Search Results (137)

The increasing power density of 2.5D and 3D chiplets imposes severe thermal constraints that have a direct impact on the performance and long-term reliability of high-performance computing systems. Stacked and laterally integrated dies, which generate hundreds of watts per package, create localized hotspots and inconsistent temperature fields, major obstacles to scalable heterogeneous integration. Research efforts have addressed these challenges by finite element and compact heat modeling, thermal interface material optimization (TIM), and advanced cooling solutions such as micro-channel liquid cooling and cold racks. While these approaches provide valuable insights, most remain case-specific, focusing on isolated packages or single design variables, and lack a general methodology for assessing thermal feasibility at an early stage. This review consolidates and critically analyzes contributions to thermal modeling at the package level, interposer thermal spreading, thermal characterization of TIMs, and the development of cooling technologies. A comparative review of published studies indicates a consistent threshold: 2.5D stacks are viable under air cooling at approximately 300 W, whereas 3D stacks require liquid or hybrid cooling in conjunction with high-performance thermal interface materials at about 350 W. The investigations identify interposer conductivity, thermal interface material thickness, and hotspot power distribution as the primary sensitivity elements. This study explores Thermal Feasibility Maps (TFMs), defined as multidimensional charts parameterized by architecture, cooling regime, and material stack. TFMs provide a systematic framework for comparing design trade-offs and support architecture cooling co-design in advanced chiplet systems. Full article

Background: Rabies is among the oldest known zoonotic viral diseases and is caused by members of the Lyssavirus genus. The prototype species, Lyssavirus rabies, effectively evades the host immune response, allowing the infection to progress unnoticed until the onset of clinical signs. At this stage, the disease is irreversible and invariably fatal, with definitive diagnosis possible only post-mortem. Given the advances in modern proteomics, this study aimed to identify potential protein biomarkers for antemortem diagnosis of rabies in dogs, which are the principal reservoir hosts of the rabies virus. Methods: Two hundred and thirty-one samples (brain tissues (BT), cerebrospinal fluids (CSF), and serum (SR) samples) were collected from apparently healthy dogs brought for slaughter for human consumption in South-East and North-Central Nigeria. All the BT were subjected to a direct fluorescent antibody test to confirm the presence of lyssavirus antigen, and 8.7% (n = 20) were positive. Protein extraction, quantification, reduction, and alkylation were followed by on-bead (HILIC) cleanup and tryptic digestion. The resulting peptides from each sample were injected into the Evosep One LC system, coupled to the timsTOF HT MS, using the standard dia-PASEF short gradient data acquisition method. Data was processed using Spectronaut^TM (v19). An unpaired t-test was performed to compare identified protein groups (proteins and their isoforms) between the rabies-infected and uninfected BT, CSF, and SR samples. Results: The study yielded 54 significantly differentially abundant proteins for the BT group, 299 for the CSF group, and 280 for the SR group. Forty-five overlapping differentially abundant proteins were identified between CSF and SR, one between BT and CSF, and two between BT and SR; none were found that overlapped all three groups. Within the BT group, 33 proteins showed increased abundance, while 21 showed decreased abundance in the rabies-positive samples. In the CSF group, 159 proteins had increased abundance and 140 had decreased abundance in the rabies-positive samples. For the SR group, 215 proteins showed increased abundance, and 65 showed decreased abundance in the rabies-positive samples. Functional enrichment analysis revealed that pathways associated with CSF, spinocerebellar ataxia, and neurodegeneration were among the significant findings. Conclusion: This study identified canonical proteins in CSF and SR that serve as candidate biomarkers for rabies infection, offering insights into neuronal dysfunction and potential tools for early diagnosis. Full article

Since the late 1970s, satellite missions have monitored Total Solar Irradiance (TSI), providing a long-term record of solar variability. The Digital Absolute Radiometer (DARA), onboard the Chinese Fengyun-3E (FY3E) spacecraft since 4 July 2021, contributes to extending this record. In this study, we evaluate the DARA observations in both World Radiometric Reference (WRR) and International System of Units (SI) scales. We compare these records with those from other instruments on different spacecraft (i.e., VIRGO/PMO6, TSIS-1/TIM) and with the co-located Solar Irradiance Absolute Radiometer (SIAR) on FY3E. A key finding is the identification and correction of an instrumental artifact: an issue in the thermal aperture model, linked to annual satellite maneuvers, repetitively introduced an artificial step of 0.15 ± 0.05 Wm⁻² into the TSI measurements. A statistical analysis of the measurements in the SI scale shows that the mean value of the DARA TSI observations is approximately 1359.58 Wm⁻² (6-hourly rate), which is lower than the ones recorded by VIRGO/PMO6 (1.82 Wm⁻²), TSIS-1/TIM (2.90 Wm⁻²), and SIAR (2.54 Wm⁻²). We estimate a degradation of ∼49 ppm over 46 months due to the exposure of the instrument to the (Extreme) Ultraviolet (UV/EUV) radiations. Finally, the corrected DARA observations are incorporated into the long-term TSI composite time series. Comparison with the PMOD/WRC composite shows only marginal differences (less than 0.015 Wm⁻²), confirming the consistency and reliability of including the new TSI product (i.e., JTSIM-DARAv1). Full article

