Small Constituents Research Articles

A size-switchable nanocluster remodels the immunosuppressive microenvironment of tumor and tumor-draining lymph nodes for improved cancer immunotherapy

Remodeling the immunosuppressive tumor microenvironment (TME) by immunomodulators has been well studied in the past years. However, strategies that enable concurrent modulation of both the immunosuppressive TME and tumor-draining lymph nodes (TDLNs) are still in the infancy. Here, we report a pH-sensitive size-switchable nanocluster, SPN-R848, to achieve simultaneous accumulation in tumor and TDLNs for immune activation. SPN-R848 with original size around 150 nm was formed by self-assembly of resiquimod (R848)-conjugated polyamidoamine (PAMAM) derivative, which could disintegrate into its small constituents (～ 8 nm) upon exposure to tumor acidity. The size reduction not only enhanced their accumulation and perfusion in the primary tumor, but promoted their transport and distribution in TDLNs. Accordingly, SPN-R848 remarkably remodeled the immunosuppressive TME by polarizing M2 to M1 macrophages and activated dendritic cells (DCs) in TDLNs, which synergistically facilitated the production and stimulation of cytotoxic T cells, and inhibited tumor growth in breast cancer and melanoma mouse models. Our study suggests that co-activation of immune microenvironments in both tumor and TDLNs may represent a promising direction to elicit strong antitumor immunity.

Нерелятивистское приближение в 39-компонентной теории для частицы со спином 2

The goal of the present paper is investigation of the nonrelativistic approximation in the 39-component theory for a spin 2 particle. We apply explicit expressions for four main matrices Γa with dimension 39×39 in the relevant first-order system of equations, written in Cartesian coordinates and in presence of external electromagnetic fields. For distinguishing the large and small constituents in the complete wave function, we apply three projective operators constructed on the base of the minimal polynomial of the 7-th order for the matrix Γ0. The relevant large and small components are found in explicit form. In each group, we have found independent variables; in particular, among the large components there exist only five independent ones. We have derived the nonrelativistic equation for 5-component wave function; it has the term describing interaction of the magnetic moment of the spin 2 particle with the external magnetic field we distinguished. This additional term is constructed by the projections of spin operator Si and the components of the magnetic field Bi.

Molecular heterostructured interlayer for fabrication of high-performance thin film composite reverse osmosis membranes

To solve the scarcity of fresh water, reverse osmosis (RO) technology for seawater desalination and wastewater reuse has been developed rapidly. However, the performance of RO is limited by poor selectivity towards certain harmful small molecule constituents (e.g., boron in seawater and N-nitrosodimethylamine in wastewater) and the permeability-selectivity trade-off. Herein, a metal polyphenol network interlayer including both hydrophobic zone and monomer adsorption zone is proposed to optimize interfacial polymerization (IP) process for fabrication of RO membrane. This heterogeneous characteristic is endowed by well-chosen phenol (i.e. TTSBI) and metal (Ni). The physicochemical properties of the substrate are also optimized. An ultra-selective RO membrane with thinner separation layer, higher crosslinking degree and larger surface area is obtained. The RO membranes exhibit separation performance beyond the upper selectivity limit for NaCl and hazardous small molecules. The membrane water permeance is 3.50 L m−2h−1bar−1while the NaCl rejection is 99.5 %. Meanwhile, the mechanism of the interlayer influencing IP process is investigated by combining molecular simulation and experimental methods. Our work provides a novel design direction of substrate used for fabricating RO membrane with outstanding performance.

Sodium-enriched nectar shapes plant-pollinator interactions in a subalpine meadow.

Many plants have evolved nutrient rewards to attract pollinators to flowers, but most research has focused on the sugar content of floral nectar resources. Concentrations of sodium in floral nectar (a micronutrient in low concentrations in nectar) can vary substantially both among and within co-occurring species. It is hypothesized that sodium concentrations in floral nectar might play an important and underappreciated role in plant-pollinator interactions, especially because many animals, including pollinators, are sodium limited in nature. Yet, the consequences of variation in sodium concentrations in floral nectar remain largely unexplored. Here, we investigate whether enriching floral nectar with sodium influences the composition, diversity, and frequency of plant-pollinator interactions. We experimentally enriched sodium concentrations in four plant species in a subalpine meadow in Colorado, USA. We found that flowers with sodium-enriched nectar received more visits from a greater diversity of pollinators throughout the season. Different pollinator species foraged more frequently on flowers enriched with sodium and showed evidence of other changes to foraging behavior, including greater dietary evenness. These findings are consistent with the "salty nectar hypothesis," providing evidence for the importance of sodium limitation in pollinators and suggesting that even small nectar constituents can shape plant-pollinator interactions.

