Miracle-dz/UniFAR-FTUs huggingface dataset:
PEXEL is a proteolytic maturation site for both exported and non-exported Plasmodium proteins

Obligate intracellular malaria parasites dramatically remodel their erythrocyte host through effector protein export to create a niche for survival. Most exported proteins contain a pentameric Plasmodium export element (PEXEL)/Host Targeting Motif that is cleaved in the parasite ER by the aspartic protease Plasmepsin V (PMV). This processing event exposes a mature N-terminus required for translocation into the host cell and is not known to occur in non-exported proteins. Here we report that the non-exported parasitophorous vacuole protein UIS2 contains a bona fide PEXEL motif that is processed in the P. falciparum blood-stage. While the N-termini of exported proteins containing the PEXEL and immediately downstream ∼10 residues is sufficient to mediate translocation into the RBC, the equivalent UIS2 N-terminus does not promote export of a reporter. Curiously, the UIS2 PEXEL contains an unusual aspartic acid at the fourth position which constitutes the extreme N-terminal residue following PEXEL cleavage (P1’, RILτDE). Using a series of chimeric reporter fusions, we show that Asp at P1’ is permissive for PMV processing but abrogates export. Moreover, mutation of this single UIS2 residue to alanine enables export, reinforcing that the mature N-terminus mediates export, not PEXEL processing per se. Prompted by this observation, we further show that PEXEL sequences in the N-termini of other non-exported rhoptry proteins are also processed, suggesting that PMV may be a more general secretory maturase than previously appreciated, similar to orthologs in related apicomplexans. Our findings provide new insight into the unique N-terminal constraints that mark proteins for export. Importance Host erythrocyte remodeling by malaria parasite exported effector proteins is critical to parasite survival and disease pathogenesis. In the deadliest malaria parasite Plasmodium falciparum, most exported proteins undergo proteolytic maturation via recognition of the pentameric Plasmodium export element (PEXEL)/Host Targeting motif by the aspartic protease Plasmepsin V (PMV) which exposes a mature N-terminus that is conducive for export into the erythrocyte host cell. While PEXEL processing is considered a unique mark of exported proteins, we demonstrate PEXEL motifs are present and processed in non-exported proteins. Importantly, we show that specific residues at the variable fourth position of the PEXEL motif inhibit export despite being permissive for processing by PMV, reinforcing that features of the mature N-terminus, and not PEXEL cleavage, identify cargo for export cargo. This opens the door to further inquiry into the nature and evolution of the PEXEL motif.
Specialized mesenteric lymphatic capillaries by-pass the mesenteric lymph node chain to transport peritoneal antigens directly into mediastinal lymph nodes

Lymphatic vessels (LVs) are indispensable for tissue fluid homeostasis and immune cell trafficking. The network of LVs that channel fluids from the gut into mesenteric lymph nodes (MLN) has been recognized as the sole lymphatic system in the mesentery. Here we describe an alternative, functionally autonomous set of capillary mesenteric LVs (capMLVs) that by-pass the MLNs and drain directly into mediastinal LNs. CapMLVs develop perinatally from valves of collective mesenteric lymphatic vessels (colMLVs) in response to arterial endothelial cell-derived VEGF-C. Once extended, capMLVs detach from colMLVs to form an independent elongated network comprised of LYVE1+, CCL21+ endothelial cells. Avascular areas of the mesentery juxtaposed to capMLVs contain cell islets that express ACKR4. This CCL21-scavenging atypical receptor facilitates the migration of mesenteric phagocytes into capMLVs to be channeled directly into mediastinal LNs. This allows peritoneum-derived ominous antigens to be processed separately from alimentary antigens.
How climate change and population growth will shape attendance and human-wildlife interactions at British Columbia parks

Protected areas are important for ecological conservation while simultaneously supporting culturally, and economically valuable tourism. However, excessive guest volumes strain operations and risk human-wildlife conflict, threatening the sustainability of nature-based tourism. Thus, park managers need to know what factors underpin attendance and how these might interact to shape future attendance. Using a decade of attendance records from 249 provincial parks, in British Columbia (BC), Canada, as well as 12 years of human-wildlife interactions (HWI) records at five national parks in BC, we modelled the impacts of weather conditions and population growth interact on park attendance and HWIs. We paired these models with climate change and population growth scenarios to generate projections of how attendance and HWIs will change throughout the century. Climate change is projected to result in more precipitation and higher temperatures, and, over this same time span, BC’s population is expected to grow substantially. Based on the observed relationship between attendance and weather, parks should anticipate a marked rise in visitors and HWIs especially during their respective peak seasons. These projections provide park managers with the information required for proactive management, ultimately contributing to the sustainability of recreation and tourism in protected areas.
Simulation of Magnetic Phenomena at Realistic Interfaces

