representing the output of NGS platforms, are termed reads. Besides genomic variations, NGS imperfections induce noise in reads. Mapping each read to (the most similar portion of) a reference genome of the same species, i.e., read mapping, is a common critical first step in a diverse set of emerging bioinformatics applications. Mapping represents a search-heavy memory-intensive similarity matching problem, therefore, can greatly benefit from near-memory processing. Intuition suggests using fast associative search enabled by Ternary Content Addressable Memory (TCAM) by construction. However, the excessive energy consumption and lack of support for similarity matching (under NGS and genomic variation induced noise) renders direct application of TCAM infeasible, irrespective of volatility, where only non-volatile TCAM can accommodate the large memory footprint in an area-efficient way. This paper introduces GeNVoM, a scalable, energy-efficient and high-throughput solution. Instead of optimizing an algorithm developed for general-purpose computers or GPUs, GeNVoM rethinks the algorithm and non-volatile TCAM-based accelerator design together from the ground up. Thereby GeNVoM can improve the throughput by up to 3.67×; the energy consumption, by up to 1.36×, when compared to an ASIC baseline, which represents one of the highest-throughput implementations known.

Средства художественной выразительности в стихотворении Бо Цзюйи «Чувства, вызванные созерцанием луны»

The study aims to determine the percentage of parallel fragments in Bai Juyi’s poem “Feelings on Watching the Moon” out of the total number of characters. For this purpose, the researcher will consider fragments characterised by both local and global parallelism as parallel fragments. The study is novel in that it is the first in Russian academic literature to carry out such an analysis of the parallelism of this work that is based on analysing all the lines of the poem at the level of phrases. As a result of the study, it has been shown that the poem under consideration is characterised by vertical and horizontal, local and global symmetry, with horizontal and vertical symmetry complementing each other. None of these types of symmetry is dominant. Parallel fragments make up 87.5% of the total number of characters in the poem. Parallelism is complemented by four metaphors, one symbol and expressive-emotive vocabulary.

Enhancement of Proteome Coverage by Ion Mobility Fractionation Coupled to PASEF on a TIMS-QTOF Instrument.

Trapped ion-mobility spectrometry (TIMS) was used to fractionate ions in the gas phase based on their ion mobility (V s/cm2), followed by parallel accumulation-serial fragmentation (PASEF) using a quadrupole time-of-flight instrument to determine the effect on the depth of proteome coverage. TIMS fractionation (up to four gas-phase fractions) coupled to data-dependent acquisition (DDA)-PASEF resulted in the detection of ∼7000 proteins and over 70,000 peptides overall from 200 ng of human (HeLa) cell lysate per injection using a commercial 25 cm ultra high performance liquid chromatography (UHPLC) column with a 90 min gradient. This result corresponded to ∼19 and 30% increases in protein and peptide identifications, respectively, when compared to a default, single-range TIMS DDA-PASEF analysis. Quantitation precision was not affected by TIMS fractionation as demonstrated by the average and median coefficient of variation values that were less than 4% upon label-free quantitation of technical replicates. TIMS fractionation was utilized to generate a DDA-based spectral library for downstream data-independent acquisition (DIA) analysis of lower sample input using a shorter LC gradient. The TIMS-fractionated library, consisting of over 7600 proteins and 82,000 peptides, enabled the identification of ∼4000 and 6600 proteins from 10 and 200 ng of human (HeLa) cell lysate input, respectively, with a 20 min gradient, single-shot DIA analysis. Data are available in ProteomeXchange: identifier PXD033129.

Классификация параллелизма танских четверостиший, содержащих пять слогов в строке, по направлению

The study aims to develop a classification of syntactic parallelism of Tang quatrains containing five syllables in a line according to the direction of parallel fragments. Syntactic parallelism of such works can be: 1) partially vertical; 2) completely vertical; 3) horizontal; 4) both vertical and horizontal; 5) zero. The study is novel in that it applies an old method (immediate constituents analysis) to new material, i.e. selected Tang quatrains containing five characters in each line. As a result of the study, the researcher is able to classify any Tang poems by the percentage of parallel fragments of the total number of characters in the poem.

Advances in data-independent acquisition mass spectrometry towards comprehensive digital proteome landscape.

