Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipidoid nanoparticles increase ATP uptake into hypoxic brain endothelial cells

Lipidoid nanoparticles (LNPs) are clinically successful carriers for nucleic acid delivery to liver and muscle targets. Their ability to load and deliver small molecule drugs has not been reported yet. We propose that the delivery of adenosine triphosphate (ATP) to brain endothelial cells (BECs) lining the blood-brain barrier may increase cellular energetics of the injured BECs. We formulated and studied the physicochemical characteristics of ATP-loaded LNPs using the C12-200 ionizable cationic lipid and other helper lipids. Polyethylene glycol-dimyristoyl glycerol (PEG-DMG), one of the helper lipids, played a crucial role in maintaining colloidal stability of LNPs over time whereas the inclusion of both ATP and PEG-DMG maintained the colloidal stability of LNPs in the presence of serum proteins. ATP-LNPs formulated with PEG-DMG resulted in a 7.7- and 6.6-fold increased uptake of ATP into normoxic and hypoxic BECs, respectively. Altogether, our results demonstrate the potential of LNPs as a novel carrier for the delivery of small molecular mass actives to BECs—a CNS target. Highlights LNPs were formulated with ATP, a small molecule drug PEG-DMG plays a critical role in maintaining particle stability over tim ATP and PEG-DMG play a critical role in maintaining particle stability in 10% serum ATP-LNPs were internalized by normoxic and hypoxic brain endothelial cells (BECs) LNP delivery to BECs broadens its applicability to CNS targets Graphical Abstract
Hazel dormouse in managed woodland select for young, dense, and species-rich tree stands

In fragmented forest landscapes, population persistence of arboreal species with limited dispersal ability may strongly depend on the quality of the remaining forest habitat. Using the hazel dormouse (Muscardinus avellanarius) as a model species, we studied habitat selection at two spatial scales (home range and within home range) in intensely managed woodlands at its northern distributional range in Denmark. We modelled selection at home range level as the conditional probability of occupancy of 588 nest boxes and nest tubes in 15 managed forests relative to habitat variables measured within 25 m radius. Habitat selection within home ranges was modelled by comparing habitat variables within 3 m radius of triangulated locations by 19 radio-tracked individuals (12 M, 7 F) when active at night with regularly distributed available locations within their home ranges. At both spatial scales, hazel dormice strongly selected sites with high abundance-weighted species richness and high vegetation density of woody plants. On home range level, they furthermore selected for young tree vegetation, while they within home ranges selected for intermediate aged tree stands (maximum trunk circumference: 1.50 m). The predicted probability of presence in nest boxes or nest tubes varied from less than 1% to more than 99% as a combined function of three habitat variables. From May to October, selection for abundance-weighted species richness of woody plants of radio-tagged individuals decreased with date and body weight, suggesting that a diverse food base is particularly important early in their season of activity and for lean and small (growing) individuals. Selection for dense vegetation increased with body mass and mean available vegetation density within home ranges, indicating behavioural variability related to changes in energy expenditure and need for safety among individuals. The study demonstrates that the hazel dormouse has specific habitat requirements related to food and safety that can be accommodated with relatively simple means in managed forests. Graphical abstract
Oncogenic metabolic rewiring independent of proliferative control in human mammary epithelial cells

The use of isotopic tracers and metabolic flux analysis (MFA) has unveiled a number of metabolic pathways differentially activated in cancer cells. To support efforts to design effective metabolic therapies for cancer, we sought to distinguish metabolic behavior in cancer versus normal cells growing at the same rate. To this end, we performed 13C-isotope tracing and MFA in human mammary epithelial cells (HMECs) harboring different combinations of oncogenes. By introducing a new quantity termed metabolic flux intensity, defined as pathway flux divided by specific growth rate, we showed that metabolism is dually controlled by proliferation and oncogenotypes. 13C-MFA further revealed that oxidative pentose phosphate pathway (oxPPP), malate dehydrogenase (MDH) and isocitrate dehydrogenase (IDH) were most enhanced in cancerous HMECs. Drug targeting of these pathways selectively reduced growth in the tumorigenic HMEC line. Our study provides direct evidence that metabolism of cancer cells is different than that of normal proliferating cells.
Amoeboid Cell Migration through Regular Arrays of Micropillars under Confinement

