Relevant Structures Research Articles

Three-Dimensional Imaging of Bioinspired Lipidic Mesophases Using Multicolored Light-Emitting Carbon Nanodots.

Recent progress in the design of carbon nanostructures exhibiting strong multiphoton-excited emission opens new pathways to explore the self-organization of lipids found in living organisms. Phospholipid-based lyotropic myelin figures (MFs) are promising materials as simplified models of biomembranes due to their structural resemblance to a multilamellar sheath insulating the axon. This study demonstrates the possibility of selective labeling of MFs by strongly emitting multicolor phloroglucinol-derived carbon nanodots (PG CNDs). Such dopants are efficiently excited by visible and near-infrared light; therefore, one- and two-photon fluorescence microscopies are incorporated to gain 3D insights into the MFs. Combining nondestructive fluorescence microscopy and spectroscopy techniques along with polarized light microscopy gives details on the stability and morphology of lipidic mesophases. Our findings suggest that PG CNDs can be a viable and simple alternative to conventional fluorescent lipid stains to image biologically relevant phospholipid-based structures.

Transmittance‐based Extinction and Viewpoint Optimization

AbstractA long‐standing challenge in volume visualization is the effective communication of relevant spatial structures that might be hidden due to occlusions. Given a scalar field that indicates the importance of every point in the domain, previous work synthesized volume visualizations by weighted averaging of samples along view rays or by optimizing a spatially‐varying extinction field through an energy minimization. This energy minimization, however, did not directly measure the contribution of an individual sample to the final pixel color. In this paper, we measure the visibility of relevant structures directly by incorporating the transmittance into a non‐linear energy minimization. For the first time, we not only perform a transmittance‐based extinction optimization, we concurrently optimize the camera position to find ideal viewpoints. We derive the partial derivatives for the gradient‐based optimization symbolically, which makes the application of automatic differentiation methods unnecessary. The transmittance‐based formulation gives a direct visibility measure that is communicated to the user in order to make aware of potentially overlooked relevant structures. Our approach is compatible with any measure of importance and its versatility is demonstrated in multiple data sets.

Evaluating Performance of Different RNA Secondary Structure Prediction Programs Using Self-cleaving Ribozymes.

Accurate identification of the correct, biologically relevant RNA structures is critical to understanding various aspects of RNA biology since proper folding represents the key to the functionality of all types of RNA molecules and plays pivotal roles in many essential biological processes. Thus, a plethora of approaches have been developed to predict, identify, or solve RNA structures based on various computational, molecular, genetic, chemical, or physicochemical strategies. Purely computational approaches hold distinct advantages over all other strategies in terms of the ease of implementation, time, speed, cost, and throughput, but they strongly underperform in terms of accuracy that significantly limits their broader application. Nonetheless, the advantages of these methods led to a steady development of multiple in silico RNA secondary structure prediction approaches including recent deep learning-based programs. Here, we compared the accuracy of predictions of biologically relevant secondary structures of dozens of self-cleaving ribozyme sequences using seven in silico RNA folding prediction tools with tasks of varying complexity. We found that while many programs performed well in relatively simple tasks, their performance varied significantly in more complex RNA folding problems. However, in general, a modern deep learning method outperformed the other programs in the complex tasks in predicting the RNA secondary structures, at least based on the specific class of sequences tested, suggesting that it may represent the future of RNA structure prediction algorithms.

In a circuit necessary for cognition and emotional affect, Alzheimer's-like pathology associates with neuroinflammation, cognitive and motivational deficits in the young adult TgF344-AD rat