The data-independent acquisition mass spectrometry (DIA-MS) has rapidly evolved as a powerful alternative for highly reproducible proteome profiling with a unique strength of generating permanent digital maps for retrospective analysis of biological systems. Recent advancements in data analysis software tools for the complex DIA-MS/MS spectra coupled to fast MS scanning speed and high mass accuracy have greatly expanded the sensitivity and coverage of DIA-based proteomics profiling. Here, we review the evolution of the DIA-MS techniques, from earlier proof-of-principle of parallel fragmentation of all-ions or ions in selected m/z range, the sequential window acquisition of all theoretical mass spectra (SWATH-MS) to latest innovations, recent development in computation algorithms for data informatics, and auxiliary tools and advanced instrumentation to enhance the performance of DIA-MS. We further summarize recent applications of DIA-MS and experimentally-derived as well as in silico spectra library resources for large-scale profiling to facilitate biomarker discovery and drug development in human diseases with emphasis on the proteomic profiling coverage. Toward next-generation DIA-MS for clinical proteomics, we outline the challenges in processing multi-dimensional DIA data set and large-scale clinical proteomics, and continuing need in higher profiling coverage and sensitivity.

Ресурсонезависимое описание информационных графов с дистрибутивными операциями на языке программирования Set@l

In the paper, we suggest to transform a standard sequential topology of an information graph with distributive operations into its hybrid version with sequential and parallel fragments. Such transformation allows to provide efficient description of calculations in the resource-independent form. The result topology depends on available hardware resource of a reconfigurable system and provides an increase in the special performance in comparison to the initial topology. We have developed an algorithm of a linear structure transformation into various hybrid topologies according to the configuration of the computing system. The algorithm is described in the Set@l programming language.

Мессианские фрагменты книги пророка Амоса LXX в их эсхатологическом контексте

In the book of the prophet Amos of the Septuagint there are two explicitly Messianic fragments, the first of which mentions the «anointed one» (Am 4:13), and the second «tabernacle of David» along with eschatological events associated with it (Am 9:11-12). However, other ancient versions of the Bible do not support the Septuagint (except for those dependent on it), which leads many researchers to look at the old Greek reading in Am 4:13 as a simple mistake of the translator or his misinterpretation of the original meaning of the text. At the same time, it cannot be said that in terms of interpretation, Masoretic reading provides more for understanding the book as a whole than that presented in the Septuagint. On the contrary, the use of structural analysis, which allows us to explore Am 4:13 by LXX in the context of parallel places within the book and its general eschatological storyline, creates a more coherent and clear picture associated with the archetypical confrontation of the «house of Jeroboam» and the «house of David» as embodiments of the sinful and righteous sides of Israel. The revelation of the «anointed one» in this regard turns out to be what heralds the end of the «house of Jeroboam» and opens up the prospect of judgment on Israel, but also its salvation in an eschatological perspective. The article consists of four main parts. The first of them examines the features of the Book of the Prophet Amos according to the Septuagint version as a translation, which allow us to draw preliminary conclusions about what may be the probable causes of discrepancies between the Hebrew and Greek texts. In the second part, the two Messianic fragments are analyzed mainly by their lexical composition, an analysis of specific discrepancies is carried out and ways of their interpretation are outlined. The third part is devoted to the explication of the eschatological line of the book. The fourth part establishes the place of the Messianic fragments and the parallel fragment Am 7:1-9 in the context of the eschatological content of this prophetic book as a whole.

Caging Polycations: Effect of Increasing Confinement on the Modes of Interaction of Spermidine3+ With DNA Double Helices.

Polyamines have important roles in the modulation of the cellular function and are ubiquitous in cells. The polyamines putrescine2+, spermidine3+, and spermine4+ represent the most abundant organic counterions of the negatively charged DNA in the cellular nucleus. These polyamines are known to stabilize the DNA structure and, depending on their concentration and additional salt composition, to induce DNA aggregation, which is often referred to as condensation. However, the modes of interactions of these elongated polycations with DNA and how they promote condensation are still not clear. In the present work, atomistic molecular dynamics (MD) computer simulations of two DNA fragments surrounded by spermidine3+ (Spd3+) cations were performed to study the structuring of Spd3+ “caged” between DNA molecules. Microsecond time scale simulations, in which the parallel DNA fragments were constrained at three different separations, but allowed to rotate axially and move naturally, provided information on the conformations and relative orientations of surrounding Spm3+ cations as a function of DNA-DNA separation. Novel geometric criteria allowed for the classification of DNA-Spd3+ interaction modes, with special attention given to Spd3+ conformational changes in the space between the two DNA molecules (caged Spd3+). This work shows how changes in the accessible space, or confinement, around DNA affect DNA-Spd3+ interactions, information fundamental to understanding the interactions between DNA and its counterions in environments where DNA is compacted, e.g. in the cellular nucleus.

