scholarly journals Identification of Differentiating Metabolic Pathways between Infant Gut Microbiome Populations Reveals Depletion of Function-Level Adaptation to Human Milk in the Finnish Population

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Jan Majta ◽  
Krzysztof Odrzywolek ◽  
Bozena Milanovic ◽  
Vladyslav Hubar ◽  
Sonia Wrobel ◽  
...  
Keyword(s):  
Human Milk ◽  
The Novel ◽  
Finnish Population ◽  
Specific Composition ◽  
Infant Gut Microbiome ◽  
Novel Method ◽  
Analysis Of Function ◽  
Taxonomic Annotation ◽  
Level Analysis

ABSTRACT A variety of autoimmune and allergy events are becoming increasingly common, especially in Western countries. Some pieces of research link such conditions with the composition of microbiota during infancy. In this period, the predominant form of nutrition for gut microbiota is oligosaccharides from human milk (HMO). A number of gut-colonizing strains, such as Bifidobacterium and Bacteroides, are able to utilize HMO, but only some Bifidobacterium strains have evolved to digest the specific composition of human oligosaccharides. Differences in the proportions of the two genera that are able to utilize HMO have already been associated with the frequency of allergies and autoimmune diseases in the Finnish and the Russian populations. Our results show that differences in terms of the taxonomic annotation do not explain the reason for the differences in the Bifidobacterium/Bacteroides ratio between the Finnish and the Russian populations. In this paper, we present the results of function-level analysis. Unlike the typical workflow for gene abundance analysis, BiomeScout technology explains the differences in the Bifidobacterium/Bacteroides ratio. Our research shows the differences in the abundances of the two enzymes that are crucial for the utilization of short type 1 oligosaccharides. IMPORTANCE Knowing the limitations of taxonomy-based research, there is an emerging need for the development of higher-resolution techniques. The significance of this research is demonstrated by the novel method used for the analysis of function-level metagenomes. BiomeScout—the presented technology—utilizes proprietary algorithms for the detection of differences between functionalities present in metagenomic samples.

scholarly journals A novel class of human milk oligosaccharides based on 6-galactosyllactose and containing N-acetylglucosamine branches extended by oligogalactoses

2021 ◽  
Author(s):  
Franz-Georg Hanisch ◽  
Clemens Kunz
Keyword(s):  
Human Milk ◽  
Infant Nutrition ◽  
Maldi Mass Spectrometry ◽  
The Novel ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
New Class ◽  
Terminal Galactose ◽  
Branched Chains

Human milk oligosaccharides (HMOs) have attracted much attention in recent years not only as a prebiotic factor, but in particular as an essential component in infant nutrition related to their impact in innate immunity. The backbone structures of complex HMOs generally contain single or repetitive lacto-N-biose (type 1) or lactosamine (type 2) units in either linear or branched chains extending from a lactose core. While all known branched structures originate from 3,6-substitution of the lactosyl core galactose, we here describe a new class of HMOs that tentatively branch at terminal galactose of 6-galactosyllactose. Another novel feature of this class of HMOs was found in linear oligo-galactosyl chains linked to one of the N-acetylglucosamine (GlcNAc) branches. The novel structures exhibit general formulas with hexose vs. hexosamine contents of 5/2 to 8/2 and can be designated as high-galactose (HG)-HMOs. In addition, up to three fucosyl residues are linked to the octa- to dodecasaccharides, which were detected in two human milk samples from Lewis blood group defined donors. Structural analyses of methylated glycans and their alditols comprised MALDI mass spectrometry, ESI-(CID)MS and linkage analyses by GC-MS of the derived partially methylated alditol acetates. Enzymatic degradation by application of β1-3,4-specific galactosidase supported the presence of terminal galactose linked [beta]1-6 to one of the two GlcNAc branches.