In addition to extracellular amyloid plaques, intracellular neurofibrillary tau tangles, and inflammation, cognitive and emotional affect perturbations are characteristic of Alzheimer's disease (AD). The cognitive and emotional domains impaired by AD include several forms of decision making (such as intertemporal choice), blunted motivation (increased apathy), and impaired executive function (such as working memory and cognitive flexibility). However, the interaction between these domains of the mind and their supporting neurobiological substrates at prodromal stages of AD, or whether these interactions can be predictive of AD severity (individual variability), remain unclear. In this study, we employed a battery of cognitive and emotional tests in the young adult (5–7 mo) transgenic Fisher-344 AD (TgF344-AD; TgAD) rat model of AD. We also assessed whether markers of inflammation or AD-like pathology in the prelimbic cortex (PrL) of the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), or nucleus accumbens (NAc), all structures that directly support the aforementioned behaviors, were predictive of behavioral deficits. We found TgAD rats displayed maladaptive decision making, greater apathy, and impaired working memory that was indeed predicted by AD-like pathology in the relevant brain structures, even at an early age. Moreover, we report that the BLA is an early epicenter of inflammation, and notably, AD-like pathology in the PrL, BLA, and NAc was predictive of BLA inflammation. These results suggest that operant-based battery testing may be sensitive enough to determine pathology trajectories, including neuroinflammation, from early stages of AD.

Joint inversion of induced polarization and hydraulic tomography data for hydraulic conductivity imaging

SUMMARY For accurate modelling of groundwater flow and transport processes within an aquifer, precise knowledge about hydraulic conductivity K and its small-scale heterogeneities is fundamental. Methods based on pumping tests, such as hydraulic tomography (HT), allow for retrieving reliable K-estimates, but are limited in their ability to image structural features with high resolution, since the data from time-consuming hydraulic tests are commonly sparse. In contrast, geophysical methods like induced polarization (IP) can potentially yield structural images of much higher resolution, but depend on empirical petrophysical laws that may introduce significant uncertainties to the K-estimation. Therefore, this paper presents a joint inversion procedure for both HT and IP data, which allows for combining the complementary abilities of both methods. Within this approach, a traveltime inversion is applied to the HT data, while the IP inversion is based on a full-decay time-domain forward response, as well as a reparametrization of the Cole–Cole model to invert for K directly. The joint inversion is tested on a synthetic model mimicking horizontally layered sediments, and the results are compared with the individual HT and IP inversions. It is shown that jointly inverting both data sets consistently improves the results by combining the complementary sensitivities of the two methods, and that the inversion is more robust against changes in the experimental setups. Furthermore, we illustrate how a joint inversion approach can correct biases within the petrophysical laws by including reliable K-information from hydraulic tests and still preserving the high-resolution structural information from IP. The different inversion results are compared based on the structural similarity index (SSIM), which underlines the robustness of the joint inversion compared to using the data individually. Hence, the combined application of HT and IP within field surveys and a subsequent joint inversion of both data sets may improve our understanding of hydraulically relevant subsurface structures, and thus the reliability of groundwater modelling results.

Digitalization attempts in higher education: the role of imprinting and the effect of business departments

ABSTRACT In recent decades, higher education institutions (HEIs) have increasingly been exposed to a market logic that has led them to adopt structures and practices that are common in for-profit firms. In our study, we analyze how HEIs react to the increasing demands of digitalization and which factors explain the adoption of relevant structures. Based on 379 HEIs in Germany, our findings show that imprinting is of great importance for the implementation of a position for digitalization – that is, HEIs founded in a more recent phase of higher education in Germany are more likely to create a leadership position for digitalization. At the same time, we find that imprinting has no effect on the creation of more operational positions for digitalization but that the existence of a business department in HEIs has a positive effect. We discuss these findings in the context of higher education research and questions about factors influencing the adoption of practices and structures in HEIs.

Unlocking the potential of protein-derived peptides to target G-quadruplex DNA: from recognition to anticancer activity.

