Unfolding Process Research Articles

From neighbour to member: Assessing Moldova’s EU membership perspectives

This article examines Moldova’s prospective membership in the European Union (EU) in the wake of the EU’s renewed enlargement drive which was prompted by Russia’s 2022 invasion of Ukraine. It explores the dynamics shaping Moldova’s accession path, spotlighting obstacles to integration that official reports appear to overlook or underplay. The article compares EU and Moldovan documents, civil society reports, and insights from interviews with Moldovan officials and civil society representatives to gain a nuanced picture of the evolving situation. Attention is also given to the distinct characteristics of the currently unfolding enlargement process, including its sense of urgency and geopolitical significance which have led to calls for an expedited or ‘fast-track’ accession. Findings note that despite Moldova’s impressive progress in aligning with EU standards in many areas, substantial hurdles in justice reform, combating corruption and de-oligarchisation persist. Incomplete public administration reforms, uneven civil society involvement in decision-making, and issues associated with the Transnistria conflict also have consequences for Moldova’s EU prospects, especially if an expedited version of enlargement occurs.

Historical Geographical Information System (HGIS): social trajectories of two Chinese historical figures Su Shi and Zuo Zongtang in spatial context

Historical figures have important significance worldwide. This paper introduces the concept of historical Geographical Information System (HGIS) using the lives of two personalities from Chinese history as case studies: Su Shi, a literary figure of the Northern Song Dynasty, and Zuo Zongtang, a military strategist from the late Qing era. By studying the geographical points marking their life activities, their migratory patterns were explored, along with the dynamics of their social networks within time and space, examining the distinctive phases and characteristics of their individual journeys. Kernel density estimation, standard deviation ellipse, location-based distance analysis, and social network graphs were employed in this work. Our findings reveal that Su Shi’s migrations were largely dictated by official appointments, ultimately rooted in imperial successions and factional strife, with his intellectual pursuits significantly influenced by the humanistic milieu. Conversely, Zuo Zongtang’s migrations were predominantly shaped by war, reflecting the challenges of the late Qing era in relation to governance, sovereignty, and diplomacy. The military encampments selected by Zuo Zongtang tended to be situated near water sources, illustrating how his migratory trajectory was influenced by natural geographic conditions. The social circles of these figures are tied to their social and political stature. Through the socio-historic context, the characteristics of these historical figures’ behavioral trajectories relate to the unfolding process of societal and historical development. These insights offer a glimpse into the life journey behind historical figures, implicitly highlighting their perseverance and resilience in adversity, thereby describing innovative approaches to inheriting and disseminating the cultural legacy.

Exploring the unfolding pathways of protein families using Elastic Network Model

We explore how a protein’s native structure determines its unfolding process. We examine how the local structural features, like shear, and the global structural properties, like the number of soft modes, change during unfolding. Simulations are performed using a Gaussian Network Model (GNM) with bond breaking for both thermal and force-induced unfolding scenarios. We find that unfolding starts in areas of high shear in the native structure and progressively spreads to the low shear regions. Interestingly, analysis of single domain protein families (Chymotrypsin inhibitor and Barnase) reveal that proteins with distinct unfolding pathways exhibit divergent behavior of the number of soft modes during unfolding. This suggests that the number of soft modes might be a valuable tool for understanding thermal unfolding pathways. Additionally, we found a strong link between a protein’s overall structural similarity (TM-score) and its unfolding pathways, highlighting the importance of the native structure in determining how a protein unfolds.