Simulation of Magnetic Phenomena at Realistic Interfaces Sergiy Grytsyuk In modern technology exciting developments are related to the ability to understand and control interfaces. Particularly, magnetic interfaces revealing spindependent electron transport are of great interest for modern spintronic devices, such as random access memories and logic devices. From the technological point of view, spintronic devices based on magnetic interfaces enable manipulation of the magnetism via an electric field. Such ability is a result of the different quantum effects arising from the magnetic interfaces (for example, spin transfer torque or spin-orbit torque) and it can reduce the energy consumption as compared to the traditional semiconductor electronic devices. Despite many appealing characteristics of these materials, fundamental understanding of their microscopic properties and related phenomena needs to be established by thorough investigation. In this work we implement firstprinciples calculations in order to study the structural, electric, and magnetic properties as well as related phenomena of two types of interfaces with large potential in spintronic applications: 1) interfaces between antiferromagnetic 3d-metal-oxides and ferromagnetic 3d-metals and 2) interfaces between non-magnetic 5d(4d)and ferromagnetic 3d-metals. A major difficulty in studying such interfaces theoretically is the typically large lattice mismatch. By employing supercells with Moiré patterns, we 5 eliminate the artificial strain that leads to doubtful results and are able to describe the dependence of the atomic density at the interfaces on the component materials and their thicknesses. After establishing understanding about the interface structures, we investigate the electronic and magnetic properties. A Moiré supercell with transition layer is found to reproduce the main experimental findings and thus turns out to be the appropriate model for simulating magnetic misfit interfaces. In addition, we systematically study the magnetic anisotropy and Rashba band splitting at non-magnetic 5d(4d)and ferromagnetic 3d-metal interfaces and their dependences on aspects such as interdiffusion, surface oxidation, thin film thickness and lattice mismatch. We find that changes of structural details strongly alter the electronic states, which in turn influences the magnetic properties and phenomena related to spin-orbit coupling. Since the interfaces studied in this work have complex electronic structures, a computational approach has been developed in order to estimate the strength of the Rashba band splitting below and at the Fermi level. We apply this approach to the interfaces between a Co monolayer and 4d (Tc, Ru, Rh, Pd, and Ag) or 5d (Re, Os, Ir, Pt, and Au) transition metals and find a clear correlation between the overall size of the band splitting and the charge transfer between the d-orbitals at the interface. Furthermore, we show that the spin splitting at the Fermi surface scales with the induced orbital moment weighted by the strength of the spin-orbit coupling.
FAST: a fast and scalable factor analysis for spatially aware dimension reduction of multi-section spatial transcriptomics data

Biological techniques for spatially resolved transcriptomics (SRT) have advanced rapidly in both throughput and spatial resolution for a single spatial location. This progress necessitates the development of efficient and scalable spatial dimension reduction methods that can handle large-scale SRT data from multiple sections. Here, we developed FAST as a fast and efficient generalized probabilistic factor analysis for spatially aware dimension reduction, which simultaneously accounts for the count nature of SRT data and extracts a low-dimensional representation of SRT data across multiple sections, while preserving biological effects with consideration of spatial smoothness among nearby locations. Compared with existing methods, FAST uniquely models the count data across multiple sections while using a local spatial dependence with scalable computational complexity. Using both simulated and real datasets, we demonstrated the improved correlation between FAST estimated embeddings and annotated cell/domain types. Furthermore, FAST exhibits remarkable speed, with only FAST being applicable to analyze a mouse embryo Stereo-seq dataset with >2.3 million locations in only 2 hours. More importantly, FAST identified the differential activities of immune-related transcription factors between tumor and non-tumor clusters and also predicted a carcinogenesis factor CCNH as the upstream regulator of differentially expressed genes in a breast cancer Xenium dataset.
Core enhancers of the 3’RR optimize IgH nuclear position and loop conformation for oriented CSR