Migrating cells often encounter a wide variety of topographic features—including the presence of obstacles—when navigating through crowded biological environments. Unravelling the impact of topography and crowding on the dynamics of cells is key to better understand many essential physiological processes such as the immune response. We study how migration and search efficiency of HL-60 cells differentiated into neutrophils in quasi two-dimensional environments are influenced by the lateral and vertical confinement and spatial arrangement of obstacles. A microfluidic device is designed to track the cells in confining geometries between two parallel plates with distance h, in which identical micropillars are arranged in regular pillar forests. We find that at each cell-pillar contact event, the cell spends a finite time near the pillar surface, which is independent of the height h and the interpillar spacing e. At low pillar density regime, the directional persistence of cells reduces with decreasing h or e, influencing their diffusivity and first-passage properties. The dynamics is strikingly different at high pillar density regime, where the cells are in simultaneous contact with more than one pillar; the cell velocity and persistence are distinctly higher compared to dilute pillar configurations with the same h. Our simulations reveal that the interplay between cell persistence and cell-pillar interactions can dramatically affect cell diffusivity and, thus, its first-passage properties.
High segregation and diminished global integration in large-scale brain functional networks enhances the perceptual binding of cross-modal stimuli

Speech perception requires the binding of spatiotemporally disjoint auditory–visual cues. The corresponding brain network-level information processing can be characterized by two complementary mechanisms: functional segregation which refers to the localization of processing in either isolated or distributed modules across the brain, and integration which pertains to cooperation among relevant functional modules. Here, we demonstrate using fMRI recordings that subjective perceptual experience of multisensory speech stimuli, real and illusory, are represented in differential states of segregation–integration. We controlled the inter-subject variability of illusory/cross-modal perception parametrically, by introducing temporal lags in the incongruent auditory–visual articulations of speech sounds within the McGurk paradigm. The states of segregation–integration balance were captured using two alternative computational approaches. First, the module responsible for cross-modal binding of sensory signals defined as the perceptual binding network (PBN) was identified using standardized parametric statistical approaches and their temporal correlations with all other brain areas were computed. With increasing illusory perception, the majority of the nodes of PBN showed decreased cooperation with the rest of the brain, reflecting states of high segregation but reduced global integration. Second, using graph theoretic measures, the altered patterns of segregation–integration were cross-validated.
Analytical Modeling and Maximum Power Point Tracking Control of Partially Shaded Photovoltaic Generation System

To adequately use array components of large-scale photovoltaic generation system, an analytical modeling with modified multidimensional configuration of partially shaded photovoltaic systems was designed, a concentrated maximum power point tracking(MPPT) controller was adopted and simulated in MATLAB environment. Simulation results show that, the analytical modeling with modified multidimensional configuration could optimize array component of large-scale photovoltaic generation system, save equipment and reduce cost. To improve the tracking accuracy and velocity, an improved particle swarm optimization(PSO) based maximum power point tracking method is proposed and corresponding modeling simulation and experiments are performed. Comparing performance index and output waveform of the proposed MPPT method with those from perturbation and observation(PO), it is validated that the improved PSO possesses faster tracking velocity for MPP and can avoid the oscillation around MPP.
Initialization and setup of the Coastal Model Test Bed : CSHORE

Abstract : The purpose of this Coastal and Hydraulics Engineering Technical Note (CHETN) is to introduce the Coastal Model Test Bed (CMTB) and the application of STWAVE. Numerical models are used by engineers, scientists, and coastal planners in U.S. Army Corps of Engineers Districts, U.S. Army Engineer Research and Development Center (ERDC), academia, and other public and private agencies to simulate complex scenarios at a reasonable cost. The CMTB has been initiated to evaluate and understand the strengths and weaknesses of numerical hydrodynamic and morphologic models using high-resolution temporal and spatial measurements at the Coastal and Hydraulics Laboratory (CHL) Field Research Facility (FRF) in Duck, NC. The improved evaluation methodology will promote rapid enhancement of model capability and focus research efforts in the coastal environment. The CMTB concept and initial setup methodology are described in this document.
Enhancing and Extending the Meta-Analytic Comparison of Newer Genre Leadership Forms

Interest in leadership research is growing, however, the rate of leadership learning is slowing down due to the proliferation of new leadership constructs. The objective of the present meta-analysis is to address the significant shortcomings in prior meta-analytic research on newer genre leadership forms by (a) utilizing a substantially greater number of studies and observations than in previous meta-analyses and (b) examining the meta-analytic correlations among the newer genre leadership forms. The results of the present study indicate that the newer genre leadership forms overlap to a greater degree than previously reported, while at the same time accounting for some degree of unique variance in the literature's most studied outcome variables; estimates of the relative contribution of each leadership form to the outcomes are provided, providing new insights into the distinctiveness of each leadership form. The findings suggest that pursuing an integrated theory and measure of newer genre leadership forms is a desirable future step for leadership research.
What and Where: Location-Dependent Feature Sensitivity as a Canonical Organizing Principle of the Visual System