Sharp habitat shifts, evolutionary tipping points and rescue: Quantifying the perilous path of a specialist species towards a refugium in a changing environment

Specialist species thriving under specific environmental conditions in narrow geographic ranges are widely recognized as heavily threatened by climate deregulation. Many might rely on both their potential to adapt and to disperse towards a refugium to avoid extinction. It is thus crucial to understand the influence of environmental conditions on the unfolding process of adaptation. Here, I study the eco-evolutionary dynamics of a sexually reproducing specialist species in a two-patch quantitative genetic model with moving optima. Thanks to a separation of ecological and evolutionary time scales and the phase-line study of the selection gradient, I derive the critical environmental speed for persistence, which reflects how the existence of a refugium impacts extinction patterns and how it relates to the cost of dispersal. Moreover, the analysis provides key insights about the dynamics that arise on the path towards this refugium. I show that after an initial increase of population size, there exists a critical environmental speed above which the species crosses a tipping point, resulting into an abrupt habitat switch. In addition, when selection for local adaptation is strong, this habitat switch passes through an evolutionary “death valley”, leading to a phenomenon related to evolutionary rescue, which can promote extinction for lower environmental speeds than the critical one.

Maintenance satellite modular docking mechanism design for on orbit servicing to nanosatellites

PurposeAs a result of space debris problem, it is necessary to deorbit uncontrollable satellites or repair them to extend mission duration to avoid sending a new satellite. The purpose of this paper is to develop a docking mechanism that can be easily customized for different missions, providing on-orbit servicing for nanosatellites.Design/methodology/approachThis research outlines a system and mechanism design for the docking phase of on-orbit servicing to nanosatellites. The umbrella-inspired mechanism is designed with utmost simplicity to minimize the likelihood of failure. CAD, structural analyse and mechanism analyse tools are used for designing and analysing the system. To ensure that the design attains the desired durability, numerous iterations are conducted. A three-dimensional (3D)-printed prototype is generated for mechanism verification in laboratory conditions.FindingsThe aimed mechanism is generated successfully. A 3D-printed prototype is assembled to verify the mechanism. Also, an equation for customis the presented design is generated for different mission requirements in the future.Practical implicationsThe usage of the proposed design can help increase the lifespan of satellites.Originality/valueThe primary innovation in this study is the development of a docking mechanism featuring a movable platform to provide servicing for nanosatellites in orbit. The mechanism presented can be displaced without initiating the unfolding process. This provides a customizable coupling distance for different mission requirements. Therefore, the presented mechanism can serve both different types of satellites and more than one satellite on-orbit with a cost-effective design. Also, the presented design can be easily customized to enable adaptation for the different mission requirements in the future.

Unfolding Prosody Guides the Development of Word Segmentation

Prosody is known to scaffold the learning of language, and thus understanding prosodic development is vital for language acquisition. The present study explored the unfolding prosody model of prosodic development (proposed in Frota’s et al. study in 2016) beyond early production data, to examine whether it predicted the development of early segmentation abilities. European Portuguese-learning infants aged between 5 and 17 months were tested in a series of word segmentation experiments. Developing prosodic structure was evidenced in word segmentation as proposed by the unfolding model: (i) a simple monosyllabic word shape crucially placed at a major prosodic edge was segmented first, before more complex word shapes under similar prosodic conditions; (ii) the segmentation of more complex words was easier at a major prosodic edge than in phrase-medial position; and (iii) the segmentation of complex words with an iambic pattern preceded the segmentation of words with a trochaic pattern. These findings demonstrated that word segmentation evolved with unfolding prosody, suggesting that the prosodic units developed in the unfolding process are used both as speech production planning units and to extract word-forms from continuous speech. Therefore, our study contributes to a better understanding of the mechanisms underlying word segmentation, and to a better understanding of early prosodic development, a cornerstone of language acquisition.

Contribution of ultrasound‐assisted protein structural changes in marinated beef to the improved binding ability of spices and flavor enhancement

