Ultimate Determinant Research Articles

Marx and Epistemology

ABSTRACT This article shows first that Marx, in his quest for a scientific theory of history, followed a path entirely comparable to that which Gaston Bachelard described for the sciences of nature with their epistemological ruptures. The first break is with pre-scientific knowledge. Marx outlined this break in the area of classical economics, but proceeded to deepen this rupture, leading to his first problematic. This is the one that was constructed using the famous opposition relations of production/productive forces, base/superstructure, and material life/ideological forms, that would serve as his “common thread.” The article then shows that these pairs of concepts presented several difficulties, that would lead Marx to his second, much stronger problematic. This was based on the pair of concepts “concrete” labour or useful work/ “abstract” labour or energy expenditure. These constitute the two sides of the production process, the first representing the ultimate determination and the second the main determination. The article responds to objections made concerning the generality of these concepts, and then explains how the other two oppositions are also profoundly modified. In addition, the article focuses on the Marxian conception of scientific work, which anticipates the constructivist one of Bachelard, and on the breaks that Marx made with a continuist and determinist vision of history.

A ‘translation’ perspective on socio-ecological displacement: insights from the 2014 Tokwe-Mukorsi flood in Zimbabwe

With socio-ecological displacement increasingly becoming an existential threat to many communities worldwide, there is a need for deepened understanding of salient socio-political dynamics that complicate displacement processes. Such understanding is crucial for reducing the risks associated with relocation as well as enhancing relocation management and building resilience among victims. This article utilises the concept of ‘translation’ in Actor-Network Theory (ANT) to examine the socio-political dynamics that characterised the 2014 Tokwe-Mukorsi forced displacement of over 3000 rural households in Southern Zimbabwe. Drawing on the narrations of victims in focus group discussions and of government officials (key-informants), as well as on relevant secondary data, the article engages the shifts in position by the dominant actor in the displacement and relocation processes, not to mention the imposition of new interpretations of reality, including the redefinition and distribution of roles, with a view to highlighting the ultimate determinants of resettlement outcomes. The paper found, in the main, that the power struggles between protagonists and the impact of those struggles on the relocation process, as well as the state’s dominance, ultimately exacerbated the victims’ distress.

Against Infinite Nothingness – Response to McKenzie and Adamson

AbstractIf there is something non-reducible to anything else, self-existent, unsusceptible to further explanation, then in what sense might it befundamental, and in what sense might it beunified? In my response to Kerry McKenzie and Peter Adamson, I try to clarify the idea of “foundation” that these arguments claim to show, by first contrasting two conceptions of fundamentality (a concrete complete bottom level from which the world isbuilt up –the kind people often have in mind, and an ultimate modal determination thatexplainsthings), and then discussing McKenzie’s main worry that what is modally irreducible does not necessarily qualify as fundamental, and Adamson’s worry that the bottom-level entities need not be numerically single.

Ultimate Support Pressure Determination for Shield Tunnel Faces in Saturated Strata Based on Seepage Flow Control

Existing methods for calculating the ultimate support pressure of tunnel faces do not consider the control of seepage flow. Therefore, a model for calculating the ultimate support pressure under seepage conditions was established based on a two-dimensional water head distribution model and the upper bound theorem of limit analysis. The reliability of this method was verified through comparisons with other studies. Subsequently, the influence of water level and tunnel face water pressure coefficient on stability was analyzed. The results indicate that the ultimate support pressure is linearly positively correlated with the water level and tunnel face water pressure coefficient; as the water level increases and the water pressure coefficient decreases, the failure area extends and enlarges. Finally, an existing seepage flow calculation formula was introduced, and a method for calculating the ultimate support pressure based on seepage control was proposed. The appropriate tunnel face water pressure coefficient is determined through the seepage flow calculation formula, and the corresponding ultimate support pressure is then calculated. The results demonstrate that this method can provide better theoretical guidance for seepage control in tunnel faces in practical engineering.

Descriptions of larvae of four mainly DNA barcode-matched species of chlorocyphids from south-east Asia (Odonata: Chlorocyphidae) with notes on the generic and species level larval identification of Oriental region members of the family.

