Counterintuitive Role Research Articles

Night cooling by hybrid supply ventilation – analytical predictions of airflow rates and the ‘hybrid ventilation triangles’

Overheating in buildings can be mitigated during periods of excessively warm weather through the application of a night purge ventilation strategy. Building on the mathematical model of Waterson and Hunt (2024), we investigate the emerging field of hybrid ventilation – specifically the rates of airflow achieved by the simultaneous combination of ‘stack-driven’ natural displacement ventilation and a mechanical supply. Whilst the focus of Waterson and Hunt (2024) was specifically on predicting the time taken to complete a purge, herein we focus on airflow rates and in doing so elucidate the somewhat counter intuitive role that the mechanical supply has on the natural ventilation flow rates. Our results challenge the perception that a hybrid approach must be superior to both solely natural and mechanical strategies. Focusing on the variation in airflow rates during a hybrid purge, our model reveals: (i) a hybrid purge offers an improvement over a solely mechanical purge only during one of the two distinct flow regimes identified; and (ii) the manner in which the stack-driven and mechanical components combine is highly nuanced and cannot be predicted by the linear superposition of the constituent stack-driven and mechanical contributions.

KAP1 negatively regulates RNA polymerase II elongation kinetics to activate signal-induced transcription

Signal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction remain poorly understood. By combining an acute depletion system with several genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Acute KAP1 loss triggers an increase in RNA polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation thereby dampening IEGs transcriptional output. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions.

Actin-organizing protein palladin modulates C2C12 cell fate determination

BackgroundCell confluency and serum deprivation promote the transition of C2C12 myoblasts into myocytes and subsequence fusion into myotubes. However, despite all myoblasts undergoing the same serum deprivation trigger, their responses vary: whether they become founder myocytes, remain proliferative, or evolve into fusion-competent myocytes remains unclear. We have previously shown that depletion of the scaffolding protein palladin in myoblasts inhibits cell migration and promotes premature muscle differentiation, pointing to its potential significance in muscle development and the necessity for a more in-depth examination of its function in cellular heterogeneity. Methods and resultsHere, we showed that the subcellular localization of palladin might contribute to founder-fate cell decision in the early differentiation process. Depleting palladin in C2C12 myoblasts depleted integrin-β3 plasma membrane localization of and focal adhesion formation at the early stage of myogenesis, decreased kindlin-2 and metavinculin expression during the myotube maturation process, leading to the inability of myocytes to fuse into preexisting mature myotubes. This aligns with previous findings where early differentiation into nascent myotubes occurred but compromised maturation. In contrast, wildtype C2C12 overexpressing the 140-kDa palladin isoform developed a polarized morphology with star-like structures toward other myoblasts. However, this behaviour was not observed in palladin-depleted cells, where the 140-kDa palladin overexpression could not recover cell migration capacity, suggesting other palladin isoforms are also needed to establish cell polarity. ConclusionOur study identifies a counter-intuitive role for palladin in regulating myoblast-to-myocyte cell fate decisions and impacting their ability to form mature multinucleated myotubes by influencing cell signalling pathways and cytoskeletal organization, necessary for skeletal muscle regeneration and repair studies.

Harnessing Multistep Chalcogen Bonding Activation in the α-Stereoselective Synthesis of Iminoglycosides.

The use of noncovalent interactions (NCIs) has received significant attention as a pivotal synthetic handle. Recently, the exploitation of unconventional NCIs has gained considerable traction in challenging reaction manifolds such as glycosylation due to their capacity to facilitate entry into difficult-to-access sugars and glycomimetics. While investigations involving oxacyclic pyrano- or furanoside scaffolds are relatively common, methods that allow the selective synthesis of biologically important iminosugars are comparatively rare. Here, we report the capacity of a phosphonochalcogenide (PCH) to catalyze the stereoselective α-iminoglycosylation of iminoglycals with a wide array of glycosyl acceptors with remarkable protecting group tolerance. Mechanistic studies have illuminated the counterintuitive role of the catalyst in serially activating both the glycosyl donor and acceptor in the up/downstream stages of the reaction through chalcogen bonding (ChB). The dynamic interaction of chalcogens with substrates opens up new mechanistic opportunities based on iterative ChB catalyst engagement and disengagement in multiple elementary steps.

