Search Results (170)

Here, we introduce a novel method for the real-time spatial monitoring of I/O interconnection nets in flip-flop packages. Resistance changes in 39 I/O nets are observed simultaneously to produce a spatial profile of the relative degradations of the solder ball joints, interconnection lines, and transistor gates. Location-specific TTF profiles are generated from the degradation data to show the impact of the I/O nets in the context of their placement on the chip. The system succeeds in formulating a clear trend of resistance increase even in relatively mild constant temperature stress conditions. Test results of four temperatures from 80 °C to 120 °C show a dominant degradation pattern strongly influenced by BTI aging demonstrating an acute vulnerability in the pass gates to voltage and temperature stress. The proposed compact spatial monitor solution can be integrated into virtually all chip orientations. The outcome of this study can assist in foreseeing system vulnerabilities in a large spectrum of packaging and advanced packaging orientations in field applications. Full article

Liposomes are nanoscale, spherical vesicles composed of phospholipid bilayers, typically ranging from 50 to 200 nm in diameter. Their unique ability to encapsulate both hydrophilic and hydrophobic molecules makes them powerful nanocarriers for drug delivery, diagnostics, and vaccine formulations. Several FDA-approved formulations such as Doxil^® (Baxter Healthcare Corporation, Deerfield, IL, USA), AmBisome^® (Gilead Sciences, Inc., Foster City, CA, USA), and Onivyde^® (Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ, USA) highlight their clinical significance. This review provides a comprehensive synthesis of how molecular dynamics (MD) simulations, particularly coarse-grained (CG) and atomistic approaches, advance our understanding of liposomal membranes. We explore key membrane biophysical properties, including area per lipid (APL), bilayer thickness, segmental order parameter ($S_{CD}$), radial distribution functions (RDFs), bending modulus, and flip-flop dynamics, and examine how these are modulated by cholesterol concentration, PEGylation, and curvature. Special attention is given to curvature-induced effects in spherical vesicles, such as lipid asymmetry, interleaflet coupling, and stress gradients across the leaflets. We discuss recent developments in vesicle modeling using tools such as TS2CG, CHARMM-GUI Martini Maker, and Packmol, which have enabled the simulation of large-scale, compositionally heterogeneous systems. The review also highlights simulation-guided strategies for designing stealth liposomes, tuning membrane permeability, and enhancing structural stability under physiological conditions. A range of CG force fields, MARTINI, SPICA, SIRAH, ELBA, SDK, as well as emerging machine learning (ML)-based models, are critically assessed for their strengths and limitations. Despite the efficiency of CG models, challenges remain in capturing long-timescale events and atomistic-level interactions, driving the development of hybrid multiscale frameworks and AI-integrated techniques. By bridging experimental findings with in silico insights, MD simulations continue to play a pivotal role in the rational design of next-generation liposomal therapeutics. Full article

Functional glycomimetics is suited to study the parameters of carbohydrate recognition that forms the basis of glycobiology. It is particularly attractive when a glycoligand allows for the investigation of two different states, such as varying distance between multiple glycoligands. Here, a xylopyranoside was employed as a scaffold for the presentation of two mannoside units which are ligands of the bacterial lectin FimH. The chair conformation of the central xyloside can be switched between a ⁴C₁ and a ¹C₄ conformation whereby the two conjugated mannoside ligands are flipped from a di-equatorial into a di-axial position. Concomitantly, the distance between the two glycoligands changes and, as a consequence, so does the biological activity of the respective bivalent glycocluster, as shown in adhesion–inhibition assays with live bacteria. Molecular modeling was employed to correlate the inter-ligand distance with the structure of the formed glycocluster–FimH complex. Our study suggests that conformational switches can be employed and further advanced as smart molecular tools to study structural boundary conditions of carbohydrate recognition in a bottom-up approach. Full article

In this paper, physics students’ experiences of a flipped, active learning physics class are explored through the lens of transactional distance theory (TDT). Transactional distance (TD) is the psychological and communicative distance that may arise between students and their teacher in learning environments such as large classes. TD has been shown to have a negative impact on students’ satisfaction, engagement, and learning outcomes, yet there is lack of research on how pedagogical approaches, such as the flipped classroom and active learning, may ameliorate the impacts of TD. In this paper, I use a qualitative methodology to gain an in-depth understanding of the ways in which a flipped class can impact the experience of transactional distance for first year physics students. Eleven students took part in semi-structured interviews about their experience of the class, from which three themes were developed: (a) creating connections; (b) stimulating engagement; and (c) supporting responsiveness. These themes are interpreted through the lens of TDT to understand the ways in which the flipped class and active learning pedagogics reduced students’ experience of TD. This gives new insights into students’ experiences of small group discussions, pre-class quizzes, and in-class ‘clicker’ questions. The implications for the pedagogical design of flipped classes will be discussed. Full article