The final stadium larvae of the following four species of south-east Asian Chlorocyphidae are described and compared: Aristocypha fenestrella (Rambur), Heliocypha biseriata (Selys), Libellago hyalina (Selys) and Sundacypha petiolata (Selys), including both sexes for the latter two species. Excepting one L. hyalina specimen from Brunei, identified by supposition based on habitat, all specimens were identified by comparing and matching the mitochondrial marker COI with that of known adult specimens from Sarawak, Brunei and several localities throughout tropical Asia. The specimens presented close matches with all adults in this gene. An assessment of the efficacy of this method of identification is provided, noting that in some cases close species cannot be separated by bar-code matching and ultimate determination is partially based on known distributions of adults. Some aspects of the relationships among genera revealed by the genetic analyses are also discussed. In addition, an exuvia of Libellago lineata (Burmeister) from northern Thailand, identified by supposition, is partially described for the purpose of comparison with L. hyalina. For the morphological analysis the unique features of chlorocyphid anatomy are discussed, and some new terminology is introduced. Overall, the morphological analysis revealed numerous clear differences between the four species studied, and comparisons with available literature suggest that some of these may be characteristic of their genera. It is also evident that in some cases clear interspecific differences occur within genera. It is however concluded that a generic level larval key for the Oriental region Chlorocyphidae based on morphology may never be attainable, although local generic or even species level keys addressing the fauna of limited geographic areas may be possible in many places, especially as the larvae of more species come to be known and described in detail.

Evolution of Litter Size: Proximate and Ultimate Mechanisms.

Relative reproductive success and failure are the ultimate determinants of Darwinian fitness. As such, reproductive traits and variations therein have an immediate and considerable impact on the evolutionary trajectory of lineages. Historically, significant attention has been paid to the ecological and evolutionary processes (ultimate factors) that shape the diversity and canalization of reproductive traits within groups to better our understanding of organismal diversity and population or species resilience. In contrast, the physiological systems that mediate variation within and among species (i.e., the proximate factors) in reproductive traits remain a significant black box. To date, there is comparatively little information about how proximate mechanisms constrain or promote evolutionary potential in reproductive traits. In this mini-review, we focus on litter size in Eutherian mammals as a trait with relatively well-defined diversity (litter sizes are well-described both within and across species) and for which some genetic determinants have been identified. We discuss both the ultimate and potential proximate determinants of litter size with special attention to the breadth of physiological traits that may act as "toggle" switches for evolution of litter size. We close with a brief discussion of the role that physiological plasticity may play in the evolution of litter size and lay out several forward-looking areas for future research.

Top-Heavy CapsNets Based on Spatiotemporal Non-Local for Action Recognition

To effectively comprehend human actions, we have developed a Deep Neural Network (DNN) that utilizes inner spatiotemporal non-locality to capture meaningful semantic context for efficient action identification. This work introduces the Top-Heavy CapsNet as a novel approach for video analysis, incorporating a 3D Convolutional Neural Network (3DCNN) to apply the thematic actions of local classifiers for effective classification based on motion from the spatiotemporal context in videos. This DNN comprises multiple layers, including 3D Convolutional Neural Network (3DCNN), Spatial Depth-Based Non-Local (SBN) layer, and Deep Capsule (DCapsNet). Firstly, the 3DCNN extracts structured and semantic information from RGB and optical flow streams. Secondly, the SBN layer processes feature blocks with spatial depth to emphasize visually advantageous cues, potentially aiding in action differentiation. Finally, DCapsNet is more effective in exploiting vectorized prominent features to represent objects and various action features for the ultimate label determination. Experimental results demonstrate that the proposed DNN achieves an average accuracy of 97.6%, surpassing conventional DNNs on the traffic police dataset. Furthermore, the proposed DNN attains average accuracies of 98.3% and 80.7% on the UCF101 and HMDB51 datasets, respectively. This underscores the applicability of the proposed DNN for effectively recognizing diverse actions performed by subjects in videos.