Noncanonical nucleic acid structures, particularly G-quadruplexes, have garnered significant attention as potential therapeutic targets in cancer treatment. Here, the recognition of G-quadruplex DNA by peptides derived from the Rap1 protein is explored, with the aim of developing novel peptide-based G-quadruplex ligands with enhanced selectivity and anticancer activity. Biophysical techniques were employed to assess the interaction of a peptide derived from the G-quadruplex-binding domain of the protein with various biologically relevant G-quadruplex structures. Through alanine scanning mutagenesis, key amino acids crucial for G-quadruplex recognition were identified, leading to the discovery of two peptides with improved G-quadruplex-binding properties. However, despite their in vitro efficacy, these peptides showed limited cell penetration and anticancer activity. To overcome this challenge, cell-penetrating peptide (CPP)-conjugated derivatives were designed, some of which exhibited significant cytotoxic effects on cancer cells. Interestingly, selected CPP-conjugated peptides exerted potent anticancer activity across various tumour types via a G-quadruplex-dependent mechanism. These findings underscore the potential of peptide-based G-quadruplex ligands in cancer therapy and pave the way for the development of novel therapeutic strategies targeting these DNA structures.

Pro-cognitive effects of dual tacrine derivatives acting as cholinesterase inhibitors and NMDA receptor antagonists

Therapeutic options for Alzheimer’s disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine derivatives inhibiting acetylcholinesterase (AChE) and simultaneously N-methyl-D-aspartate (NMDA) receptors. Compounds with balanced inhibitory potencies for the target proteins (K1578 and K1599) or increased potency for AChE (K1592 and K1594) were studied to identify the most promising pro-cognitive compound. Their effects were studied in cholinergic (scopolamine-induced) and glutamatergic (MK-801-induced) rat models of cognitive deficits in the Morris water maze. Moreover, the impacts on locomotion in the open field and AChE activity in relevant brain structures were investigated. The effect of the most promising compound on NMDA receptors was explored by in vitro electrophysiology. The cholinergic antagonist scopolamine induced a deficit in memory acquisition, however, it was unaffected by the compounds, and a deficit in reversal learning that was alleviated by K1578 and K1599. K1578 and K1599 significantly inhibited AChE in the striatum, potentially explaining the behavioral observations. The glutamatergic antagonist dizocilpine (MK-801) induced a deficit in memory acquisition, which was alleviated by K1599. K1599 also mitigated the MK-801-induced hyperlocomotion in the open field. In vitro patch-clamp corroborated the K1599-associated NMDA receptor inhibitory effect. K1599 emerged as the most promising compound, demonstrating pro-cognitive efficacy in both models, consistent with intended dual effect. We conclude that tacrine has the potential for development of derivatives with dual in vivo effects. Our findings contributed to the elucidation of the structural and functional properties of tacrine derivatives associated with optimal in vivo pro-cognitive efficacy.

Masked pre-training of transformers for histology image analysis

In digital pathology, whole-slide images (WSIs) are widely used for applications such as cancer diagnosis and prognosis prediction. Vision transformer (ViT) models have recently emerged as a promising method for encoding large regions of WSIs while preserving spatial relationships among patches. However, due to the large number of model parameters and limited labeled data, applying transformer models to WSIs remains challenging. In this study, we propose a pretext task to train the transformer model in a self-supervised manner. Our model, MaskHIT, uses the transformer output to reconstruct masked patches, measured by contrastive loss. We pre-trained MaskHIT model using over 7000 WSIs from TCGA and extensively evaluated its performance in multiple experiments, covering survival prediction, cancer subtype classification, and grade prediction tasks. Our experiments demonstrate that the pre-training procedure enables context-aware understanding of WSIs, facilitates the learning of representative histological features based on patch positions and visual patterns, and is essential for the ViT model to achieve optimal results on WSI-level tasks. The pre-trained MaskHIT surpasses various multiple instance learning approaches by 3% and 2% on survival prediction and cancer subtype classification tasks, and also outperforms recent state-of-the-art transformer-based methods. Finally, a comparison between the attention maps generated by the MaskHIT model with pathologist's annotations indicates that the model can accurately identify clinically relevant histological structures on the whole slide for each task.

Endoscope-assisted microvascular decompression in hemifacial spasm with a teflon bridge

BackgroundMicrovascular conflicts in hemifacial spasm typically occur at the facial nerve’s root exit zone. While a pure microsurgical approach offers only limited orientation, added endoscopy enhances visibility of the relevant structures without the necessity of cerebellar retraction.MethodsAfter a retrosigmoid craniotomy, a microsurgical decompression of the facial nerve is performed with a Teflon bridge. Endoscopic inspection prior and after decompression facilitates optimal Teflon bridge positioning.ConclusionsEndoscope-assisted microsurgery allows a clear visualization and safe manipulation on the facial nerve at its root exit zone.