The Parallel Reaction Monitoring-Parallel Accumulation-Serial Fragmentation (prm-PASEF) Approach for Multiplexed Absolute Quantitation of Proteins in Human Plasma.

Mass spectrometry (MS)-based quantitative proteomic methods have become some of the major tools for protein biomarker discovery and validation. The recently developed parallel reaction monitoring-parallel accumulation-serial fragmentation (prm-PASEF) approach on a Bruker timsTOF Pro mass spectrometer allows the addition of ion mobility as a new dimension to LC-MS-based proteomics and increases proteome coverage at a reduced analysis time. In this study, a prm-PASEF approach was used for the multiplexed absolute quantitation of proteins in human plasma using isotope-labeled peptide standards for 125 plasma proteins, over a broad (104-106) dynamic range. Optimization of LC and MS parameters, such as accumulation time and collision energy, resulted in improved sensitivity for more than half of the targets (73 out of 125 peptides) by increasing the signal-to-noise ratio by a factor of up to 10. Overall, 41 peptides showed up to a 2-fold increase in sensitivity, 25 peptides showed up to a 5-fold increase in sensitivity, and 7 peptides showed up to a 10-fold increase in sensitivity. Implementation of the prm-PASEF method allowed absolute protein quantitation (down to 1.13 fmol) in human plasma samples. A comparison of the concentration values of plasma proteins determined by MRM on a QTRAP instrument and by prm-PASEF on a timsTOF Pro revealed an excellent correlation (R2 = 0.97) with a slope of close to 1 (0.99), demonstrating that prm-PASEF is well suited for "absolute" quantitative proteomics.

Investigation of Effects of the Spectral Library on Analysis of diaPASEF Data

Targeted analysis of data-independent acquisition (DIA) data needs a spectral library, which is generated by data-dependent acquisition (DDA) experiments or directly from DIA data. A comparison of the DDA library and DIA library in analyzing DIA data has been reported. However, the effects of different spectral libraries on the analysis of diaPASEF data have not been investigated. Here, we generate different spectral libraries with varying proteome coverage to analyze parallel accumulation-serial fragmentation (diaPASEF) data. Besides, we also employ the library-free strategy. The library, constructed by extensive fractionation DDA experiments, produces the highest numbers of precursors and proteins but with a high percentage of missing values. The library-free strategy identifies 10-20% fewer proteins than the library-based method but with a high degree of data completeness. A further study shows that the library-free strategy, although it identifies fewer proteins than the library-based method, leads to similar biological conclusions as the library-based method.

A Fragment of the Uṣṇīṣavijayā Dhāraṇī from Turfan Housed in the Museum für Asiatische Kunst in Berlin

This paper deals with an edition of a newly identified fragment of the Uṣṇīṣavijayā Dhāraṇī in Old Uyghur from Turfan, which is preserved in the collection of Museum für Asiatische Kunst (Museum of Asian Art) in Berlin. The fragment basically represents the dhāraṇī part of the Uṣṇīṣavijayā Dhāraṇī in Old Uyghur script. The fragment is compared with the parallel Old Uyghur fragments that also include the dhāraṇī section and are preserved in the Berlin Turfan collection. The transcription and transliteration of the work is given. Its versions in other languages are compared to explore differences between the texts. Finally, a reconstructed text is presented.

Trapped Ion Mobility Spectrometry Reduces Spectral Complexity in Mass Spectrometry-Based Proteomics.

In bottom-up mass spectrometry-based proteomics, deep proteome coverage is limited by high cofragmentation rates. Cofragmentation occurs when more than one analyte is isolated by the quadrupole and the subsequent fragmentation event produces fragment ions of heterogeneous origin. One strategy to reduce cofragmentation rates is through effective peptide separation techniques such as chromatographic separation and, the more recently popularized, ion mobility (IM) spectrometry, which separates peptides by their collisional cross section. Here, we use a computational model to investigate the capability of the trapped IM spectrometry (TIMS) device at effectively separating peptide ions and quantify the separation power of the TIMS device in the context of a parallel accumulation-serial fragmentation (PASEF) workflow. We found that TIMS separation increases the number of interference-free MS1 peptide features 9.2-fold, while decreasing the average peptide density in precursor spectra 6.5-fold. In a data-dependent acquisition PASEF workflow, IM separation increases the number of spectra without cofragmentation by a factor of 4.1 and the number of high-quality spectra 17-fold. Using a categorical model, we estimate that this observed decrease in spectral complexity results in an increased likelihood for peptide spectral matches, which may improve peptide identification rates. In the context of a data-independent acquisition workflow, the reduction in spectral complexity resulting from IM separation is estimated to be equivalent to a 4-fold decrease in the isolation window width (from 25 to 6.5 Da). Our study demonstrates that TIMS separation decreases spectral complexity by reducing cofragmentation rates, suggesting that TIMS separation may contribute toward the high identification rates observed in PASEF workflows.