Advanced medical imaging for forensic triage: A study of the added value of combining PMCT and PMMR of the head

BackgroundApproximately 170,000 individuals die annually in the Netherlands. Dutch law mandates examinations to distinguish between natural death and unnatural death. Traditionally, this involves external examinations and an inspection of medical records; however, medical imaging has emerged as a tool for investigating deaths. ObjectiveThe objective of the study was to investigate whether the addition of post-mortem magnetic resonance (PMMR) to post-mortem computed tomography (PMCT) could assist in the categorisation of deaths as natural or unnatural and augment confidence in those classifications. MethodsIn this retrospective study, the PMCT and PMMR head images of 50 individuals were evaluated by a forensic radiologist. The impact of PMMR on lesion detection, the cause of death (COD), the differentiation between natural death and unnatural death, and confidence levels were assessed. All available case information was used as the reference standard. ResultsThe addition of the PMMR led to a statistically significant increase in lesion detection (48%), changes in the classification of COD in four cases, and an increased level of confidence in the classification. Differentiation between natural death and unnatural death reversed in 10 cases, altering the overall manner of death (MOD) classification in 20% of cases. ConclusionWhen PMCT indicates a natural or unnatural death, PMMR is unnecessary. PMMR of the head is recommended in situations in which the MOD is uncertain based on PMCT findings. The ultimate determination of a natural death and unnatural death should always take into account the results of external examinations, police investigations, and other available information.

Weak coupling between energetic status and the timing of reproduction in an Arctic ungulate

Bioenergetic constraints are the ultimate determinant of the timing of reproduction, and seasonal breeding is consequently a widely observed trait. Consistent with this, attention has focused on plasticity in reproductive phenology conceptualized as a response to concomitant advances in the phenology of the environmental energy supply caused by climate change. Few studies, however, have directly compared timing of reproduction with energetic status in free-living wild animals. Here we demonstrate that neither body mass nor adiposity are strong proximate predictors of date of conception in wild reindeer (Rangifer tarandus). Weak coupling between energetic status and the phenology of reproduction accounts for the increasing discrepancy between the phenology of forage (energy supply) and the phenology of reproduction (energy demand) observed across the last 2–4 decades in two populations of this species. The results emphasise that phenological plasticity is not a passive response to changes in energy supply but derives from the way in which environmental factors interact with the core control mechanisms that govern timing. Central in this respect is integration, within the rheostatic centres of the hypothalamus, of information on nutritional status with the circannual life-history calendar.

Anthrax Vaccines in the 21st Century.

Vaccination against Bacillus anthracis is the best preventive measure against the development of deadly anthrax disease in the event of exposure to anthrax either as a bioweapon or in its naturally occurring form. Anthrax vaccines, however, have historically been plagued with controversy, particularly related to their safety. Fortunately, recent improvements in anthrax vaccines have been shown to confer protection with reduced short-term safety concerns, although questions about long-term safety remain. Here, we (a) review recent and ongoing advances in anthrax vaccine development, (b) emphasize the need for thorough characterization of current (and future) vaccines, (c) bring to focus the importance of host immunogenetics as the ultimate determinant of successful antibody production and protection, and (d) discuss the need for the systematic, active, and targeted monitoring of vaccine recipients for possible Chronic Multisymptom Illness (CMI).

Phase-field simulations of the effect of temperature and interface for zirconium δ-hydrides

Hydride precipitation in zirconium cladding materials can damage their integrity and durability. Service temperature and material defects have a significant effect on the dynamic growth of hydrides. In this study, we have developed a phase-field model based on the assumption of elastic behaviour within a specific temperature range (613 K–653 K). This model allows us to study the influence of temperature and interfacial effects on the morphology, stress, and average growth rate of zirconium hydride. The results suggest that changes in temperature and interfacial energy influence the length-to-thickness ratio and average growth rate of the hydride morphology. The ultimate determinant of hydride orientation is the loss of interfacial coherency, primarily induced by interfacial dislocation defects and quantifiable by the mismatch degree q. An escalation in interfacial coherency loss leads to a transition of hydride growth from horizontal to vertical, accompanied by the onset of redirection behaviour. Interestingly, redirection occurs at a critical mismatch level, denoted as q c, and remains unaffected by variations in temperature and interfacial energy. However, this redirection leads to an increase in the maximum stress, which may influence the direction of hydride crack propagation. This research highlights the importance of interfacial coherency and provides valuable insights into the morphology and growth kinetics of hydrides in zirconium alloys.