A novel method for the determination of linting propensity of paper

TAPPI Journal ◽  
2012 ◽  
Vol 11 (10) ◽  
pp. 9-17
Author(s):  
ALESSANDRA GERLI ◽  
LEENDERT C. EIGENBROOD
Keyword(s):  
Ash Content ◽  
The Novel ◽  
Offset Printing ◽  
Excellent Correlation ◽  
End Conditions ◽  
Bottom Side ◽  
Novel Method ◽  
Total Fraction

A novel method was developed for the determination of linting propensity of paper based on printing with an IGT printability tester and image analysis of the printed strips. On average, the total fraction of the surface removed as lint during printing is 0.01%-0.1%. This value is lower than those reported in most laboratory printing tests, and more representative of commercial offset printing applications. Newsprint paper produced on a roll/blade former machine was evaluated for linting propensity using the novel method and also printed on a commercial coldset offset press. Laboratory and commercial printing results matched well, showing that linting was higher for the bottom side of paper than for the top side, and that linting could be reduced on both sides by application of a dry-strength additive. In a second case study, varying wet-end conditions were used on a hybrid former machine to produce four paper reels, with the goal of matching the low linting propensity of the paper produced on a machine with gap former configuration. We found that the retention program, by improving fiber fines retention, substantially reduced the linting propensity of the paper produced on the hybrid former machine. The papers were also printed on a commercial coldset offset press. An excellent correlation was found between the total lint area removed from the bottom side of the paper samples during laboratory printing and lint collected on halftone areas of the first upper printing unit after 45000 copies. Finally, the method was applied to determine the linting propensity of highly filled supercalendered paper produced on a hybrid former machine. In this case, the linting propensity of the bottom side of paper correlated with its ash content.

The Free Responsible Action of the Individual

2018 ◽  
Author(s):  
Michael P. DeJonge
Keyword(s):  
The Novel ◽  
Extreme Situation ◽  
The Third ◽  
Third Phase ◽  
Responsible Action ◽  
Action Type ◽  
Two Phases ◽  
The Individual ◽  
The Church

If, as Chapter 12 argues, much of Bonhoeffer’s resistance thinking remains stable even as he undertakes the novel conspiratorial resistance, what is new in his resistance thinking in the third phase? What receives new theological elaboration is the resistance activity of the individual, which in the first two phases was overshadowed by the resistance role played by the church. Indeed, as this chapter shows, Bonhoeffer’s conspiratorial activity is associated with what he calls free responsible action (type 6), and this is the action of the individual, not the church, in the exercise of vocation. As such, the conspiratorial activity is most closely related to the previously developed type 1 resistance, which includes individual vocational action in response to state injustice. But the conspiratorial activity differs from type 1 resistance as individual vocational action in the extreme situation.

575 Regression by hetIL-15 monotherapy in different mouse breast cancer models correlates with intratumoral infiltration of a novel population of dendritic cells

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A609-A609
Author(s):  
Sevasti Karaliota ◽  
Dimitris Stellas ◽  
Vasiliki Stravokefalou ◽  
Bethany Nagy ◽  
Cristina Bergamaschi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dendritic Cells ◽  
Nk Cells ◽  
Flow Analysis ◽  
Laboratory Animals ◽  
Tumor Infiltration ◽  
The Novel ◽  
Phenotypic Profile ◽  
Conventional Type