지역소멸의 위기에 따른 민주주의의 약화와 대응 방안

In today’s Korean society, the crisis of rapid decline in local population, coupled with a decreasing population, poses one of the biggest challenges in preparing for future generations. Moreover, the issue of rapid decline in local population may present a significant threat to democracy, a foundational principle of the Constitution, beyond just being a concern at the level of industrial or administrative policies for balanced regional development. This article points out that democracy is also weakening due to the crisis of rapid decline in local population, and proposes solutions in terms of the implementation of democracy, focusing on institutions such as elections, political parties, and direct democracy. Firstly, from the perspective of localities and regional populations, there are issues with the proportionality of electoral districts and regional representation. As an extreme imbalance in population between metropolitan and non-metropolitan areas forms, the citizens of the latter experience weakened representation in the election of their legislators, leading to the emergence of large electoral districts or the abnormal setting of a single district for areas lacking regional homogeneity or community cohesion. Under the current small constituency plurality system, maintaining strict population proportionality presents a difficult challenge to overcome. To harmonize the proportionality of electoral district populations with regional representation, considering a constitutional amendment to transform the unicameral legislature to a bicameral system where the upper house has regional representation, or adopting a regional proportional representation system for legislative elections, are potential institutional changes that should be explored. Secondly, recognizing regional political parties as a way to promote local democracy could help enhance local political autonomy. Current Party Law recognizes only national parties, and the Constitutional Court has upheld these provisions. However, the essential function of a party is to participate in the formation of political will of the people, which does not necessarily have to be nationwide. Recognizing regional parties could bolster local democracy and should be considered for enhancement. Thirdly, in response to regional issues more actively and flexibly, the diversification of local government structures should be actively recognized, and strengthening direct democracy measures is necessary to address issues in areas experiencing extreme population decline.

Synthesis and Promising Applications of Graphene and Related Materials

In recent years, there has been extensive research on graphene and its derivatives, driven by their remarkable physicochemical and functional properties. Various forms of graphene, such as multi-layer graphene, graphene oxide, and graphene quantum dots, have shown immense potential to revolutionize multiple technologies. This review critically examines the synthesis and applications of graphene and related materials. In the synthesis section, we explore methods ranging from top-down techniques, which involve breaking down larger structures into graphene layers, to bottom-up approaches, where graphene is built up from smaller constituents. In the application segment, we comprehensively discuss the diverse uses of graphene and its derivatives. This includes their roles in electronic applications, energy storage systems, tribological applications, healthcare technologies, water desalination processes, and mechanical applications. By exploring various applications, we aim to highlight the wide-spread applications of graphene-based materials and their composites in shaping the future of multiple technologies.

Simultaneous degradation and rejection of PPCPs from wastewater in a 3DEO-FO-RO process

This study established a novel three-dimensional electrochemical oxidation coupled with forward osmosis and reverse osmosis (3DEO-FO-RO) system with the purpose to achieve simultaneous degradation and rejection of pharmaceuticals and personal care products (PPCPs) in wastewater. 18 frequently detected PPCPs were selected as the target pollutants to prepare the synthetic wastewater with a concentration of 200 μg/L for each pollutant. Ti/IrO2–Ta2O5–SnO2 mesh anode, titanium mesh cathode and Sn–Sb–Bi/γ-Al2O3 particles electrodes were integrated in the 3DEO-FO reactor. Experimental results demonstrated that degradation efficiency exceeding 98.5 % and rejection exceeding 99.4 % for each PPCP were achieved simultaneously in the 3DEO-FO-RO processes at a current density of 1 mA/cm2 after 8 h treatment. Despite variations in applied current density, the 3DEO-FO-RO processes exhibited superior PPCPs removal efficiencies, particularly for refractory compounds, compared to the 2DEO-FO-RO processes. Increased hydroxyl radical (·OH) generation in the 3D reactor was considered to be responsible for the excellent performance. Furthermore, results derived from ultraviolet (UV) absorption spectra and fluorescence excitation-emission matrix (EEM) spectra provided additional validation for the effective removal of PPCPs in the 3DEO-FO-RO processes, along with evidence indicating the decomposition of PPCPs into smaller constituents. Ultimately, the 3DEO-FO-RO process demonstrated its capacity in removing PPCPs from actual secondary effluent from a wastewater treatment plant. This integrated system coupling 3D EO with FO-RO membranes can provide an efficient approach for simultaneous degradation and rejection of trace contaminants for wastewater reuse.