We present ID-TIMS U-Pb single zircon ages and major and trace element data for granitoid plutons from the Imorona–Itsindro and Kiangara suites in central Madagascar, in order to constrain the timing of igneous emplacement and investigate the petrogenesis and tectonic settings of these Neoproterozoic plutons. A U-Pb crystallization age of 779 ± 7 Ma was determined from an Imorona–Itsindro intrusion, while a Kiangara intrusion yields 777 ± 4 Ma, older than previously reported. The identical U-Pb ages suggest contemporaneous emplacement of some Kiangara and Imorona–Itsindro intrusions. Elemental data indicate that the two suites display trace element patterns similar to those of arc-type magmas. Some distinct geochemical features are apparent between these two suites. The Imorona–Itsindro sample displays I-type affinity with low REE abundances, whereas the Kiangara samples exhibit A-type signatures with higher REE contents. We suggest that the elemental differences between A-type and I-type reflect the contamination of mantle-derived magma by lower and upper crustal rocks, respectively. We suggest that the coeval A-type and I-type granitoids in central Madagascar were generated in a subduction system associated with slab rollback and back-arc extension like extension. The compositional diversity in these Neoproterozoic plutons reflects the evolution of the tectonic regime within a single geodynamic environment, similar to that proposed for plutons in other Precambrian and younger terranes. Full article

This article examines how metaphors operate in digital media not as descriptive analogies but as structuring forces that shape how technologies are designed, understood, and inhabited. Building on Marianne van den Boomen’s theory of digital material metaphors, it argues that metaphors such as the “desktop,” “cloud,” and “frontier” encode social and ideological assumptions into the infrastructures of computation. These metaphors render digital systems legible while concealing not just the procedural computation that van den Boomen terms depresentation, but the material, ecological, and labour conditions that sustain them. Using my practice-based work c(o)racle, 2025, as a case study, the internet is explored as a metaphorical and material terrain that connects networks of data, water, and craft, interrogating the dominant metaphor of cyberspace as immaterial and untethered, in dialogue with Tim Ingold, Lakoff and Johnson, Henri Lefebvre, and Yuk Hui. Drawing on S. J. Tambiah, Bruno Latour, and Elizabeth Wayland Barber, the essay situates metaphor within broader histories of making and mediation. By activating metaphor as both method and medium, the study proposes a critical reorientation toward digital space as an entangled, situated, and contested environment. Full article

Efficient thermal management is critical for the safety and performance of lithium-ion battery (LIB) systems, particularly under high C-rate charge–discharge cycling. Here, we investigate two classes of polymer composite thermal interface materials (TIMs): graphene-PLA (GPLA) fabricated via 3D printing and boron nitride nanoplatelets (BN)-loaded thermoplastic polyurethane (TPU) composites with 20 and 40 wt.% BN content. To understand cooling dynamics, we developed a simple analytical model based on Newtonian heat conduction, predicting an inverse relationship between the cooling rate and the TIM thermal diffusivity. We validated this model experimentally using a six-cell LIB module equipped with active liquid cooling, and complemented it with finite-element simulations in COMSOL Multiphysics incorporating experimentally derived parameters. Across all approaches, analytical, numerical, and experimental, we observed excellent agreement in predicting the temperature decay profiles and inter-cell temperature differentials ($\mathrm{\Delta }T$). Charge–discharge cycling studies at varying C-rates demonstrated that high-diffusivity TIMs enable faster cooling but require careful design to minimize lateral thermal gradients. Our results establish that an ideal TIM must simultaneously support rapid vertical heat sinking and effective lateral thermal diffusion to ensure thermal uniformity. Among the studied materials, the 40% BN–60% TPU composite achieved the best overall performance, highlighting the potential of BN filler-engineered polymer composites for scalable thermal management in next-generation battery systems. Full article