Traditionally, functional representations in early visual areas are conceived as retinotopic maps preserving ego-centric spatial location information while ensuring that other stimulus features are uniformly represented for all locations in space. Recent results challenge this framework of relatively independent encoding of location and features in the early visual system, emphasizing location-dependent feature sensitivities that reflect specialization of cortical circuits for different locations in visual space. Here we review the evidence for such location-specific encoding including: (1) systematic variation of functional properties within conventional retinotopic maps in the cortex; (2) novel periodic retinotopic transforms that dramatically illustrate the tight linkage of feature sensitivity, spatial location, and cortical circuitry; and (3) retinotopic biases in cortical areas, and groups of areas, that have been defined by their functional specializations. We propose that location-dependent feature sensitivity is a fundamental organizing principle of the visual system that achieves efficient representation of positional regularities in visual experience, and reflects the evolutionary selection of sensory and motor circuits to optimally represent behaviorally relevant information. Future studies are necessary to discover mechanisms underlying joint encoding of location and functional information, how this relates to behavior, emerges during development, and varies across species.
HIV Capsid Protein Genetic Diversity Across HIV-1 Variants and Impact on New Capsid-Inhibitor Lenacapavir

The HIV p24 capsid protein has an essential, structural, and functional role in the viral replication cycle, being an interesting target for vaccine design, diagnostic tests, and new antiretroviral drugs (ARVs). The HIV-1 variability poses a challenge for the accuracy and efficiency of diagnostic and treatment tools. This study analyzes p24 diversity among HIV-1 variants and within its secondary structure in HIV-1 M, O, P, and N groups. All available HIV-1 p24 nucleotide sequences were downloaded from the Los Alamos HIV Sequence Database, selecting 23,671 sequences belonging to groups O, N, P, and M (9 subtypes, 7 sub-sub types, and 109 circulating recombinant forms or CRFs). Using a bioinformatics tool developed in our laboratory (EpiMolBio program), we analyzed the amino acid conservation compared to the HXB2 subtype B reference sequence and the V-markers, or amino acid changes that were specific for each variant with at least 10 available sequences. We inferred the p24 consensus sequence for HIV-1 and for each group to analyze the overall conservation in p24 main structural regions, reporting the percentage of substitutions per variant affecting the capsid assembly and molecule-binding, including those associated with resistance to the new capsid-inhibitor lenacapavir, and the key residues involved in lenacapavir-p24 interaction, according to the bibliography. Although the overall structure of p24 was highly conserved, the conservation in the secondary structure varied between HIV-1 variants and the type of secondary structure. All HIV-1 variants presented >80% amino acid conservation vs. HXB2 reference sequence, except for group M sub-subtype F1 (69.27%). Mutants affecting the capsid assembly or lenacapavir capsid-binding were found in <1% of the p24 consensus sequence. Our study reports the HIV-1 variants carrying 14 unique single V-markers in 9/38 group M variants and the level of p24 conservation in each secondary structure region among the 4 HIV-1 groups and group M variants, revealing no natural resistance to lenacapavir in any HIV-1 variant. We present a thorough analysis of p24 variability among all HIV-1 variants circulating to date. Since p24 genetic variability can impact the viral replication cycle and the efficacy of new p24-based diagnostic, therapeutic, and vaccine strategies, conservation studies must consider all HIV-1 variants circulating worldwide.
Economic development as a function of construction project performance

Poor performance of construction projects is one of the major cause for concern in the construction industry. Many of the construction projects executed in Nigeria experienced several challenges ranging from simple to complex issues. This paper therefore, examines factors affecting the performance of construction projects, their effects on the economic development and the impact of the factors on the economic development of the nation. The study identified a set of factors believed to affect project performance through extensive review of literature which form the basis for questionnaire survey. A total of 200 questionnaires were self-administered to professionals in the Nigerian construction industry, out of which 148 were retrieved and considered fit for analysis. The survey findings indicate that the most important factors affecting project performance are: project design cost, project complexity, unavailability of resources, quality of equipment and raw materials, while ontime completion, client satisfaction and productivity were considered to be the main measures of construction project performances. Improvement in technology and extension of infrastructures, were the most important indices of economic development. It is recommended that project owners must work collaboratively with all the professionals involved in carrying out construction project in order to facilitate good performance. More so, stakeholders in the construction industry including professionals and regulatory bodies should be proactive in discharging their responsibilities bearing in mind the effect of construction project performance on economic development of the country.
Temporal and Spatial Structure of Collective Pass-Chaining Action Performed by Japanese Top-Level Field Hockey Players