AbstractBACKGROUNDMarination is an important part of air‐dried beef processing, and traditional methods are inefficient and produce inconsistent results. Ultrasound, as a novel technology, can be combined with traditional marination methods. The study aimed to investigate the improvement of beef flavor by ultrasound‐assisted marination. At the same time, the potential relationship between the alteration of meat protein and flavor quality by ultrasound‐assisted marinating was further investigated to enable better flavor modulation and research.RESULTSHeadspace solid‐phase microextraction–gas chromatography–mass spectrometry revealed that the spice flavor of beef was significantly enhanced by 500 W ultrasound‐assisted marination. Meanwhile, the experimental results demonstrated that the ultrasound‐assisted marination promoted the unfolding of beef myofibrillar protein structure, which increased the number of hydrophobic and hydrogen bonding sites, enhanced the electrostatic effect and improved the functional properties of the protein. Ultrasound‐assisted marination significantly enhanced the binding ability of beef myofibrillar proteins to flavor compounds compared with conventional marination. An electronic nose confirmed that this resulted in a significant increase in the flavor of the marinated meat.CONCLUSIONUltrasound‐assisted marination effectively enhanced the flavor of marinated meat, which was closely related to the development of protein conformation. The results of this study have important implications for the food industry and the role of protein unfolding processes in flavor modulation. In particular, the findings can be practically applied to improving meat flavor under ultrasound‐assisted marination. © 2024 Society of Chemical Industry.

A Reconfigurable Proangiogenic Hydrogel Patch Enabling Minimally Invasive Drug Delivery.

Hydrogel is widely used for the sustained delivery of bioactive molecules that can treat various injuries, diseases, and tissue defects. However, inserting hydrogel implants without disrupting their functionality and microstructure often requires a large incision, leading to potential complications, such as infection, scarring, and pain. The gel implant is often manually rolled and inserted through a catheter for a minimally invasive delivery. However, success heavily depends on the user's skills, which can inadvertently damage the implant. To address this issue, we developed a reconfigurable hydrogel patch that can self-fold into a small tube and unfold spontaneously after implantation through a catheter. The hydrogel path was assembled by layering a drug-releasing poly(ethylene glycol) diacrylate (PEGDA) hydrogel sheet onto a PEGDA and polyethylenimine (PEI) hydrogel sheet, which rapidly swells and degrades homogeneously at controlled rates. The dynamics of the self-folding and unfolding process could be controlled by differences in the expansion ratio and elastic modulus between the two gel layers according to a mathematical model that closely matched experimental results. The unfolding process triggered a sustained release of the protein cargo. Specifically, the reconfigurable gel loaded with angiopoietin 1 significantly enhanced neovascularization, nearly doubling the vascular density compared to the control group following implantation through a tube with 15% smaller diameter than the original shape of the gel patch. This gel biopatch will be broadly useful for the minimally invasive delivery of a wide array of therapeutic molecules, potentially enhancing therapeutic outcomes.

‘Repeat play’: Musical Minimalism in the Processes of Samuel Beckett’s Late Drama

This essay promotes a focused evaluation of Samuel Beckett’s work in the context of musical minimalism, which it identifies as a closely related and aesthetically significant point of comparison, sharing an attitude towards a work of art as an unfolding process rather than a static product. Beginning with a comparative analysis of Play and Philip Glass’s 1963 score, the origins of Beckett’s connection with minimalist music are explored, with characteristically ‘Beckettian’ ideas shown to be at work in Glass’s compositional idiom. Then, looking ahead twenty years, Beckett’s Quad is examined in light of minimalist music by Steve Reich, whose technologically motivated compositions written in the years between Play and Quad are given as appropriate equivalents for many of the tele-play’s formal peculiarities. By examining Beckett’s work in connection with the unique achievements of minimalist music, we can better define our understanding of Beckett as a ‘minimalist’ working concurrently with a particular artistic movement. Additionally, we can identify common artistic concerns in his work and the music of Glass and Reich, in which highly repetitive patterns, often aided by technology, are employed to emphasise the interrelated processes of conception, performance, and interpretation at work within a piece of art.

Modulation of dynamic DNA G-quadruplex structures in the hTERT promoter region by ligands.