Constituent Attention for Vision Transformers

Multi-head self-attention (MSA) endows vision Transformers (ViTs) with the ability of modeling long-range interactions between tokens. However, recent works have uncovered that current arbitrary attention makes tokens distracted by extraneous dependencies, complicating the understanding of ViTs and hindering the overall optimization of ViTs. In this paper, we propose Constituent Attention (CA), a straightforward yet effective constraint on MSA to resolve aforementioned issues in different variants of ViTs with negligible overhead. Specifically, CA is designed to encourage the mutual attention between spatially connectable tokens via gathering such token pairs to the same group (termed constituent). Furthermore, with the layers going deeper in ViTs, small adjacent constituents are gradually merged into larger ones, exploring hierarchical structures in the visual objectives. Extensive experiments on four popular benchmarks demonstrate that CA assists the optimization of ViTs and contributes to significant performance gains especially at data-scarce scenarios. Moreover, the layer-wise reasoning mechanism aids ViTs in more consistent and progressive attention across different layers, rendering the inner workings easier to interpret. Our code is publicly available at https://github.com/zju-vipa/ConstituentAttention.

Transforming CS Curricula into EU-Standardized Micro-Credentials

Micro-credentials are a way to integrate flexible learning pathways into the classic forms of education defined in the European Qualification Framework (EQF). They allow members of the workforce to get necessary skills described, certified, and recognized in a transparent and portable way. One way for universities to enter this market for lifelong learning is to convert existing study programs into smaller units, namely, micro-credentials. This process of converting a study program consisting of modules into small, independent pieces is called unbundling. When unbundling a program, the existing modules have to be converted to a standard EU-wide recognizable form. In this paper, we will describe the process we used to convert modules from our study program at DHBW. The first step converts the skill descriptions into a standard form. Since there is no common accepted formal standard, we use the Dublin descriptors as a way to structure the skills on the different abstraction levels, and ESCO-terms as a widely used standardized vocabulary. The second step breaks down modules of 3-12 ECTS into smaller constituents (each ECTS corresponds to a workload of around 30 hours). Typical micro-credentials have a size of 1 to 3 ECTS, a group or stack of micro-credentials corresponds to one module. Keywords: micro-credentials, curriculum design, internationalization, computer science, learning outcomes, standardization

Musical Evidence for Low Boundary Tones in Ancient Greek

Abstract Several scholars have suggested that in ancient Greek there was a low boundary tone at the end of a relatively small prosodic constituent such as a clitic group or maximal prosodic word. The boundary tone may phonologically motivate some puzzling pitch-accentual phenomena in the language. One is the diachronic pitch-peak retraction that led to the circumflex pitch accent (HL) on penultimate syllables (the “sōtêra rule”). Another is the intonational phrase-internal downstepping or deletion of a word-final acute accent (H); that conversion of an acute to a grave accent is known as “lulling” or “koímēsis”. If such a low boundary tone existed, its effects should still be audible in ancient Greek non-strophic vocal music, where there is a significant correlation between the pitch movement of the text and the movement of the melody to which it is set, i.e. between tone and tune. Specifically, proponents of such a low boundary tone would predict that the turning point between falling and rising melody, the “musical trough”, should center around the word-final mora or syllable. The present study provides the first full description of troughs in the Delphic Hymns and finds that they are indeed closely aligned with word-end. Furthermore, once other factors that could lead to word-final troughs are set aside, i.e. once potential confounds are controlled for, the association of the trough with word-end remains strong, suggesting that we should in fact reconstruct the low boundary tone.

Extracellular Vesicles and Particles Modulate Proton Secretion in a Model of Human Parietal Cells.