In real hockey or soccer games, scoring opportunities usually occur quite rarely, and thus, for most of the duration of a game, the ball is drifting between the two goals. This pass-chaining situation can be regarded as the stable state of the offense–defense interaction. In the current study, temporal and spatial structure of this dynamical state was unveiled via quantification of the “defensive pressure distribution” on the pass trajectory, which was modeled as a non-linear function of the distance between the defender(s) and a given position on the pitch. Two groups, i.e., a top-level group and a less-skilled group, of Japanese collegiate hockey players were asked to play in 3-on-3 small-sided games between players of the same skill levels. When both the top-level and less-skilled players succeeded in passing the ball, there were no skill-level differences observed in the defensive pressure distribution on the pass trajectory. In these cases, the defenders put a certain level of pressure on the middle of the pass trajectory when the passer received a previously released pass, and later, when he released the ball to a teammate, the defenders approached the position at which the passer released the ball to intensively press on the passer. However, in the cases wherein they failed to thread the ball, clear differences were observed between the groups in terms of the defensive pressure distribution on the pass trajectory. In particular, for the less-skilled group, extremely intensive defensive pressure was put on the overall regions of the pass trajectory heavily concentrated on the timing at which the passer released the pass. This unique pressure distribution emerged for the less-skilled group because of their long ball-keeping duration (longer than 1 s and also longer than that for the top-level group), i.e., from the moment the passer received the ball, to the moment he released it to the next attacker. Thus, for top-level hockey players, a short time constant (less than 1 s) for the passing action will enable the passers to avoid extremely intensive defensive pressure, and enable the emergence of a dynamically stable attack–defense deadlock state through continuous chaining of the pass.
Dual RNA-Seq of H5N1 Avian Influenza Virus and Host Cell Transcriptomes Reveals Novel Insights Into Host-Pathogen Cross Talk

H5N1 avian influenza virus (AIV) is a highly pathogenic influenza virus that poses a substantial threat to poultry production and public health. A comprehensive understanding of host–pathogen interactions for AIV requires knowledge of gene expression changes in both the pathogen and the host upon infection. We report the use of dual RNA sequencing technology to uncover trends in gene expression in H5N1 AIV and chickens (DF1 cells) during the course of infection. The expression of all viral genes increased continuously from 0 to 20 h post infection. We also identified 2,762 differentially expressed host genes during infection. Pathway analysis found that genes related to the signaling pathways of DNA replication, T cell activation, NF-kappa B signaling pathway, and RNA degradation were significantly enriched. We demonstrated that the cis-acting lncRNA MSTRG.14019. 1 targeted CSE1L and may affect virus replication. This study provides a more comprehensive and detailed understanding of host-virus interactions at the RNA level during the course of H5N1 AIV infection.
Updated Evaluation of Robotic- and Video-Assisted Thoracoscopic Lobectomy or Segmentectomy for Lung Cancer: A Systematic Review and Meta-Analysis

Objectives Robot-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) are the two principal minimally invasive surgical approaches for patients with lung cancer. This study aimed at comparing the long-term and short-term outcomes of RATS and VATS for lung cancer. Methods A comprehensive search for studies that compared RATS versus VATS for lung cancer published until November 31, 2021, was conducted. Data on perioperative outcomes and oncologic outcomes were subjected to meta-analysis. PubMed, Web of Science, and EMBASE were searched based on a defined search strategy to identify eligible studies before November 2021. Results Twenty-six studies comparing 45,733 patients (14,271 and 31,462 patients who underwent RATS and VATS, respectively) were included. The present meta-analysis showed that there were no significant differences in operative time, any complications, tumor size, chest drain duration, R0 resection rate, lymph station, 5-year overall survival, and recurrence rate. However, compared with the VATS group, the RATS group had less blood loss, a lower conversion rate to open, a shorter length of hospital stay, more lymph node dissection, and better 5-year disease-free survival. Conclusions RATS is a safe and feasible alternative to VATS for patients with lung cancer.