A thermo-mechanical constitutive model for triple-shape and two-way shape memory polymers

Semicrystalline polymers often have diverse molecular configurations in response to the variation of temperature, making it easier to realize multiple or two-way shape memory effects (SMEs). In order to provide guidance for the design of relevant smart structures, it is necessary to develop corresponding constitutive models to better characterize the thermal-mechanical behavior of such shape memory polymers (SMPs). For the first time, a thermo-mechanical finite deformation constitutive model is presented to reveal the deformation mechanism of the triple-shape two-way SME of semicrystalline SMPs in our work, based on the theory of thermodynamics with internal state variables. To verify the validity of the model, the model results are compared with the test data for a typical shape memory cycle. It is found that the model can be employed to describe the non-equilibrium response of semicrystalline SMPs with two types of crystallites in the vicinity of crystallization and melting. Since the model results fit well with the test data, the effectiveness of the model in predicting the triple two-way shape memory behavior is demonstrated.

Anatomia radiológica do tórax na graduação médica: o que o médico generalista precisa saber

Rationale: in medical education, the traditionally employed methodology in Human Anatomy classes is the dissection of cadavers, a method fraught with logistical, ethical, and financial limitations. In this context, the use of imaging exams not only contributes to the teaching of human anatomy, which is fundamental knowledge for professionals, but also facilitates an understanding of radiology, which is subsequently addressed in medical school. Furthermore, imaging exams represent one of the primary applications of anatomy in medical practice. Objectives: The present study aims to develop a proposal for an Essential Curriculum in Radiological Anatomy of the chest, outlining the fundamental structures to be identified in imaging exams by general practitioner and supporting the teaching of anatomy in medical education. Methods: A questionnaire was sent to medical professors and/or preceptors at the PUCPR medical school, where they were asked to assess the relevance of thoracic anatomical structures in the context of radiology on a 4-point Likert scale. The questionnaire was structured into four sections based on the most used imaging exams. The responses were entered into an Excel® spreadsheet and statistically analyzed for consensus using the Loe Index. Structures with high and moderate consensus among experts were included in the Core Curriculum. Results: The study included 26 medical professors and preceptors from PUCPR's medical school, representing 15 different medical specialties. The proposed Core Curriculum comprises 43 out of the initially listed 94 structures. Conclusion: In line with the stated objective, the result of this study is the development of a Core Curriculum in Radiological Anatomy of the Chest, consisting of 43 relevant structures to assist professionals in the evaluation of X-ray and computed tomography exams.

Secreted dengue virus NS1 from infection is predominantly dimeric and in complex with high-density lipoprotein

Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover the biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from dengue virus (DENV)-infected Vero cells through immunoaffinity purification instead of recombinant sNS1 (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as an approximately 250 kDa complex of NS1 and ApoA1 and further determined the cryoEM structures of isNS1 and its complex with a monoclonal antibody/Fab. Indeed, we found that the major species of isNS1 is a complex of the NS1 dimer partially embedded in a high-density lipoprotein (HDL) particle. Crosslinking mass spectrometry studies confirmed that the isNS1 interacts with the major HDL component ApoA1 through interactions that map to the NS1 wing and hydrophobic domains. Furthermore, our studies demonstrated that the sNS1 in sera from DENV-infected mice and a human patient form a similar complex as isNS1. Our results report the molecular architecture of a biological form of sNS1, which may have implications for the molecular pathogenesis of dengue.

Secreted dengue virus NS1 from infection is predominantly dimeric and in complex with high-density lipoprotein.

Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover the biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from dengue virus (DENV)-infected Vero cells through immunoaffinity purification instead of recombinant sNS1 (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as an approximately 250 kDa complex of NS1 and ApoA1 and further determined the cryoEM structures of isNS1 and its complex with a monoclonal antibody/Fab. Indeed, we found that the major species of isNS1 is a complex of the NS1 dimer partially embedded in a high-density lipoprotein (HDL) particle. Crosslinking mass spectrometry studies confirmed that the isNS1 interacts with the major HDL component ApoA1 through interactions that map to the NS1 wing and hydrophobic domains. Furthermore, our studies demonstrated that the sNS1 in sera from DENV-infected mice and a human patient form a similar complex as isNS1. Our results report the molecular architecture of a biological form of sNS1, which may have implications for the molecular pathogenesis of dengue.

Refugees in Trans-Border Conflict: The Case of Sierra Leone, 1991–2002

The victimization of refugees in the recipient communities has been broadly explored, especially in the context of West African civil wars, however the role refugees had in armed violence against local population and in the maintenance of the regional conflict economy requires further research. In this article, the author examines matters of refugee involvement in a civil war ravaging the recipient country based on the case of Sierra Leone conflict (1991–2002) and role that Liberian refugees played at the outset and different periods of war. The primary aim of this study is to determine the extent to which the role refugees played in the Sierra Leone conflict went beyond the traditional perception of refugee victimhood, the transformation of their involvement in war and the influence of the various regional and extra-regional forces. The existing academic literature on conflict in Sierra Leone is evaluated in accordance with the topic in focus and the extent to which this national experience can be applied to a broader set of regional wars. The role of refugees in trans-border economy is appraised in the theoretical framework of conflict support networks elaborated by William Reno and Jennifer Hazen using the functional analysis methodology treating civil wars as dynamic, with shifting intentions and roles of parties considered. Overall, the article provides additional angle in appraisal of the conflicts in West Africa and the cases of refugees’ involvement in these wars. The Liberian refugees had a changing active role in the conflict, gradually getting entangled in hostilities, illicit actions and violent entrepreneurship, turning from the victims of regional wars with their grievances into the destabilizing force for the recipient state of Sierra Leone and the entire region. The article is based on the materials of the Special Court for Sierra Leone, reports of international humanitarian organizations and documentation of the relevant state structures.

CountASAP: A Lightweight, Easy to Use Python Package for Processing ASAPseq Data.

Declining sequencing costs coupled with the increasing availability of easy-to-use kits for the isolation of DNA and RNA transcripts from single cells have driven a rapid proliferation of studies centered around genomic and transcriptomic data. Simultaneously, a wealth of new techniques have been developed that utilize single cell technologies to interrogate a broad range of cell-biological processes. One recently developed technique, transposase-accessible chromatin with sequencing (ATAC) with select antigen profiling by sequencing (ASAPseq), provides a combination of chromatin accessibility assessments with measurements of cell-surface marker expression levels. While software exists for the characterization of these datasets, there currently exists no tool explicitly designed to reformat ASAP surface marker FASTQ data into a count matrix which can then be used for these downstream analyses. To address this, we created CountASAP, an easy-to-use Python package purposefully designed to transform FASTQ files from ASAP experiments into count matrices compatible with commonly-used downstream bioinformatic analysis packages. CountASAP takes advantage of the independence of the relevant data structures to perform fully parallelized matches of each sequenced read to user-supplied input ASAP oligos and unique cell-identifier sequences.

PIWI-Interacting RNAs: A Pivotal Regulator in Neurological Development and Disease.

PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs (sncRNAs) with 24-32 nucleotides (nt), were initially identified in the reproductive system. Unlike microRNAs (miRNAs) or small interfering RNAs (siRNAs), piRNAs normally guide P-element-induced wimpy testis protein (PIWI) families to slice extensively complementary transposon transcripts without the seed pairing. Numerous studies have shown that piRNAs are abundantly expressed in the brain, and many of them are aberrantly regulated in central neural system (CNS) disorders. However, the role of piRNAs in the related developmental and pathological processes is unclear. The elucidation of piRNAs/PIWI would greatly improve the understanding of CNS development and ultimately lead to novel strategies to treat neural diseases. In this review, we summarized the relevant structure, properties, and databases of piRNAs and their functional roles in neural development and degenerative disorders. We hope that future studies of these piRNAs will facilitate the development of RNA-based therapeutics for CNS disorders.