The secretion of extracellular vesicles and particles (EVPs) is an important mechanism of cellular communication. In this work, we demonstrate a functional role of EVPs in mechanisms regulating gastric acid secretion. HGT-1 cells were used as a model system to assess proton secretion. First, in order to prove EVP secretion by HGT-1 cells, EVPs were isolated by size exclusion chromatography and characterized by nanoparticle tracking analysis, Western blot, and cryo transmission electron microscopy. For examination of the potential role of EVPs in proton secretion, HGT-1 cells were treated with pharmacological EV-inhibitors, resulting in a reduction of histamine-induced proton secretion. To demonstrate the functional role of EVPs in the mechanism of proton secretion, EVP-conditioned supernatant was collected after stimulation of HGT-1 cells with histamine, fractionated, and subjected to an activity screening. The results revealed constituents of the HGT-1-derived secretome with an MW of >100 kDa (including EVPs) to modulate proton secretion, while smaller constituents had no effect. Finally, a dose-dependent modulatory effect on proton secretion of HGT-1 cells was demonstrated by isolated HGT-1-derived EVPs. Hence, this study presents first results on the potential function of EVPs as a previously undiscovered mechanism of regulation of gastric acid secretion by parietal cells.

A Review of Ganoderma Triterpenoids and Their Bioactivities.

For centuries, Ganoderma has been used as a traditional medicine in Asian countries to prevent and treat various diseases. Numerous publications are stating that Ganoderma species have a variety of beneficial medicinal properties, and investigations on different metabolic regulations of Ganoderma species, extracts or isolated compounds have been performed both in vitro and in vivo. However, it has frequently been questioned whether Ganoderma is simply a dietary supplement for health or just a useful "medication" for restorative purposes. More than 600 chemical compounds including alkaloids, meroterpenoids, nucleobases, nucleosides, polysaccharides, proteins, steroids and triterpenes were extracted and identified from Ganoderma, with triterpenes serving as the primary components. In recent years, Ganoderma triterpenes and other small molecular constituents have aroused the interest of chemists and pharmacologists. Meanwhile, considering the significance of the triterpene constituents in the development of new drugs, this review describes 495 compounds from 25 Ganoderma species published between 1984 and 2022, commenting on their source, biosynthetic pathway, identification, biological activities and biosynthesis, together with applications of advanced analytical techniques to the characterization of Ganoderma triterpenoids.

Residents’ trust in local government councils in an emerging nation: effect of political efficacy, good governance and performance

PurposeThis study aims to explore residents’ trust in local government councils and to examine the effect of political efficacy and good governance on that trust and on the performance of local government councils in an emerging nation.Design/methodology/approachData were analysed using qualitative and quantitative research designs. Firstly, a thematic analysis was performed to explore residents’ trust in local government councils and compare it with the data gathered in the literature review. Thereafter, a partial least squares-structural equation modelling (PLS-SEM) approach was used to investigate the hypothesised linkages.FindingsThe thematic analysis of the face-to-face semi-structured interviews discovered four themes (trust, performance, political efficacy and good governance). Additional analysis of these themes via the PLS-SEM approach revealed good governance to be the most influential factor in promoting residents’ trust in local government councils. Political efficacy was the second most influential factor. Residents expect local government councils’ officers to demonstrate a strong commitment to the rule of law and comply with all relevant laws and regulations.Practical implicationsLocal government councils should openly accept residents’ requests and suggestions, be more flexible in policy delivery and be responsive to policy demands given the relatively small constituencies and greater policy latitudes. Multiple avenues should be available for interaction between residents and local government councils in the mission to achieve sustainable urban growth.Originality/valueThis study is unique in that it advances existing research that is lacking in the context of the Malaysian local government council. The result alerts are crucial in that they alert local government councils to the need for high levels of governance and accountability in terms of resident support to gain more trust and confidence.

Lactose Intolerance: A Review for facts and fictions

Milk is assumed to be a complete food, due to its high nutritional status. Regular consumption of milk reduces the problems of nutrition deficiency. Milk contains sugar, mainly lactose in higher amount and lactose, with other ingredients of milk, also contributes to maintain the energy level of body. But, in some cases a problem arises due to the intake of lactose mainly owing to the deficiency of ?-galactosidase (Lactase) enzyme. Deficiency of lactase enzyme in human body, results in inefficiency of body for degrading the lactose into its smaller constituents. Un-degraded/ undigested lactose consumed by the bacteria and converts it into several acids and gases, which results in arise of several types of intestinal disorders. In this article, main focus is given on the lactose intolerance, its types, and remedies.