Rafoxanide, originally developed as a veterinary anthelmintic for the treatment of parasitic infections in livestock, has recently emerged as a promising therapeutic prospect in oncology. This compound has demonstrated notable antineoplastic effects against a variety of cancers, including skin, gastric, colorectal, and lung cancers, as well as hematological malignancies such as multiple myeloma. Rafoxanide exerts its anticancer activity through multiple complementary mechanisms, including the induction of endoplasmic reticulum stress, cell cycle arrest, apoptosis, and immunogenic cell death. Furthermore, the drug has been reported to inhibit key oncogenic signaling pathways (e.g., STAT3, NF-κB, c-FLIP, survivin) that contribute to tumor growth and metastasis. Preclinical studies in murine models have demonstrated significant reductions in tumor volume of up to 50% and a tumor-free rate exceeding 80%, with effective doses ranging from 7.5 to 40 mg/kg. This multitargeted mode of action distinguishes rafoxanide from conventional therapies and may help overcome resistance mechanisms that often limit the efficacy of cancer treatments. In this review, we summarize and discuss the growing body of evidence supporting rafoxanide’s therapeutic potential in oncology, as well as its possible applications in cancer treatment. Full article

Norovirus, a major cause of acute gastroenteritis, possesses a single-stranded positive-sense RNA genome. The viral 3C-like cysteine protease (3CL^pro) plays a critical role in processing the viral polyprotein into mature non-structural proteins, a step essential for viral replication. Targeting 3CL^pro has emerged as a promising strategy for developing small-molecule inhibitors against Norovirus. In this study, we employed a combination of virtual screening and the FlipGFP assay to identify potential inhibitors targeting the 3CL^pro of Norovirus genotype GII.4. A library of approximately 58,800 compounds was screened using AutoDock Vina tool, yielding 20 candidate compounds based on their Max Affinity scores. These compounds were subsequently evaluated using a cell-based FlipGFP assay. Among them, eight compounds demonstrated significant inhibitory activity against 3CL^pro, with Gedatolisib showing the most potent effect (IC₅₀ = 0.06 ± 0.01 μM). Molecular docking and molecular dynamics simulations were conducted to explore the binding mechanisms and structural stability of the inhibitor–3CL^pro complexes. Our findings provide valuable insights into the development of antiviral drugs targeting Norovirus 3CL^pro, offering potential therapeutic strategies to combat Norovirus infections. Full article

Classroom engagement, a critical factor in enhancing learning outcomes and personal development, serves as a direct manifestation of students’ agency in learning. Understanding its developmental trajectory facilitates the efficient implementation of pedagogical activities. It also promotes students’ holistic development. This study aims to delineate the dynamic evolution of classroom engagement by constructing a network-based knowledge map, thereby revealing overarching research trends and shifts in this field. Systematically reviewing literature on classroom engagement since 1975, this research employs CiteSpace to visualize 919 articles sourced from the Web of Science Core Collection, offering valuable insights for theoretical exploration and practical applications in this domain. Key findings indicate: (1) a consistent increase in classroom engagement research over the past five decades; (2) the United States as the leading contributor; (3) Arizona State University, Texas A&M University College Station, and the University of California System as the most prolific institutions; (4) Fitzpatrick C as the most representative high-output author, with Fredricks JA being the most frequently cited scholar; (5) core journals including Journal of Educational Psychology, Review of Educational Research, and Child Development; and (6) emerging research hotspots such as flipped classroom, language, online education, and three focal themes: students with disabilities, interpersonal relationships, and student engagement. Full article