BackgroundIL-15 is a cytokine which stimulates the proliferation and cytotoxic function of CD8+ T and NK cells. We have produced and applied the native heterodimeric IL-15 (hetIL-15) on several preclinical models, which have supported the anti-tumor activity of hetIL-15. Based on these results, hetIL-15 has advanced to clinical trials. The objectives of this study were to explore how hetIL-15 shapes the tumor microenviroment and to characterize the interactions between tumor-infiltrating lymphoid and myeloid cells.MethodsWe studied the efficacy of locoregional administration of heterodimeric IL-15 (hetIL-15) in two different orthotopic triple-negative breast cancer (TNBC) mouse models, syngeneic for C57BL/6 and Balb/c, respectively. The effects of hetIL-15 on immune cells were analyzed by flow cytometry, immunohistochemistry (IHC) and gene expression profiling. The profile of the novel infiltrated dendritic cell populations was further explored by bulk and single cell RNAseq.Results hetIL-15 resulted in tumor eradication in 40% of treated mice and reduction of metastasis. Subsequent rechallenges with the same cell line failed to generate tumor regrowth, suggesting the development of immunological memory in hetIL-15 treated mice. hetIL-15 promoted tumor accumulation of proliferating and cytotoxic CD8+ T and NK cells. Additionally, peritumoral hetIL-15 administration resulted in an increased tumor infiltration of both conventional type 1 dendritic cells (cDC1s) and of a novel DC population found only in the hetIL-15 treated animals. Phenotypic profile analysis confirmed the expression of several cDC1 specific markers, including CD103 and IRF8 on this DC population.Transcriptomics and flow analysis of intratumoral dendritic cells indicate that the new hetIL-15 induced cells reside preferentially in the tumors and are distinct from cDC1 and cDC2 populations. Both cDC1s and the novel DC population were inversely correlated with the tumor size.ConclusionsLocoregional administration of hetIL-15 results in complete eradication of EO771 and significant reduction of 4T1 primary breast cancer tumors, prolonged survival and long-lasting specific anti-tumor immunity. hetIL-15 increases the tumor infiltration of activated T and NK cells and intensifies the tumor infiltration of conventional type 1 dendritic cells (cDC1) and a new population of dendritic cells. We propose that the anti-cancer activity of hetIL-15 in primary EO771 tumors is orchestrated by the interplay of NK, CD8+T cells, cDC1 and a novel subset of DCs with a distinct phenotypic profile. These findings suggest a role for hetIL-15 in the treatment of breast cancer.Ethics ApprovalThe study was approved by the National Cancer Institute-Frederick Animal Care and Use Committee, approval number 19–324 and was conducted in accordance with the ACUC guidelines and the NIH Guide for the Care and Use of Laboratory Animals.

scholarly journals REMAXINT: a two-mode clustering-based method for statistical inference on two-way interaction

2021 ◽  
Author(s):  
Zaheer Ahmed ◽  
Alberto Cassese ◽  
Gerard van Breukelen ◽  
Jan Schepers
Keyword(s):  
Null Hypothesis ◽  
Type I Error ◽  
Type I ◽  
The Novel ◽  
Simulation Studies ◽  
Test Statistic ◽  
Clustering Model ◽  
Novel Method ◽  
Main Effects ◽  
Empirical Case Studies

AbstractWe present a novel method, REMAXINT, that captures the gist of two-way interaction in row by column (i.e., two-mode) data, with one observation per cell. REMAXINT is a probabilistic two-mode clustering model that yields two-mode partitions with maximal interaction between row and column clusters. For estimation of the parameters of REMAXINT, we maximize a conditional classification likelihood in which the random row (or column) main effects are conditioned out. For testing the null hypothesis of no interaction between row and column clusters, we propose a $$max-F$$ m a x - F test statistic and discuss its properties. We develop a Monte Carlo approach to obtain its sampling distribution under the null hypothesis. We evaluate the performance of the method through simulation studies. Specifically, for selected values of data size and (true) numbers of clusters, we obtain critical values of the $$max-F$$ m a x - F statistic, determine empirical Type I error rate of the proposed inferential procedure and study its power to reject the null hypothesis. Next, we show that the novel method is useful in a variety of applications by presenting two empirical case studies and end with some concluding remarks.

scholarly journals Interrogating the Egypto-Sudanic Arabic Connection

Languages ◽  
2021 ◽  
Vol 6 (3) ◽  
pp. 123
Author(s):  
Thomas A. Leddy-Cecere
Keyword(s):  
The Novel ◽  
Present Contribution ◽  
Phonological Processes ◽  
Verbal Inflection ◽  
Segmental Phonology ◽  
Language Data ◽  
History Of ◽  
Novel Method ◽  
Dialect Classification ◽  
Arabic Speaking