Polyphenolic Glycosides from the Fruits Extract of Lycium ruthenicum Murr and Their Monoamine Oxidase B Inhibitory and Neuroprotective Activities.

The fruits ofLycium ruthenicum Murr have long been consumed as health food and used in folk medicine in China. Apart from the well-known polysaccharides, the active small molecular constituents in this fruit have not been fully studied. In this work, a systematic phytochemical study was carried out to investigate the small molecules and their potential health benefits. Nine new polyphenolic glycosides, lyciumserin A-I (1-9), together with 16 known compounds (10-25), were isolated and elucidated by high-resolution electrospray ionization mass spectrometry and comprehensive NMR analyses in combination with chemical hydrolysis. Compounds 1, 2, and 16 exhibited moderate inhibitory activity of monoamine oxidase B (MAO-B), while compounds 1 (50 μM) and 2 (100 μM) displayed significant neuroprotective effects (69.22 and 72.38% of cell viability, respectively) in the 6-hydroxydopamine-induced injury of the PC12 cell model (54.41%), comparable to the positive drug rasagiline (70.45%). The neuroprotective effect of 1 and 2 was further evidenced by the observation of the morphological change and fluorescein diacetate/propidium iodide staining. In addition, the levels of the major active compounds (1, 3, 5/6, and 16-18) vary from 21.5 to 892.3 μg/g. This is the first report on phenolic glycosides from the fruits ofL. ruthenicum Murr that possess both significant MAO-B inhibitory and neuroprotective effects, indicating the promising potential of the fruits for the development of health care products and even therapeutic agents for the treatment of Parkinson's disease and other neurodegenerative diseases.

STRUCTURAL ANALYSIS OF CODE-MIXING AMONG JORDANIANS ON FACEBOOK

The main issue of the present aims at investigating the most frequent English categories that Jordanian students tend to use within Arabic discourse on Facebook. Furthermore, the study tries to examine the validity of Polack’s universal constraint ‘size of constituent' and whether Jordanian students tend to mix small constituents like nouns, verbs, adjectives, and adverbs, or they tend to mix large English constituents like clauses and phrases. To this end, a research design involves both quantitative and qualitative approaches was used. The quantitative analysis collected numeric information and used frequency distribution technique. On the other hand, the qualitative analysis collected qualitative data and used thematic analysis technique. The quantitative analysis revealed that Jordanian speakers generally insert both small and large English constituents in their speech; 70% of the inserted English constituents were small while large constituents constituted 29% of the constituents. That means, Jordanians tend to use small English constituents more than large ones. Particularly, nouns are the most frequently used mixed English constituents with (30 %), followed by adjectives which constituted 13% of the mixed English constituents. Accordingly, Poplack's universal constraint of size of constituent is violated. On the other side, the qualitative analysis of the data obtained showed that the size of the inserted English constituents has no effect on Arabic sentence structure and word order, that is, speakers form the sentence according to Arabic language and use constituents that have very limited grammatical restrictions. As a conclusion, Jordanian students use English nouns as the most frequently used English categories. Furthermore, the study provides a theoretical implication that is directed to the Arabic Language Academies in the Arab World. In fact, Arabic Academic are responsible to coin appropriate Arabic categories that meet the need of using English categories. That is, coining new Arabic categories will limit using English categories within Arabic discourse, save Arabic purity, and enrich Arabic language with new terms. Thus, Arabic language have to have new lexicon to develop and stay alive.

Establishment of a faecal DNA quantification technique for rare and cryptic diet constituents in small mammals.