Artificial retinal devices require a high-density electrode array and mechanical flexibility to effectively stimulate retinal cells. However, designing such devices presents significant challenges, including the need to conform to the curvature of the eyeball and cover a large area using a single platform. To address these issues, we developed a parylene-based multi-module retinal device (MMRD) integrating a complementary metal-oxide semiconductor (CMOS) system. The proposed device is designed for suprachoroidal transretinal stimulation, with each module comprising a parylene-C thin-film substrate, a CMOS chip, and a ceramic substrate housing seven platinum electrodes. The smart CMOS system significantly reduces wiring complexity, enhancing the device’s practicality. To improve fabrication reliability, we optimized the encapsulation process, introduced multiple silane coupling modifications, and utilized polyvinyl alcohol (PVA) for easier detachment in flip-chip bonding. This study demonstrates the fabrication and evaluation of the MMRD through in vitro and in vivo experiments. The device successfully generated the expected current stimulation waveforms in both settings, highlighting its potential as a promising candidate for future artificial vision applications. Full article

Background: Leptomeningeal disease (LMD) is challenging to diagnose and monitor given the poor sensitivity of current gold-standard diagnostics. Cerebrospinal fluid tumor cells (CSF-TCs) have been studied as a biomarker for disease management because oncogene amplification of the primary, metastatic, and CNS metastatic tumors can be heterogeneous. The CNSide platform enumerates CSF-TCs and analyzes oncogene expression via immunocytochemistry (ICC), fluorescent in situ hybridization (FISH), and next-generation sequencing (NGS). We report the utility of this combined enumerative and mutational testing for LMD diagnosis and disease monitoring. Methods: A multicenter, retrospective analysis of commercially ordered assays from two health systems between January 2020 and July 2023 included 613 tests on 218 individual patients with suspected or confirmed LMD. To date, this is the largest cohort of patients in LMD literature evaluated using CSF-TCs. Results: CSF-TCs were detected in 67% (412/613) of samples. The most analyzed cancer types were breast (n = 105) and lung (n = 65). In lung cancer, anaplastic lymphoma kinase (ALK) was detected in 14% (17/118), and c-MET was detected in 61% (78/128). In breast cancer, HER2 was detected in 39% (65/168), and estrogen receptor (ER) was detected in 26% (44/168). Sixty-six patients underwent 2+ longitudinal CSF draws; among these, there were 58 flips in oncogene detection over time, and 30% (20/66) of patients had at least one biomarker change in the CSF. Conclusions: Longitudinal combined ICC/FISH/NGS CSF testing demonstrates a wide range in CSF-TC enumeration, which may be correlated with clinical course, and furthermore identifies actionable tumor markers that frequently fluctuate over time. Utilization of this platform would enable timely, personalized LMD-specific chemotherapy. Full article

This study aims to investigate the structural, spectroscopic, and electronic properties of the synthetic missile fuel exo- and endo-tetrahydrodicyclopentadiene (THDCPD, JP-10) using density functional theory (DFT). It is to understand the dominance of the liquid exo-isomer (96%) of the jet fuel from the subtle differences between the isomers. The present DFT calculations reveal that the exo-isomer is 15.51 kJ/mol more stable than the endo-isomer, attributed to the flipping of the triangular ΔC8-C10-C9 ring in its norbornane skeleton. Calculated nuclear magnetic resonance (¹³C-NMR) and infrared (IR) spectra, validated by experimental data, reveal larger chemical shifts for junction carbons (C1/C2 and C3/C4) due to reduced electron shielding and show distinct vibrational patterns. Charge analysis indicates that all carbon atoms are negatively charged except for the C1/C2 carbons which are positively charged in both isomers. While overall IR spectra of the isomers appear similar, bands near 3000 cm⁻¹ correspond to distinctly different vibrational modes. The exo-isomer’s electronic structure features a more delocalized HOMO and a larger HOMO-LUMO gap (7.63 eV) than the endo-isomer (7.37 eV). All such differences contribute to the properties of exo-THDCPD and, therefore, why the exo-isomer dominates JP-10 fuel. Full article

The purpose of this study was to evaluate the potential of using fuzzy C-means clustering, AMMI and GGE biplot analysis methods to predict the yield of chickpea (Cicer arietinum L.) genotypes grown in various environments. The trials were conducted in the Central, Silvan and Hazro districts of Diyarbakir province and Kiziltepe district of Mardin province in the Southeastern Anatolia Region of Türkiye. During the 2016 growing season, 19 chickpea genotypes were tested across four distinct environments. Multiple location experiments were used to assess the genotypes’ performance and stability. The study employed a two-factor experimental design in randomized blocks with four replications in each environment. As a result, the genotype FLIP98-206C showed the highest performance for yield (1727.3 kg ha⁻¹) at the Diyarbakır location among all locations. On the other hand, the Diyar-95 variety showed the lowest yield (723.5 kg ha⁻¹) at the Hazro location among all locations. The Diyarbakir location was determined as an ideal test environment for genotype selection in fuzzy C-means clustering, AMMI and GGE biplot analysis. The Silvan region was determined as the weakest environment for this purpose. It is considered that the determination of genotypes with high yield and stability in this research, in which different analysis methods were used in combination, will contribute to agricultural production. Full article