Inverting the paradigm: digital transformation’s impact on firm performance and the counterintuitive role of gender

Purpose This study aims to analyze the impact of digital transformation on firm performance within the banking sector, specifically focusing on the Amman Stock Exchange (ASE)-listed banks from 2015 to 2022. Additionally, it explores the influence of gender dynamics on the implementation and outcomes of these digital transformation initiatives. Design/methodology/approach The study adopts a robust empirical approach, using manual content analysis of annual reports from ASE-listed banks. The Digital Transformation Disclosure Index (DTDI) is used to assess the extent and nature of digital transformation initiatives within these banks. The methodology is designed to provide a comprehensive evaluation of the correlation between digital transformation efforts, firm performance and gender dynamics. Findings The research reveals that digital transformation initiatives have a significant positive impact on the performance of ASE-listed banks. It also uncovers nuanced insights into the role of gender dynamics, indicating that gender diversity within firms influences the adoption and success of digital transformation strategies in complex ways. Research limitations/implications The findings of this study contribute to the understanding of digital transformation in the banking sector, offering empirical evidence on its benefits for firm performance. Additionally, the study illuminates the intricate role of gender dynamics in digital transformation, providing a new perspective on organizational diversity within the context of technological change. Originality/value This research pioneers in academically linking digital transformation and gender dynamics within the banking sector, addressing a notable gap and introducing a fresh academic perspective. Practically, it equips banking executives and policymakers with actionable insights for gender-inclusive digital strategies, crucial for enhanced firm performance. Methodologically, the study sets a benchmark in research innovation, using the DTDI to offer a replicable model for future investigations in this evolving field.

Cooperativity and Frustration Effects (or Lack Thereof) in Polarizable and Non-polarizable Force Fields.

Understanding cooperativity and frustration is crucial for studying biological processes such as molecular recognition and protein aggregation. Force fields have been extensively utilized to explore cooperativity in the formation of protein secondary structures and self-assembled systems. Multiple studies have demonstrated that polarizable force fields provide more accurate descriptions of this phenomenon compared to fixed-charge pairwise nonpolarizable force fields, thanks to the incorporation of polarization effects. In this study, we assess the performance of the AMOEBA polarizable force field and the AMBER and OPLS nonpolarizable pairwise force fields in capturing positive and negative cooperativity recently explored in neutral and charged molecular clusters using density functional theory. Our findings show that polarizable and nonpolarizable force fields qualitatively reproduce the relative cooperativity observed in electron structure calculations. However, AMBER and OPLS fail to describe absolute cooperativity. In contrast, AMOEBA accounts for the absolute cooperativity by considering interactions beyond pairwise interactions. According to the energy decomposition analysis, it is observed that the electrostatic interactions calculated with the AMBER and OPLS force fields seem to play an important and counterintuitive role in reproducing the adiabatic interaction energies calculated with density functional theory. However, it is important to note that these force fields, due to their nature, do not explicitly incorporate many-body effects, which limits their ability to accurately describe cooperativity. On the other hand, frustration in polarizable and nonpolarizable force fields is caused by changes in bond stretching and angle bending terms of the building blocks when they are forming a complex.

The counterintuitive role of efficiency: implications for the ecological impact of health care

Health systems must decarbonise and, in rich nations, degrow their overall ecological impact if they are to operate within ecological limits.1,2 This imperative has inspired a range of policies and practices for sustainable health care, including those focused on efficiency, defined here as measures that seek to deliver an equivalent service using fewer inputs.1 In health care, as in other sectors, efficiency measures are attractive for several reasons: they appear to avoid tradeoffs between the interests of patients, the environment, and health system funders; their benefits can be quantified in formats familiar to decision makers; an they are premised on providing the same care that people have come to expect.

Mesoscopic architecture enhances communication across the macaque connectome revealing structure-function correspondence in the brain.