DNA-based approaches have greatly improved the applicability of dietary studies aimed at investigating ecological processes. These studies have provided direct insights into, otherwise difficult to measure, interactions between species and trophic levels, food web structure and ecosystem functioning. However, despite these advances, DNA-based methods have struggled to accurately quantify the whole breadth of diet constituents because of methodological biases, such as amplification bias and digestive processes. The present study is, to our knowledge, the first diet study to use droplet digital PCR to quantify diet constituents. We manipulated the diet of wild-caught wood mice (Apodemus sylvaticus) by feeding them with a known amount of small vegetable seeds (onion and carrot) and quantified the DNA traces of these diet constituents in faecal samples. The sensitivity of the technique combined with the control on the experimental design allowed mitigation of methodological bias. We were able to accurately determine DNA concentrations of small vegetable seeds in the diet of wood mice. Quantification of target DNA demonstrated significant differences in DNA content when one vs. five seeds were consumed. These differences remained significant when the age, sex and other diet constituents of the mice were altered. Different DNA markers, targeting different parts of the chloroplast, influenced onion DNA detectability. However, all onion and carrot markers showed higher DNA content for higher seed numbers. Overall, the sensitive DNA-based approach developed in this study allows for minimally invasive quantification of small diet constituents in faeces, which would otherwise be undetectable with traditional methods.

Quantification of extremely small-structured ferritic-austenitic phase fractions in stainless steels manufactured by laser powder bed fusion

This work investigated processing of stainless steel powders and powder mixtures using powder bed fusion - laser beam/metal (PBF-LB/M), which produced different ferritic and austenitic phase fractions in the as-built state. The rapid cooling and solidification rates in the PBF-LB/M process led to the formation of an extremely small-structured microstructure in which the austenitic phase was found on the grain boundaries and as acicular Widmanstätten austenite (width < 1 µm) within the primary δ-ferritic solidified matrix. This work shows that the time-saving quantification of the ferritic and austenitic phase fractions of these particular microstructures is nontrivial. Common time-efficient phase quantification methods such as image analysis of etched cross-sections or magneto-inductive methods (Feritscope®) have proven to be inaccurate. On the other hand, electron backscattered diffraction (EBSD) investigations proved to be extremely time-consuming in order to resolve the small microstructural constituents sufficiently well and to obtain a reliably large sample section. The highest accuracy was achieved with X-ray diffraction. Two different methods were considered: the Debye-Scherrer method, which was characterized by short measuring times, and the Bragg-Brentano method (quantification using Rietveld refinement), which showed the highest accuracy for the entire range of ferritic-austenitic phase fractions.

Robust and Long-Term Cellular Protein and Enzymatic Activity Preservation in Biomineralized Mammalian Cells.

Preservation of evolved biological structure and function in robust engineering materials is of interest for storage of biological samples before diagnosis and development of vaccines, sensors, and enzymatic reactors and has the potential to avoid cryopreservation and its associated cold-chain issues. Here, we demonstrate that "freezing cells in amorphous silica" is a powerful technique for long-term preservation of whole mammalian cell proteomic structure and function at room temperature. Biomimetic silicification employs the crowded protein microenvironment of mammalian cells as a catalytic framework to proximally transform monomeric silicic acid into silicates forming a nanoscopic silica shell over all biomolecular interfaces. Silicification followed by dehydration preserves and passivates proteomic information within a nanoscale thin silica coating that exhibits size selective permeability (<3.6 nm), preventing protein leaching and protease degradation of cellular contents, while providing access of small molecular constituents for cellular enzymatic reaction. Exposure of dehydrated silicified cells to mild etchant or prolonged hydrolysis removes the silica, completely rerevealing biomolecular components and restoring their accessibility and functionality.

Impact of commercial scale ultrafiltration on the composition of white and rosé wine

Ultrafiltration (UF) was performed on six white and rosé wines, at commercial scale (5400–71,000 L), to remove phenolic compounds associated with astringency. Dynamic UF parameters (permeate flux, transmembrane pressure, temperature) were monitored during filtration, and wine composition compared before and after treatment. Over 90% wine permeation was achieved although flux declined progressively throughout UF and dropped significantly after 80% fractionation. Wine macromolecules, especially phenolics and proteins, were substantially concentrated in retentate, such that the resulting permeate achieved clarification and heat stabilization specifications eliminating the need for fining. Other wine compositional properties (pH, free and total SO2, volatile acidity, and viscosity) were not significantly affected. Membrane fouling resulted in the rejection of small wine constituents (sugars, acids, and low molecular weight phenolics) suggesting complex membrane/solute interactions. To our knowledge, this is the first study to demonstrate the efficacy of UF in producing clarified and stabilized permeate, which reduced the negative effects of excess phenolics and proteins in wine.