Brain Alpha Oscillations as a Neurobiological Marker of Postural Control

Although parallel corpora are essential language resources for many natural language processing tasks, they are rare or even not available for many language pairs. Instead, comparable corpora are widely available and contain parallel fragments of information that can be used in applications like statistical machine translation systems. In this research, we propose a generative latent Dirichlet allocation based model for extracting parallel fragments from comparable documents without using any initial parallel data or bilingual lexicon. The experimental results show significant improvement if the extracted fragments generated by the proposed method are used for augmenting an existing parallel corpus in an statistical machine translation system. According to the human judgment, the accuracy of the proposed method for an English-Persian task is about 59.7%. Also, the out of vocabulary error rate for the same task is reduced by 28%.

DIA-Based Proteome Profiling of Nasopharyngeal Swabs from COVID-19 Patients.

Since the recent outbreak of COVID-19, there have been intense efforts to understand viral pathogenesis and host immune response to combat SARS-CoV-2. It has become evident that different host alterations can be identified in SARS-CoV-2 infection based on whether infected cells, animal models or clinical samples are studied. Although nasopharyngeal swabs are routinely collected for SARS-CoV-2 detection by RT-PCR testing, host alterations in the nasopharynx at the proteomic level have not been systematically investigated. Thus, we sought to characterize the host response through global proteome profiling of nasopharyngeal swab specimens. A mass spectrometer combining trapped ion mobility spectrometry (TIMS) and high-resolution QTOF mass spectrometer with parallel accumulation-serial fragmentation (PASEF) was deployed for unbiased proteome profiling. First, deep proteome profiling of pooled nasopharyngeal swab samples was performed in the PASEF enabled DDA mode, which identified 7723 proteins that were then used to generate a spectral library. This approach provided peptide level evidence of five missing proteins for which MS/MS spectrum and mobilograms were validated with synthetic peptides. Subsequently, quantitative proteomic profiling was carried out for 90 individual nasopharyngeal swab samples (45 positive and 45 negative) in DIA combined with PASEF, termed as diaPASEF mode, which resulted in a total of 5023 protein identifications. Of these, 577 proteins were found to be upregulated in SARS-CoV-2 positive samples. Functional analysis of these upregulated proteins revealed alterations in several biological processes including innate immune response, viral protein assembly, and exocytosis. To the best of our knowledge, this study is the first to deploy diaPASEF for quantitative proteomic profiling of clinical samples and shows the feasibility of adopting such an approach to understand mechanisms and pathways altered in diseases.

Ultrafast and Reproducible Proteomics from Small Amounts of Heart Tissue Enabled by Azo and timsTOF Pro.

Global bottom-up mass spectrometry (MS)-based proteomics is widely used for protein identification and quantification to achieve a comprehensive understanding of the composition, structure, and function of the proteome. However, traditional sample preparation methods are time-consuming, typically including overnight tryptic digestion, extensive sample cleanup to remove MS-incompatible surfactants, and offline sample fractionation to reduce proteome complexity prior to online liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Thus, there is a need for a fast, robust, and reproducible method for protein identification and quantification from complex proteomes. Herein, we developed an ultrafast bottom-up proteomics method enabled by Azo, a photocleavable, MS-compatible surfactant that effectively solubilizes proteins and promotes rapid tryptic digestion, combined with the Bruker timsTOF Pro, which enables deeper proteome coverage through trapped ion mobility spectrometry (TIMS) and parallel accumulation-serial fragmentation (PASEF) of peptides. We applied this method to analyze the complex human cardiac proteome and identified nearly 4000 protein groups from as little as 1 mg of human heart tissue in a single one-dimensional LC-TIMS-MS/MS run with high reproducibility. Overall, we anticipate this ultrafast, robust, and reproducible bottom-up method empowered by both Azo and the timsTOF Pro will be generally applicable and greatly accelerate the throughput of large-scale quantitative proteomic studies. Raw data are available via the MassIVE repository with identifier MSV000087476.