Analyzing the brain in terms of organizational structures at intermediate scales provides an approach to unravel the complexity arising from interactions between its large number of components. Focusing on a wiring diagram that spans the cortex, basal ganglia, and thalamus of the macaque brain, we identify robust modules in the network that provide a mesoscopic-level description of its topological architecture. Surprisingly, we find that the modular architecture facilitates rapid communication across the network, instead of localizing activity as is typically expected in networks having community organization. By considering processes of diffusive spreading and coordination, we demonstrate that the specific pattern of inter- and intramodular connectivity in the network allows propagation to be even faster than equivalent randomized networks with or without modular structure. This pattern of connectivity is seen at different scales and is conserved across principal cortical divisions, as well as subcortical structures. Furthermore, we find that the physical proximity between areas is insufficient to explain the modular organization, as similar mesoscopic structures can be obtained even after factoring out the effect of distance constraints on the connectivity. By supplementing the topological information about the macaque connectome with physical locations, volumes, and functions of the constituent areas and analyzing this augmented dataset, we reveal a counterintuitive role played by the modular architecture of the brain in promoting global coordination of its activity. It suggests a possible explanation for the ubiquity of modularity in brain networks.

Cascade Assembly of Bridged N-Substituted Azaozonides: The Counterintuitive Role of Nitrogen Source Nucleophilicity

Counterintuitively, the low basicity of the NH2 group in hydrazides makes them preferred nucleophiles for the synthesis of the N-substituted azaozonides in acid-catalyzed three-component condensation with 1,5-diketones and H2O2. In the case of more basic N sources, e.g., hydrazine and primary amines, such condensation does not occur under these reaction conditions. The method can be applied to a wide range of hydrazides and affords the target bicyclic azaozonides in 27-86% yields.

Palladium-Catalyzed trans-Hydroalkoxylation: Counterintuitive Use of an Aryl Iodide Additive to Promote C-H Bond Formation.

We report an enantioselective palladium-catalyzed trans-hydroalkoxylation of propargylic amines with a trifluoroacetaldehyde-derived tether to build chiral oxazolidines. Diastereoselective hydrogenation using a heterogeneous palladium catalyst then gave access to protected benzylic amino alcohols in 45–87% yields and 84–94% ee values. Hydroalkoxylation of the alkynes required a catalytic amount of aryl iodide, highlighting the counterintuitive key role played by a putative Pd(II)/ArI oxidative addition complex to promote oxypalladation/protodemetalation.

The Pathogenic Roles of IL-22 in Colitis: Its Transcription Regulation by Musculin in T Helper Subsets and Innate Lymphoid Cells

IL-22 plays a crucial role in promoting inflammation, antimicrobial immunity and tissue repair at barrier surfaces. The role of IL-22 in colitis is still controversial: while IL-22 has a protective effect on gut epithelium in acute injuries, it also enhances colitis in a context-dependent manner. Here, we summarize the Yin and Yang of IL-22 in colitis. Particularly, we emphasize the role of innate lymphoid cells (ILCs) in IL-22 production and regulation. A previously underappreciated transcription factor, Musculin (MSC), has been recently identified to be expressed in not only Th17 cells, but also RORγt+/Id2+ IL-22-producing group 3 ILCs in the gut of naïve mice. We hypothesize that the co-expression and interaction of MSC with the key transcription repressor Id2 in developing lymphoid cells (e.g., in LTi cells) and ILC precursors might fine tune the developmental programs or regulate the plasticity of adaptive Th subset and innate ILCs. The much-elevated expression of IL-22 in MSC-/- ILC3s suggests that MSC may function as: 1) a transcription suppressor for cytokines, particularly for IL-22, and/or 2) a gatekeeper for specific lineages of Th cells and innate ILCs as well. Amelioration of colitis symptoms in MSC-/- mice by IL-22-blocking agent IL-22BP-Fc suggests a counterintuitive pathogenic role of IL-22 in the absence of MSC as a checkpoint. The theory that exuberant production of IL-22 under pathological conditions (e.g., in human inflammatory bowel disease, IBD) may cause epithelial inflammation due to endoplasmic reticulum (ER) stress response is worth further investigation. Rheostatic regulation of IL-22 may be of therapeutic value to restore homeostatic balance and promote intestinal health in human colitis.

COVID-19 epidemic and mitigation policies: Positive and normative analyses in a neoclassical growth model.