Small molecules can inhibit cellular processes such as replication and transcription by binding to the promoter regions that are prone to form G-quadruplexes. However, since G-quadruplexes exist throughout the human genome, the G-quadruplex binders suffer from specificity issues. To tackle this problem, a G-quadruplex binder (Pyridostatin, or PDS) is conjugated with a ligand (Polyamide, or PA) that can specifically recognize DNA sequences flanking the G-quadruplex forming region. The binding mechanism of this hybrid ligand to the hTERT promoter region (hTERT 5-12) is then elucidated using optical tweezers. During mechanical unfolding processes, different intermediate structures of hTERT 5-12 in presence of PDS, PA, or PA-PDS conjugateare observed. These intermediate structures are consistent with two folding patterns of G-quadruplexes in the hTERT 5-12 fragment. While the duplex DNA binder PA facilitates the folding of a hairpin-G-quadruplex structure, the PDS assists the formation of two tandem G-quadruplexes. Both replication stop assay in vitro and dual luciferase assay in vivo established the effectiveness of the PA-PDS conjugate for hTERT 5-12 targeting. We expect such a ligand dependent folding dynamics will provide guidelines to the development of drugs that not only target hTERT expressions, but also other oncogenes via interactions with specific G-quadruplex structures formed in their promotor regions.

Utilizing Involuntary Unfolding Phenomena as Catalyst for Adaptive Responsiveness and Reorganization

ABSTRACT This paper explores the complex area of so-called unfolding processes and unfolding phenomena in hypnotherapy, emphasizing on unfolding movements and unfolding images, identified as complex involuntary phenomena, which emerge spontaneously without suggestions for these phenomena. Unfolding phenomena are examined as foundational elements of the unfolding process. On the one hand, the study unveils the macro-structure of the unfolding process by categorizing it into involuntary unfolding sets, phases, and unfolding subunits, all of which are analogous among patients and across different organizational levels. On the other hand, detailing the micro-structure aids in elucidating the functionality and elements of the unfolding phenomena. These elements encompass unfolding schemas and instruments. They are emphasized for their role in intrapsychic ideodynamics and responsiveness, aiding recurrent induction aligned and being promoted via an intuitive state of consciousness. Unfolding phenomena elucidate resource elicitation, and adaptation, contributing to the phenotypic organization and reorganization. In this context, the mechanisms of responsiveness, characterized by an unfolding process during hypnotherapy with distinct phases, are examined to help therapists and researchers understand how hypnotherapy can induce phenotypic changes, thereby facilitating treatment, personal growth, and the emergence of a new form of consciousness.

Killing Two Birds with One Stone: Accounting for Unfolding Item Response Process and Response Styles Using Unfolding Item Response Tree Models

Two research streams on responses to Likert-type items have been developing in parallel: (a) unfolding models and (b) individual response styles (RSs). To accurately understand Likert-type item responding, it is vital to parse unfolding responses from RSs. Therefore, we propose the Unfolding Item Response Tree (UIRTree) model. First, we conducted a Monte Carlo simulation study to examine the performance of the UIRTree model compared to three other models – Samejima’s Graded Response Model, Generalized Graded Unfolding Model, and Dominance Item Response Tree model, for Likert-type responses. Results showed that when data followed an unfolding response process and contained RSs, AIC was able to select the UIRTree model, while BIC was biased toward the DIRTree model in many conditions. In addition, model parameters in the UIRTree model could be accurately recovered under realistic conditions, and mis-specifying item response process or wrongly ignoring RSs was detrimental to the estimation of key parameters. Then, we used datasets from empirical studies to show that the UIRTree model could fit personality datasets well and produced more reasonable parameter estimates compared to competing models. A strong presence of RS(s) was also revealed by the UIRTree model. Finally, we provided examples with R code for UIRTree model estimation to facilitate the modeling of responses to Likert-type items in future studies.

The influence of dimensional parameters on the kinetic range of four systems of deployable structures with hinged nodes and rigid rods

In several previous studies regarding foldable structures comprised of rods and knots, it has been usual to simplify their geometry to lines and points respectively. However, this study assumes that the dimensions that these elements necessarily acquire (due to their material condition) constitute an important issue in the folding and unfolding process. To test this hypothesis, the research first defines the concept of kinetic range and its various variants and studies how variations in the radius of the rods, the eccentricity of the knots and the opening angle influence this parameter. Furthermore, this study will demonstrate that this parameter is extensible to bar bundle systems and scissors systems and finally will verify that the results obtained by using algorithm-driven models are also verifiable by mathematical methods and experimentation using physical models. As a result, the methodology followed in this article allows the inclusion of a comparative table that classifies the performance of the structural systems studied in order to establish which is the optimum in relation to their kinetic range.