Objective: T cell exhaustion is a major mechanism of immune evasion in cancer, characterized by the sustained expression of multiple inhibitory receptors. This study aimed to evaluate the expression of immune checkpoints in peripheral and tumor-infiltrating CD8⁺ T cells from cervical cancer patients. Methods: We enrolled 104 participants: 37 treatment-naïve patients, 36 treated patients, and 31 age-matched healthy donors. Peripheral blood mononuclear cells (PBMCs) were isolated from all participants. Ten cervical biopsies were collected for tumor-infiltrating lymphocyte (TIL) isolation and paraffin fixation. Immune checkpoint expression was analyzed by multiparametric flow cytometry and immunohistochemistry. Results: In peripheral CD8⁺ T cells, we found a significant upregulation of exhaustion-associated markers PD-1, TIGIT, Tim-3, and LAG-3. In the tumor infiltrating lymphocytes, these same molecules, with the addition of NKG2A, were notably upregulated further. While BTLA and NKG2A showed no systemic changes, NKG2A increased in TILs and BTLA decreased in TILs. The co-expression of PD-1 with TIGIT, Tim-3, LAG-3, and NKG2A was notably enriched between 2- and 6-fold in TILs compared with patient PBMCs. The tumor microenvironment was highly immunosuppressive, characterized by enrichment with PD-1, PD-L1, and TIGIT; TIGIT was notably upregulated in locally advanced versus early-stage tumors. Conclusions: Our findings highlight the strongly immunosuppressive environment of cervical tumors in treatment-naïve patients and the presence of elevated inhibitory checkpoint expression in peripheral blood of both pre- and post-treatment patients. These results underscore the importance of investigating immune regulation within the tumor site itself and suggest that immune checkpoint co-expression may serve as a biomarker of T cell exhaustion and therapeutic resistance. Understanding how treatment alters these pathways could guide rational combination immunotherapies to restore CD8⁺ T cell function in cervical cancer. Full article

The research presents the thermal performance comparison of silicone and non-silicone thermal pads using a steady-state thermal interface material (TIM) testing apparatus. The TIM tester follows standard guidelines for testing thermal properties. TIMs are applied between two solid surfaces to improve heat transfer by eliminating air gaps that naturally occur due to surface roughness and non-flatness. Since TIMs possess significantly higher thermal conductivity than air, they effectively reduce contact resistance at the interface, thereby minimizing the risk of overheating in electronic systems. In this work, the thermal resistances of silicone and non-silicone thermal pads were compared over a pressure range of 10–50 psi. Results indicate that non-silicone pads consistently exhibit lower thermal resistance than their silicone counterparts under identical testing conditions. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4⁺ and CD8⁺ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment. Full article

The growing demand for efficient thermal management in power electronics and high-density optoelectronic systems necessitates thermal interface materials (TIMs) with high through-plane thermal conductivity and minimal anisotropy. However, conventional polymer composites filled with platelet-type fillers such as hexagonal boron nitride (h-BN) suffer from strong directional thermal transport and interfacial resistance, limiting their practical effectiveness. To address this limitation, we present a hybrid filler strategy wherein h-BN and silicon carbide (SiC) nanoparticles interact via hydroxylated surfaces, forming a three-dimensional thermally conductive network. The resulting BN–SiC composite exhibits enhanced through-plane thermal conductivity (1.61 W/mK at 70 vol%) and lower anisotropy ratios (<2.0 at 30 vol%), all while maintaining mechanical integrity and processability. These results demonstrate that chemical bonding at the filler interface can reduce interfacial thermal resistance and extend thermal conduction paths three-dimensionally, providing insights into interface-based heat transfer mechanisms. This strategy presents a scalable and practical approach for next-generation thermal management solutions in electronic packaging and high-power device platforms. Full article

This work reviews the complex role of the enzyme triosephosphate isomerase (TIM) (EC 5.3.1.1) within the context of diabetes, a prevalent metabolic disorder. It summarizes the main biochemical pathways, cellular mechanisms, and molecular interactions that highlight both the function of TIM and its implications in diabetes pathophysiology, particularly focusing on its regulatory role in glucose metabolism and insulin secretion. TIM’s involvement is detailed from its enzymatic action in glycolysis, influencing the equilibrium between dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, to its broader implications in cellular metabolic processes. The article highlights how mutations in TIM can lead to metabolic inefficiencies that exacerbate diabetic conditions. It discusses the interaction of TIM with various cellular pathways, including its role in the ATP-sensitive potassium channels in pancreatic beta cells, which are crucial for insulin release. Moreover, we indicate the impact of oxidative stress in diabetes, noting how TIM is affected by reactive oxygen species, which can disrupt normal cellular functions and insulin signaling. The enzyme’s function is also tied to broader cellular and systemic processes, such as membrane fluidity and cellular signaling pathways, including the mammalian target of rapamycin, which are critical in the pathogenesis of diabetes and its complications. This review emphasizes the dual role of TIM in normal physiological and pathological states, suggesting that targeting TIM-related pathways could offer novel therapeutic strategies for managing diabetes. It encourages an integrated approach to understanding and treating diabetes, considering the multifaceted roles of biochemical players such as TIM that bridge metabolic, oxidative, and regulatory functions within the body. Full article