The COVID‐19 pandemic is still ravaging the planet, but its (short‐, medium‐, and long‐term) diverse effects on health, economy, and society are far from being understood. This article investigates the potential impact of a deadly epidemic and its main nonpharmaceutical control interventions (social distancing vs. testing–tracing–isolation, TTI) on capital accumulation and economic development at different time scales. This is done by integrating an epidemiological susceptible–infectious–recovered model with a Solow‐type growth model including public expenditure, as a parsimonious setting to offer insights on the trade‐off between protecting human lives and the economy and society. The work clarifies (i) the long‐term interactions amongst a deadly infection, demography, and capital accumulation, (ii) the lack of viability of persistent social distancing measures also using an analytical characterization, and the threat of policy‐enhanced COVID‐19 endemicity, (iii) the potentially high return on investments in TTI activities to avoid future lockdowns and related capital disruption. It also quantifies the welfare effects of a range of policies, confirming a counterintuitive role for tax‐funded preventive investments aimed at strengthening TTI as more desirable interventions than generalized lockdowns.

Heralding on the detection of zero photons

Although heralding signals in quantum optics experiments are typically based on the detection of exactly one photon, it has recently been theoretically shown that heralding based on the detection of zero photons can be useful in a number of quantum information applications. Here we describe an experimental technique for "heralding on zero photons" using conventional single-photon detectors and time-tagging methods. We find that detector efficiency and dark count rates play a counterintuitive role in the ability to accurately detect zero photons, and demonstrate these effects in an experiment that involves heralding on zero photons in the well-known Hong-Ou-Mandel interferometer.

Enhanced work hardening from oxygen-stabilized ω precipitates in an aged metastable β Ti-Nb alloy

High levels of oxygen in solid solution in Ti alloys are considered detrimental to mechanical properties because of embrittlement concerns. In metastable β titanium alloys, the formation of isothermal ω precipitates is also known to cause severe embrittlement and ductility reduction. However, oxygen has been shown to partition to the ω phase during ageing, and this partitioning behavior may potentially impact ω’s mechanical contribution. Using micropillar compression, we compared the deformation behavior of Ti-20Nb (at. %) with oxygen-stabilized ω precipitates to the behavior of oxygen-free specimens. The oxygen-stabilized microstructures showed increased compressive yield strength and enhanced work hardening behavior compared to oxygen-free specimens. In the absence of oxygen, the compressed pillars showed slip band formation and catastrophic failure, and transmission electron microscopy imaging revealed that ω precipitates were sheared within the continuous deformation channels resulting in slip localization. In contrast, oxygen-stabilized ω precipitates were harder to shear and the formation of continuous deformation channels was suppressed during compression, leading to improved work hardening behavior up to 15% strain. This counter-intuitive role of oxygen may offer design strategies to address the significant embrittlement and loss of ductility observed for ω-strengthened β Ti alloys without oxygen and avenues to expand the use of β Ti alloys.

Plumbing the depths of the graphene wetting controversy

Plumbing the depths of the graphene wetting controversy

Beyond the Classical Contributions to Exchange Coupling in Binuclear Transition Metal Complexes.

Complexes with two or more magnetically coupled metal ions have attracted considerable attention as catalysts of many vital processes, single-molecule magnets, or spin-crossover compounds. Elucidation of their electronic structures is essential for understanding their catalytic and magnetic properties. Here, we provide an unprecedented insight into exchange-coupling mechanisms between the magnetic centers in six prototypical bis-μ-oxo bimetallic M2O2 complexes, including two biologically relevant models of non-heme iron enzymes. Employing multiconfigurational/multireference methods and related orbital entanglement analysis, we revealed the essential and counterintuitive role of predominantly unoccupied valence metal d orbitals in their strong antiferromagnetic coupling. We found that the participation of these orbitals is twofold. First, they enhance the superexchange between the singly occupied d orbitals. Second, they become substantially occupied and thus directly magnetically active, which we perceive as a new mechanism of the exchange interaction between the magnetic transition metal centers.

Correction: Hypoxia-Inducible Factor α Subunits Regulate Tie2-Expressing Macrophages That Influence Tumor Oxygen and Perfusion in Murine Breast Cancer.