General theory for localizing the where and when of entropy production meets single-molecule experiments

The laws of thermodynamics apply to biophysical systems on the nanoscale as described by the framework of stochastic thermodynamics. This theory provides universal, exact relations for quantities like work, which have been verified in experiments where a fully resolved description allows direct access to such quantities. Complementary studies consider partially hidden, coarse-grained descriptions, in which the mean entropy production typically is not directly accessible but can be bounded in terms of observable quantities. Going beyond the mean, we introduce a fluctuating entropy production that applies to individual trajectories in a coarse-grained description under time-dependent driving. Thus, this concept is applicable to the broad and experimentally significant class of driven systems in which not all relevant states can be resolved. We provide a paradigmatic example by studying an experimentally verified protein unfolding process. As a consequence, the entire distribution of the coarse-grained entropy production rather than merely its mean retains spatial and temporal information about the microscopic process. In particular, we obtain a bound on the distribution of the physical entropy production of individual unfolding events.

FACT mediates the depletion of macroH2A1.2 to expedite gene transcription

The histone variant macroH2A is generally linked to transcriptionally inactive chromatin, but how macroH2A regulates chromatin structure and functions in the transcriptional process remains elusive. This study reveals that while the integration of human macroH2A1.2 into nucleosomes does not affect their stability or folding dynamics, it notably hinders the maintenance of facilitates chromatin transcription's (FACT's) function. We show that FACT effectively diminishes the stability of macroH2A1.2-nucleosomes and expedites their depletion subsequent to the initial unfolding process. Furthermore, we identify the residue S139 in macroH2A1.2 as a critical switch to modulate FACT's function in nucleosome maintenance. Genome-wide analyses demonstrate that FACT-mediated depletion of macroH2A-nucleosomes allows the correct localization of macroH2A, while the S139 mutation reshapes macroH2A distribution and influences stimulation-induced transcription and cellular response in macrophages. Our findings provide mechanistic insights into the intricate interplay between macroH2A and FACT at the nucleosome level and elucidate their collective role in transcriptional regulation and immune response of macrophages.

Real-time gamma-ray energy spectrum / dose monitor with k-α method based on sequential bayesian estimation

Medical applications of radiation have been widely spread until now. However, the exposure of medical staff is sometimes overlooked, because treatment of patients is the first priority. The purpose of this study is to develop a small and light monitor that can measure the energy spectrum and dose of gamma-rays at the same time in real-time for medical applications. Using the monitor, the medical staff could be guided to be more aware ofthe risk of radiation, and finally the exposure to them could be substantially suppressed. So far, a CsI scintillator has been chosen as a detection device of gamma-rays and combined with a Multi-Pixel Photon Counter (MPPC) to develop a prototype monitor. Then we confirmed its basic performance with standard gamma-ray sources. To achieve the real-time measurement, α method (sequential Bayesian estimation) was adopted and improved to propose a new unfolding process, named k-α method, with which the convergence speed could really be accelerated to realize real-time measurement. Also, gamma-ray measurements with a mixed source of 133Ba, 137Cs and 60Co were carried out to confirm the validity of the present monitor. As a result, it was found that gamma-ray energy spectrum could be estimated successfully in several-tens seconds in the field of around 6 μSv/h. For the dose estimation, the correct values could be estimated just after starting measurement.