The Arabic dialectology literature repeatedly asserts the existence of a macro-level classificatory relationship binding the Arabic speech varieties of the combined Egypto-Sudanic area. This proposal, though oft-encountered, has not previously been formulated in reference to extensive linguistic criteria, but is instead framed primarily on the nonlinguistic premise of historical demographic and genealogical relationships joining the Arabic-speaking communities of the region. The present contribution provides a linguistically based evaluation of this proposed dialectal grouping, to assess whether the postulated dialectal unity is meaningfully borne out by available language data. Isoglosses from the domains of segmental phonology, phonological processes, pronominal morphology, verbal inflection, and syntax are analyzed across six dialects representing Arabic speech in the region. These are shown to offer minimal support for a unified Egypto-Sudanic dialect classification, but instead to indicate a significant north–south differentiation within the sample—a finding further qualified via application of the novel method of Historical Glottometry developed by François and Kalyan. The investigation concludes with reflection on the implications of these results on the understandings of the correspondence between linguistic and human genealogical relationships in the history of Arabic and in dialectological practice more broadly.

scholarly journals Suspended Sediment Modeling Using a Heuristic Regression Method Hybridized with Kmeans Clustering

2021 ◽  
Vol 13 (9) ◽  
pp. 4648
Author(s):  
Rana Muhammad Adnan ◽  
Kulwinder Singh Parmar ◽  
Salim Heddam ◽  
Shamsuddin Shahid ◽  
Ozgur Kisi
Keyword(s):  
Clustering Algorithm ◽  
Suspended Sediments ◽  
Ecological Impacts ◽  
Accurate Estimation ◽  
Data Sets ◽  
The Novel ◽  
Neuro Fuzzy ◽  
Adaptive Regression ◽  
Novel Method ◽  
Model Training

The accurate estimation of suspended sediments (SSs) carries significance in determining the volume of dam storage, river carrying capacity, pollution susceptibility, soil erosion potential, aquatic ecological impacts, and the design and operation of hydraulic structures. The presented study proposes a new method for accurately estimating daily SSs using antecedent discharge and sediment information. The novel method is developed by hybridizing the multivariate adaptive regression spline (MARS) and the Kmeans clustering algorithm (MARS–KM). The proposed method’s efficacy is established by comparing its performance with the adaptive neuro-fuzzy system (ANFIS), MARS, and M5 tree (M5Tree) models in predicting SSs at two stations situated on the Yangtze River of China, according to the three assessment measurements, RMSE, MAE, and NSE. Two modeling scenarios are employed; data are divided into 50–50% for model training and testing in the first scenario, and the training and test data sets are swapped in the second scenario. In Guangyuan Station, the MARS–KM showed a performance improvement compared to ANFIS, MARS, and M5Tree methods in term of RMSE by 39%, 30%, and 18% in the first scenario and by 24%, 22%, and 8% in the second scenario, respectively, while the improvement in RMSE of ANFIS, MARS, and M5Tree was 34%, 26%, and 27% in the first scenario and 7%, 16%, and 6% in the second scenario, respectively, at Beibei Station. Additionally, the MARS–KM models provided much more satisfactory estimates using only discharge values as inputs.

scholarly journals The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 509 ◽  
Author(s):  
Steffen Glöckner ◽  
Khang Ngo ◽  
Björn Wagner ◽  
Andreas Heine ◽  
Gerhard Klebe
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
The Novel ◽  
Binding Modes ◽  
X Ray ◽  
Structure Activity ◽  
Small Set ◽  
Novel Method ◽  
Human Carbonic Anhydrase ◽  
Kinetics Of

The fluorination of lead-like compounds is a common tool in medicinal chemistry to alter molecular properties in various ways and with different goals. We herein present a detailed study of the binding of fluorinated benzenesulfonamides to human Carbonic Anhydrase II by complementing macromolecular X-ray crystallographic observations with thermodynamic and kinetic data collected with the novel method of kinITC. Our findings comprise so far unknown alternative binding modes in the crystalline state for some of the investigated compounds as well as complex thermodynamic and kinetic structure-activity relationships. They suggest that fluorination of the benzenesulfonamide core is especially advantageous in one position with respect to the kinetic signatures of binding and that a higher degree of fluorination does not necessarily provide for a higher affinity or more favorable kinetic binding profiles. Lastly, we propose a relationship between the kinetics of binding and ligand acidity based on a small set of compounds with similar substitution patterns.

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