Tiny machine learning (TinyML) demands the development of edge solutions that are both low-latency and power-efficient. To achieve these on System-on-Chip (SoC) FPGAs, co-design methodologies, such as hls4ml, have emerged aiming to speed up the design process. In this context, fast estimation of FPGA’s utilized resources is needed to rapidly assess the feasibility of a design. In this paper, we propose a resource estimator for fully customized (bespoke) multilayer perceptrons (MLPs) designed through the hls4ml workflow. Through the analysis of bespoke MLPs synthesized using Xilinx High-Level Synthesis (HLS) tools, we developed resource estimation models for the dense layers’ arithmetic modules and registers. These models consider the unique characteristics inherent to the bespoke nature of the MLPs. Our estimator was evaluated on six different architectures for synthetic and real benchmarks, which were designed using Xilinx Vitis HLS 2022.1 targeting the ZYNQ-7000 FPGAs. Our experimental analysis demonstrates that our estimator can accurately predict the required resources in terms of the utilized Look-Up Tables (LUTs), Flip-Flops (FFs), and Digital Signal Processing (DSP) units in less than 147 ms of single-threaded execution. Full article

This paper presents a low power wideband dB-linear analog baseband (ABB) circuit for a millimeter-wave (mmW) wireless receiver in 40 nm CMOS technology. The proposed ABB system consists of a multi-stage variable gain amplifier (VGA) and a low-pass filter (LPF). The 5-stage VGA is composed of two variable gain units followed by three fixed gain units with DC offset cancellation (DCOC). The first variable gain unit with a self-compensated transistor pair and compact active inductor load is designed for dB-linear functionality and bandwidth extension, respectively. Moreover, a proposed error compensation method is applied to the second cascaded variable gain unit for further dB-linear gain error correction. A 4th-order Butterworth transconductance-capacitance (Gm-C) LPF with flipped source follower (FSF) as an input transconductance stage for linearity enhancement is designed after the VGA stage. The prototype chip is implemented, and measurement results show a dB-linear gain range from −18 to 26 dB with less than 0.5 dB-linear gain error with a bandwidth of 4 GHz. The VGA and LPF consume 8.3 mW and 3 mW, respectively, under a 1 V power supply, while the entire ABB occupies an area of 0.94 mm² with an active core area of only 0.045 mm². Full article

The FADD-like interleukin-1β converting enzyme (FLICE)-inhibitory protein (c-FLIP) plays a crucial role in various biological processes, including apoptosis and inflammation. However, the complete transcriptional profile altered by the c-FLIP is not fully understood. Furthermore, the impact of the c-FLIP deficiency on the transcriptome during a Zika virus (ZIKV) infection, which induces apoptosis and inflammation in the central nervous system (CNS), has not yet been elucidated. In this study, we compared transcriptome profiles between wild-type (WT) and the c-Flip heterozygous knockout mice (c-Flip^+/−) fetal heads at embryonic day 13.5 from control and PBS-infected WT dams mated with c-Flip^+/− sires. In the non-infected group, we observed differentially expressed genes (DEGs) mainly involved in embryonic development and neuron development. However, the ZIKV infection significantly altered the transcriptional profile between WT and the c-Flip^+/− fetal heads. DEGs in pattern recognition receptor (PRR)-related signaling pathways, such as the RIG-I-like receptor signaling pathway and Toll-like receptor signaling pathway, were enriched. Moreover, the DEGs were also enriched in T cells, indicating that the c-FLIP participates in both innate and adaptive immune responses upon viral infection. Furthermore, our observations indicate that DEGs are associated with sensory organ development and eye development, suggesting a potential role for the c-FLIP in ZIKV-induced organ development defects. Overall, we have provided a comprehensive transcriptional profile for the c-FLIP and its modulation during a ZIKV infection. Full article