Tie2-expressing monocytes/macrophages (TEMs) are a distinct subset of proangiogenic monocytes selectively recruited to tumors in breast cancer. Because of the hypoxic nature of solid tumors, we investigated if oxygen, via hypoxia-inducible transcription factors HIF-1α and HIF-2α, regulates TEM function in the hypoxic tumor microenvironment. We orthotopically implanted PyMT breast tumor cells into the mammary fat pads of syngeneic LysMcre, HIF-1α fl/fl /LysMcre, or HIF-2α fl/fl /LysMcre mice and evaluated the tumor TEM population. There was no difference in the percentage of tumor macrophages among the mouse groups. In contrast, HIF-1α fl/fl /LysMcre mice had a significantly smaller percentage of tumor TEMs compared with control and HIF-2α fl/fl /LysMcre mice. Proangiogenic TEMs in macrophage HIF-2α-deficient tumors presented significantly more CD31+ microvessel density but exacerbated hypoxia and tissue necrosis. Reduced numbers of proangiogenic TEMs in macrophage HIF-1α-deficient tumors presented significantly less microvessel density but tumor vessels that were more functional as lectin injection revealed more perfusion, and functional electron paramagnetic resonance analysis revealed more oxygen in those tumors. Macrophage HIF-1α-deficient tumors also responded significantly to chemotherapy. These data introduce a previously undescribed and counterintuitive prohypoxia role for proangiogenic TEMs in breast cancer which is, in part, suppressed by HIF-2α.

Hypoxia-Inducible Factor α Subunits Regulate Tie2-Expressing Macrophages That Influence Tumor Oxygen and Perfusion in Murine Breast Cancer.

Tie2-expressing monocytes/macrophages (TEMs) are a distinct subset of proangiogenic monocytes selectively recruited to tumors in breast cancer. Because of the hypoxic nature of solid tumors, we investigated if oxygen, via hypoxia-inducible transcription factors HIF-1α and HIF-2α, regulates TEM function in the hypoxic tumor microenvironment. We orthotopically implanted PyMT breast tumor cells into the mammary fat pads of syngeneic LysMcre, HIF-1α fl/fl /LysMcre, or HIF-2α fl/fl /LysMcre mice and evaluated the tumor TEM population. There was no difference in the percentage of tumor macrophages among the mouse groups. In contrast, HIF-1α fl/fl /LysMcre mice had a significantly smaller percentage of tumor TEMs compared with control and HIF-2α fl/fl /LysMcre mice. Proangiogenic TEMs in macrophage HIF-2α-deficient tumors presented significantly more CD31+ microvessel density but exacerbated hypoxia and tissue necrosis. Reduced numbers of proangiogenic TEMs in macrophage HIF-1α-deficient tumors presented significantly less microvessel density but tumor vessels that were more functional as lectin injection revealed more perfusion, and functional electron paramagnetic resonance analysis revealed more oxygen in those tumors. Macrophage HIF-1α-deficient tumors also responded significantly to chemotherapy. These data introduce a previously undescribed and counterintuitive prohypoxia role for proangiogenic TEMs in breast cancer which is, in part, suppressed by HIF-2α.

The counterintuitive role of exercise in the prevention and cause of atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, characterized by irregular atrial activity. AF is related to increased risk of thromboembolic events, heart failure, and premature mortality. Recent advances in our understanding of its pathophysiology include a potentially central role for inflammation and presence of cardiovascular risk factors. The role of physical activity and exercise in the development and progression of AF, however, are not yet fully understood. Physical activity is protective for modifiable cardiovascular risk factors, including those associated with AF. Indeed, emerging research has demonstrated beneficial effects of exercise on AF-specific outcomes, including AF recurrence postablation. Counterintuitively, the prevalence of AF in veteran endurance athletes seems higher compared with the general population. In this review, we discuss the novel evidence and underlying mechanisms underpinning the role of exercise as medicine in the development and management of AF but also the counterintuitive detrimental role of excessive endurance exercise. Finally, we advocate regular (but not long-term high-intensity endurance) exercise training as a safe and effective strategy to reduce the risk of incident AF and to minimize the associated risk of secondary cardiovascular events.

Accelerated Reduction of 4-Nitrophenol: Bridging Interaction Outplays Reducing Power in the Model Nanoparticle-Catalyzed Reaction

General chemistry knowledge will intuitively predict that a stronger reducing agent will result in a faster reduction reaction. The present work, however, shows the counterintuitive role of reducin...