SmFRET-assisted RNA structure prediction.

Single-molecule Förster Resonance Energy Transfer (smFRET) is a powerful biophysical technique that utilizes the distance-dependent energy transfer between donor and acceptor dyes linked to individual molecules, providing insights into molecular conformational changes and interactions at the single-molecule level. Prior investigations leveraged smFRET to study the conformational dynamics of single truncated Ubc4 pre-mRNA molecules during splicing, yet these efforts did not prioritize structural modeling. In this study, we develop an smFRET-assisted RNA prediction method to predict the 2D and 3D structures of this pre-mRNA. To achieve this, we initiate the process by generating RNA structural ensembles through coarse-grained molecular dynamics (MD) simulations. Subsequently, inter-dye distances are calculated for these RNA structural ensembles by performing all-atom MD simulations of the dye groups. The ultimate determination of the 2D and 3D structures for the pre-mRNA is achieved by comparing the calculated inter-dye distances with experimental counterparts. Notably, our computational results demonstrate a significant alignment with experimental findings, which involve a conformational change at the 2D level.

PEREGRINATIONS ON THE STUDY OF THE OPTICAL PROPERTIES OF NONSPHERICAL PARTICLES

PEREGRINATIONS ON THE STUDY OF THE OPTICAL PROPERTIES OF NONSPHERICAL PARTICLES

Ultimate Fate and Determination of Pyriproxyfen and Fenpropathrin in the Environment: A Critical Review

Since the 1990s, the insect growth regulator pyriproxyfen and pyrethroids such as fenpropathrin have been widely used to reduce pest populations in agriculture. The widespread use of these insecticides makes it essential for researchers to understand how they behave in terrestrial ecosystems and how they can be detected. This work reviewed the most effective analytical techniques used to detect pyriproxyfen and fenpropathrin in various samples. The degradation of pyriproxyfen and fenpropathrin in soil takes time, but in aerobic environments, pyriproxyfen and fenpropathrin are degraded rapidly following first-order kinetics or pseudo-first-order kinetics. Both insecticides tend to adsorb on soils and are not susceptible to leaching into groundwater. Based on greenhouse or field conditions, both insecticides degrade differently by following first-order kinetics, and their half-lives in plants range from one to three weeks. Since both insecticide residues are soluble in acetone, hexane, ethyl acetate, and acetonitrile, they can be extracted in those solvents. They can also be processed in a variety of ways discussed in this paper. Ultimately, the review explains how fate profiles of pyriproxyfen and fenpropathrin in soil and plants affect these molecules' adverse effects on non-target organisms.

Pharmacological hallmarks of allostery at the M4 muscarinic receptor elucidated through structure and dynamics.

Allosteric modulation of G protein-coupled receptors (GPCRs) is a major paradigm in drug discovery. Despite decades of research, a molecular-level understanding of the general principles that govern the myriad pharmacological effects exerted by GPCR allosteric modulators remains limited. The M4 muscarinic acetylcholine receptor (M4 mAChR) is a validated and clinically relevant allosteric drug target for several major psychiatric and cognitive disorders. In this study, we rigorously quantified the affinity, efficacy, and magnitude of modulation of two different positive allosteric modulators, LY2033298 (LY298) and VU0467154 (VU154), combined with the endogenous agonist acetylcholine (ACh) or the high-affinity agonist iperoxo (Ipx), at the human M4 mAChR. By determining the cryo-electron microscopy structures of the M4 mAChR, bound to a cognate Gi1 protein and in complex with ACh, Ipx, LY298-Ipx, and VU154-Ipx, and applying molecular dynamics simulations, we determine key molecular mechanisms underlying allosteric pharmacology. In addition to delineating the contribution of spatially distinct binding sites on observed pharmacology, our findings also revealed a vital role for orthosteric and allosteric ligand-receptor-transducer complex stability, mediated by conformational dynamics between these sites, in the ultimate determination of affinity, efficacy, cooperativity, probe dependence, and species variability. There results provide a holistic framework for further GPCR mechanistic studies and can aid in the discovery and design of future allosteric drugs.