The value of direct child observation in a therapeutic parent-toddler group, for students of psychoanalysis

ABSTRACT Starting in Vienna in the 1920s, Anna Freud’s first tentative attempts at observing children became a crucial component of the ‘double approach’ which integrated direct child observation with psychoanalytic reconstruction. This approach enabled the detailed study of unfolding developmental processes and the construction of a theory of normative as well as pathological child development. Direct child observation was an integral component in the curriculum of the Psychoanalytic Master’s degree at Anna Freud’s Hampstead Clinic (later, the Anna Freud Centre) in London. The process, experience and value of observation for students of psychoanalysis is described, focussing on observers in a therapeutic parent-toddler group. The experience of observing or being observed is discussed from the perspective of staff facilitating the group, students, parents and children.

Uniform stretching behavior of single crease origami arrays

Origami arrays featuring ideal purely rotational creases inherently possess multiple kinematic degrees of freedom. The incorporation of crease rotational stiffness introduces additional constraint relations to the kinematic morphology of the origami array, due to the interaction between the plate and the crease. This paper concentrates on elucidating the coupling effect, employing two theoretical models to systematically analyze the uniform stretch process of single crease origami arrays. The validity of our theoretical approaches is substantiated through verification in the finite element method. Firstly, the mechanical equations of the origami unit, together with the length and angle constraint equations of the origami array, are amalgamated to formulate a comprehensive set of morphological computational equations specific to the single crease origami array. This set enables the realization of morphological analysis for general origami arrays. Moreover, energy equations for the origami array are computed using an equivalent rigid plate nonlinear creasing element. When combined with constraint equations corresponding to horizontal stretch displacement, these energy equations contribute to the establishment of a nonlinear optimization framework for determining the morphology of uniform single crease origami arrays. Notably, our investigation reveals that during the early stages of the unfolding process for a single crease origami array, even a small relative horizontal stretch displacement can induce a drastic change in the center crease. Through finite element analysis of general origami arrays, it is shown that the proposed theoretical analysis method applies to different crease stiffness, both unfolding and folding processes, and different plate types. The research method in this paper can provide ideas for systematically analyzing the influence mechanism of crease properties on the morphological features of origami structures.

Design Before Design: Learning to be Affected by Neurodiverse Spatial Practices

Current ethical and political revivals of design pedagogy foreground the participation of neglected subjects in attempts to democratize design practice. This article explores what participatory design practitioners in architecture might be required to learn when reconfiguring their tasks in the wake of Science and Technology Studies (STS) approaches to Participatory Things: treating them as a more-than-human assembly and unfolding process. This requires designers and architects to engage in designing the “pre-conditions” of participatory practice, “learning to be affected” by variegated actors and their peculiar ways of dwelling. In describing our attempts at approximating ourselves to the spatial practices of a neurodivergent person, we suggest this requires taking into account more-than-verbal experiences that liberal understandings of participation tend to exclude. This approach is here discussed as “design before design”: a form of design practice learning from the alternative approaches to design practice that unfolding “things” might bring to the fore and invite to explore.

Protonation-State Dependent Modulation of Hen Egg-White Lysozyme Fibrillation under the Influence of a Short Synthetic Peptide.

Under the influence of various conditions, misfolding of soluble proteins occurs, leading to the formation of toxic insoluble amyloids. The formation and deposition of such amyloids within the body are associated with detrimental biological consequences such as the onset of several amyloid-related diseases. Previously, we established a strategy for the rational design of peptide inhibitors against amyloid formation based on the amyloidogenic-prone region of the protein. In the current study, we have designed and identified an Asp-containing rationally designed hexapeptide (SqP4) as an excellent inhibitor of hen egg-white lysozyme (HEWL) amyloid progression in vitro. First, SqP4 showed strong affinity toward the native monomeric HEWL leading to the stabilization of the native form and restriction in the unfolding process of monomeric HEWL. Second, SqP4 was found to arrest the amyloidogenic misfolded structure of HEWL in a nonfibrillar monomer-like stage. We also observed the differential effect of the protonation state of the charged amino acid (Asp) within the peptide inhibitor on the amyloid formation of HEWL and explored the reason behind the observations. The findings of this study can be implemented in future strategies for the development of potent therapeutics against other amyloid-related diseases.