This study investigated the role of molecular mimicry in the context of autoimmunity associated with viral infection, using SARS-CoV-2 as a model system. A bioinformatic analysis was performed to identify sequence homologies between the SARS-CoV-2 Spike (S) protein and the human proteome, with a specific focus on immunogenic regions to assess potential cross-reactivity. The analysis revealed homologous regions between the viral S protein and several human proteins, including DAAM2, CHL1, HAVR2/TIM3, FSTL1, FHOD3, MYO18A, EMILIN3, LAMP1, and αENaC, which are predicted to be recognizable by B-cell receptors. Such recognition could potentially lead to the production of autoreactive antibodies, which can contribute to the development of autoimmune diseases. Furthermore, the study examined potential autoreactive CD4+ T-cell responses to human protein autoepitopes that could be presented by HLA class II molecules. Several HLA class II genetic variants were computationally associated with a higher likelihood of cross-reactive immune reactions following COVID-19, including HLA-DPA1*01:03/DPB1*02:01, HLA-DPA1*02:01/DPB1*01:01, HLA-DPA1*02:01/DPB1*05:01, HLA-DPA1*02:01/DPB1*14:01, HLA-DQA1*01:02/DQB1*06:02, HLA-DRB1*04:01, HLA-DRB1*04:05, HLA-DRB1*07:01, and HLA-DRB1*15:01. Additionally, seven T helper cell autoepitopes (YSEILDKYFKNFDNG, ERTRFQTLLNELDRS, AERTRFQTLLNELDR, RERKVEAEVQAIQEQ, NAINIGLTVLPPPRT, PQSAVYSTGSNGILL, TIRIGIYIGAGICAG) were identified that could be implicated in autoimmune T-cell responses through presentation by class II HLA molecules. These findings highlight the utility of viral B- and T-cell epitope prediction for investigating molecular mimicry as a possible mechanism in virus-associated autoimmunity. Full article

This paper introduces a compact analog configuration that concurrently realizes a mixed-mode biquadratic filter and a dual-mode quadrature oscillator (QO) by employing a single differential differencing gain amplifier (DDGA) and all-grounded passive components. The proposed design supports four fundamental operation modes—voltage-mode (VM), current-mode (CM), trans-impedance-mode (TIM), and trans-admittance-mode (TAM)—utilizing the same circuit topology without structural modifications. In filter operation, it offers low-pass, high-pass, band-pass, band-stop, and all-pass responses with orthogonal and electronic pole frequency and quality factor. In oscillator operation, it delivers simultaneous voltage and current quadrature outputs with independent tuning of oscillator frequency and condition. The grounded-component configuration simplifies layout and enhances its suitability for monolithic integration. Numerical simulations in a 0.18-μm CMOS process with ±0.9 V supply confirm theoretical predictions, demonstrating precise gain-phase characteristics, low total harmonic distortion (<7%), modest sensitivity to 5% component variations, and stable operation from −40 °C to 120 °C. These results, combined with the circuit’s low component count and integration suitability, suggest strong potential for future development in low-power IoT devices, adaptive communication front-ends, and integrated biomedical systems. Full article

Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization—spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways—including PI3K–AKT–mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades—undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome–lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3–CR3 axis), and excitatory–inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network “meaning-making”—a collapse of coordinated signal interpretation, triage prioritization, and adaptive response—the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning—a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration. Full article

Despite remarkable progress in cancer immunotherapy, many agents that show efficacy in murine or in vitro models fail to translate clinically. Zebrafish (Danio rerio) have emerged as a powerful complementary model that addresses several limitations of traditional systems. Their optical transparency, genetic tractability, and conserved immune and oncogenic signaling pathways enable high-resolution, real-time imaging of tumor–immune interactions in vivo. Importantly, zebrafish offer a unique opportunity to study the core mechanisms of health and sickness, complementing other models and expanding our understanding of fundamental processes in vivo. This review provides an overview of zebrafish immune system development, highlighting tools for tracking innate and adaptive responses. We discuss their application in modeling immune evasion, checkpoint molecule expression, and tumor microenvironment dynamics using transgenic and xenograft approaches. Platforms for high-throughput drug screening and personalized therapy assessment using patient-derived xenografts (“zAvatars”) are evaluated, alongside limitations, such as temperature sensitivity, immature adaptive immunity in larvae, and interspecies differences in immune responses, tumor complexity, and pharmacokinetics. Emerging frontiers include humanized zebrafish, testing of next-generation immunotherapies, such as CAR T/CAR NK and novel checkpoint inhibitors (LAG-3, TIM-3, and TIGIT). We conclude by outlining the key challenges and future opportunities for integrating zebrafish into the immuno-oncology pipeline to accelerate clinical translation. Full article