Molecular Insights on Morphology, Composition, and Stability of Mixed Micelles Formed by Ionic Surfactant and Nonionic Block Copolymer in Water Using Coarse-Grained Molecular Dynamics Simulations.

The nanoscale association domains are the ultimate determinants of the macroscopic properties of complex fluids involving amphiphilic polymers and surfactants, and hence, it is foremost important to understand the role of polymer/surfactant concentration on these domains. We have used coarse-grained molecular dynamics simulations to investigate the effect of polymer/surfactant concentration on the morphology of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, i.e., pluronics or poloxamers) block copolymer, and ionic surfactants sodium dodecyl sulfate (SDS), mixed micelles in aqueous solution. The proclivity of the surfactant to form the mixed micelles is also probed using umbrella sampling simulations. In this study, we observed that the core of the pluronic + SDS formed mixed micelles consists of PPO, the alkyl tail of SDS, and some water molecules, whereas the PEO, water, and sulfate headgroups of SDS form a shell, consistent with experimental observations. The micelles are spherical at high-pluronic/low-SDS compositions, ellipsoidal at high-SDS/low-pluronic compositions, and wormlike-cylindrical at high-pluronic/high-SDS compositions. The transitions in micelle morphology are governed by the solvent accessible surface area of mixed aggregates, electrostatic repulsion between SDS-headgroups, and dehydration of PEO and PPO segments. The free energy barrier for SDS escape is much higher in mixed micelles than in pure SDS micelles, indicating a stronger tendency for SDS to form pluronic-SDS mixed micelles.

Increased birth rank of homosexual males: disentangling the older brother effect and sexual antagonism hypothesis

Male homosexual orientation remains a Darwinian paradox, as there is no consensus on its evolutionary (ultimate) determinants. One intriguing feature of homosexual men is their higher male birth rank compared to heterosexual men. This can be explained by two non-exclusive mechanisms: an antagonistic effect (AE), implying that more fertile women have a higher chance of having a homosexual son and to produce children with a higher mean birth rank, or a fraternal birth effect (FBOE), where each additional older brother increases the chances for a male embryo to develop a homosexual orientation due to an immunoreactivity process. However, there is no consensus on whether both FBOE and AE are present in human populations, or if only one of these mechanisms is at play with its effect mimicking the signature of the other mechanism. An additional sororal birth order effect (SBOE) has also recently been proposed. To clarify this situation, we developed theoretical and statistical tools to study FBOE and AE independently or in combination, taking into account all known sampling biases. These tools were applied on new individual data, and on various available published data (two individual datasets, and all relevant aggregated data). Support for FBOE was apparent in aggregated data, with the FBOE increasing linearly with fertility. The FBOE was also supported in two individual datasets. An SBOE is generated when sampling in presence of FBOE, suggesting that controlling for FBOE is required to avoid artefactual SBOE. AE was not supported in individual datasets, including the analysis of the extended maternal family. The evolutionary implications of these findings are discussed.

The role of B-type lamins in genome architecture, chromatin dynamics, and gene regulation.