The development and cross-cultural validation of a Student Online Learning Experience Scale

ABSTRACT A growing body of research has explored the effects of Covid-19-induced online learning on students’ experiences. However, there is a lack of validated tools that measure the perceived online learning experiences of domestic and international students in various national and cultural contexts. To address this gap, this article aims to develop the Student Online Learning Experience Scale (SOLE-S). We conceptualised four potential dimensions of students’ perceptions of their online learning experiences: online interactions with students, teachers, university, and technology (i.e. students’ capacity to participate in online learning). Confirmatory factor analysis determined three distinct factors: online interactions with students, the university (including teachers), and technology. Based on multiple validation studies reported in this article, the 10-item SOLE-S demonstrated sound internal consistency, discriminant validity, and convergent validity. Multigroup confirmatory factor analysis on data from domestic and international students transitioning from conventional classroom learning to online learning during the COVID-19 pandemic in Italy, France, Poland, and the UK showed a stable factor structure across different cultural contexts. Bivariate and point-biserial correlation analyses revealed that the SOLE-S is associated with students’ adjustment, performance, satisfaction, and loyalty to the university. This tool will assist higher education institutions in monitoring students’ online learning experiences and developing relevant support structures to enhance their academic experience and well-being during the pandemic and post-pandemic online learning.

Diagnostic yield of dental radiography and digital tomosynthesis for the identification of anatomic structures in cats.

Digital tomosynthesis (DT) has emerged as a potential imaging modality for evaluating anatomic structures in veterinary medicine. This study aims to validate the diagnostic yield of DT in identifying predefined anatomic structures in feline cadaver heads, comparing it with conventional intraoral dental radiography (DR). A total of 16 feline cadaver heads were utilized to evaluate 19 predefined clinically relevant anatomic structures using both DR and DT. A semi-quantitative scoring system was employed to characterize the ability of each imaging method to identify these structures. DT demonstrated a significantly higher diagnostic yield compared to DR for all evaluated anatomic structures. Orthogonal DT imaging identified 13 additional anatomic landmarks compared to a standard 10-view feline set obtained via DR. Moreover, DT achieved statistically significant higher scores for each of these landmarks, indicating improved visualization over DR. These findings validate the utility of DT technology in reliably identifying clinically relevant anatomic structures in the cat skull. This validation serves as a foundation for further exploration of DT imaging in detecting dentoalveolar and other maxillofacial bony lesions and pathologies in cats.

Experimental investigation on fluid-induced vibration of a semi-submerged flexible pipe in oncoming flows

Fluid-induced vibration (FIV) features of the semi-submerged flexible pipe in an oncoming flow are experimentally investigated in this paper. The flexible pipe is towed to simulate the equivalent uniform oncoming flow with a Froude number (Fr) ranging from 0.2 to 2.5. The overtopping states are determined and divided into three regions by the Fr numbers, including non-overtopping, intermitting overtopping, and continuous overtopping regions. Through the displacement reconstruction and wavelet transform methods, the displacement response, frequency, trajectory, and the chaotic characteristics of the semi-submerged pipe are studied. The results show that the FIV displacement responses are evidently affected by the intensity of the overtopping phenomenon. A significant mean displacement in the cross flow (CF) direction can be seen and a maximum value of 0.88D can be reached. The unexpectedly larger FIVs with standard deviation values of around 0.52D can be witnessed in the in-line (IL) direction than those for a fully submerged pipe. Moreover, the FIV frequency response in the IL direction is found to be consistent with that in the CF direction under intermitting overtopping and continuous overtopping state, and the corresponding Strouhal numbers are 0.24 and 0.28, respectively. The FIV response is found to be chaotic in non-overtopping states, while it behaves periodic and quasiperiodic features as overtopping occurs. The “O” shape of the motion trajectory is observed at such overtopping regions. The present work improves the basic understanding of the FIV features of the semi-submerged flexible pipe in the oncoming flow and can provide useful references for designing the relevant marine structures.