Chromatin is hierarchically organized in a dynamic manner in the mammalian cell nucleus, but the causal relationship between physical 3D genome organization and transcriptional activity and genome activity remains to be fully understood. Genome-wide studies have suggested that the interplay of several principles leads to the emergence of the major organizational features of the genome, including polymer-polymer interactions, chromatin loop extrusion, phase separation, the physical interaction of chromatin with stable architectural elements of the nucleus (i.e., nuclear envelope), and chromatin dynamics. The nuclear lamina is the ultimate determinant of nuclear space that posits a structural limit on the 3D genome organization. Lamins are structural components of the nuclear lamina that provide mechanical support to the nucleus and regulate genome organization and transcription. However, identifying the direct roles of lamins on dynamic genome organization has been challenging as depletion of lamin proteins severely impacts cell viability. To overcome this challenge, we engineered colon carcinoma cells to rapidly and completely degrade endogenous B-type lamins using Auxin-induced degron (AID) technology. We utilized a suite of novel technologies such as live-cell Dual Partial Wave Spectroscopic (Dual-PWS) microscopy, in situ Hi-C, and CRISPR-Sirius to demonstrate that acute lamin depletion increases chromatin dynamics at the nuclear periphery and weakens chromatin compartmentalization, as well as physically repositions gene-specific loci with respect to the nuclear periphery. Further, using the reversible AID system, we show that significantly altered genes after acute lamin depletion are enriched near LADs, and replenishment of lamins re-establishes their basal expression. Our findings provide a deeper understanding of the role B-type lamins in cell type-specific 3D genome organization and transcription.

The challenging surgical vascular access creation.

With the increasing life expectancy of patients with end-stage kidney disease, the creation and maintenance of hemodialysis vascular access are becoming more challenging. A comprehensive patient evaluation including a complete history, physical examination, and ultrasonographic vessel assessment is the foundation of the clinical evaluation. A patient-centered approach acknowledges the myriad of factors that impact the selection of optimal access for the distinct clinical and social circumstance of each patient. An interdisciplinary team approach involving various healthcare providers in all stages of hemodialysis access creation is important and associated with better outcomes. While patency is considered the most important parameter in most vascular reconstructive scenarios, the ultimate determinant of success in vascular access for hemodialysis is a circuit that allows consistent and uninterrupted delivery of the prescribed hemodialysis. The best conduit is one that is superficial, easily identified, straight, and of a large caliber. Individual patient factors and skill level of the cannulating technician also play a crucial role in the initial success and maintenance of vascular access. Special attention should be considered in dealing with more challenging groups such as the elderly population where the newest vascular access guidance from The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative will be transformative. The current guidelines recommend monitoring the vascular access by regular physical and clinical assessments, however, inadequate evidence is available to support routine ultrasonographic surveillance for improving access patency.

Deficiency of transcription factor Nkx6.1 does not prevent insulin secretion in INS-1E cells

Pancreatic-β-cell-specifying transcription factor Nkx6.1, indispensable for embryonic development of the pancreatic epithelium and commitment to β-cell lineage, directly controls the expression of a glucose transporter (Glut2), pyruvate carboxylase (Pcx), and genes for insulin processing (endoplasmic reticulum oxidoreductase-1β, Ero1lb; zinc transporter-8, Slc30a8). The Nkx6.1 decline in aging diabetic Goto-Kakizaki rats contributes to β-cell trans-differentiation into δ-cells. Elucidating further Nkx6.1 roles, we studied Nkx6.1 ablation in rat INS-1E cells, prepared by CRISPR/Cas9 gene editing from single colonies. INS-1ENkx6.1–/– cells exhibited unchanged glucose-stimulated insulin secretion (GSIS), moderately decreased phosphorylating/non-phosphorylating respiration ratios at high glucose; unchanged but delayed ATP-elevation responses to glucose; delayed uptake of fluorescent glucose analog, but slightly improved cytosolic Ca2+-oscillations, induced by glucose; despite approximately halved Glut2, Pcx, Ero1lb, and Slc30a8 expression, and reduced nuclear receptors Nr4a1 and Nr4a3. Thus, ATP synthesis was time-compensated, despite the delayed GLUT2-mediated glucose uptake and crippled pyruvate-malate redox shuttle (owing to the PCX-deficiency) in INS-1ENkx6.1–/– cells. Nkx6.1 thus controls the expression of genes that are not essential for acute insulin secretion, the function of which can be compensated for. Considerations that Nkx6.1 deficiency is an ultimate determinant of β-cell pathology beyond cell trans-(de-)differentiation or β-cell identity are not supported by our results.