Class switch recombination is an essential process which enabling B cells to adapt immunoglobulin subtypes to antigens. Transcription plays a crucial role in regulating CSR in which the IgH 3’Regulatory Region (3’RR) was identified as a key player. The 3’RR stands at the 3’ end of IgH locus and is composed of four core enhancers surrounded by inverted repeated sequences, forming a quasi-palindrome. In addition to transcriptional control, nuclear organization appears to be an important level in CSR regulation. Furthermore, the chromatin loops at IgH locus facilitate an efficient CSR recombination by bringing the donor and acceptor switch regions closer together. However, the precise control mechanisms governing both of these processes remain partially understood. Here, using the reference DNA 3D-FISH technique combined with various high throughput approaches, we showed that 3’RR core enhancers are necessary and sufficient to preorganize resting B cell nuclei to facilitate a deletional CSR mechanism at activated stage. We demonstrated that the 3’RR core enhancers regulate IgH locus addressing in the nuclei, control IgH locus accessibility and orchestrate IgH loops formation. Our findings pinpointed an additional regulation level of mechanisms underlying B cell diversification. Graphical abstract Position of IgH loci through B cell development (from transitional to stimulated stages) is represented by the red spots. In wt and c3’RR context, IgH loci get closer from each other and from nucleus center during evolution from transitional to mature resting stage and they relocates more at nuclear periphery, away one from each other, upon in vitro stimulation. In Δ3’RR model, this dynamic is lost and, moreover, IgH loci are more localized to pericentromeric heterochromatin (represented by green area) since the mature resting B cell stage and remain in after in vitro stimulation.
An expanded genetic toolbox to accelerate the creation of Acholeplasma laidlawii driven by synthetic genomes

Assembling synthetic bacterial genomes in yeast and genome transplantation has enabled an unmatched level of bacterial strain engineering, giving rise to cells with minimal and chemically synthetic genomes. However, this technology is currently limited to members of the Spiroplasma phylogenetic group, mostly Mycoplasmas, within the Mollicute class. Here, we propose new genetic tools for developing these technologies for Acholeplasma laidlawii, which is phylogenetically distant from Mycoplasmas and, unlike most Mollicutes, uses a standard genetic code. We first investigated a donor-recipient relationship between two A. laidlawii strains through whole-genome sequencing. We then created multi-host shuttle plasmids and used them to optimize an electroporation protocol. We also demonstrated the use of evolution to create superior strains for DNA uptake via electroporation. For genome transplantation, we selected A. laidlawii 8195 as the recipient strain and created a PG-8A donor strain by inserting a Tn5 transposon carrying a tetracycline resistance gene. The tools presented here will improve Acholeplasma research and accelerate the effort toward creating A. laidlawii strains driven by synthetic genomes. Graphical Abstract
Gene expression variation underlying tissue-specific responses to copper stress in Drosophila melanogaster

Copper is one of a handful of biologically necessary heavy metals that is also a common environmental pollutant. Under normal conditions, copper ions are required for many key physiological processes. However, in excess, copper quickly results in cell and tissue damage that can range in severity from temporary injury to permanent neurological damage. Because of its biological relevance, and because many conserved copper-responsive genes also respond to other non-essential heavy metal pollutants, copper resistance in Drosophila melanogaster is a useful model system with which to investigate the genetic control of the response to heavy metal stress. Because heavy metal toxicity has the potential to differently impact specific tissues, we genetically characterized the control of the gene expression response to copper stress in a tissue- specific manner in this study. We assessed the copper stress response in head and gut tissue of 96 inbred strains from the Drosophila Synthetic Population Resource (DSPR) using a combination of differential expression analysis and expression quantitative trait locus (eQTL) mapping. Differential expression analysis revealed clear patterns of tissue-specific expression, primarily driven by a more pronounced gene expression response in gut tissue. eQTL mapping of gene expression under control and copper conditions as well as for the change in gene expression following copper exposure (copper response eQTL) revealed hundreds of genes with tissue- specific local cis-eQTL and many distant trans-eQTL. eQTL associated with MtnA, Mdr49, Mdr50, and Sod3 exhibited genotype by environment effects on gene expression under copper stress, illuminating several tissue- and treatment-specific patterns of gene expression control. Together, our data build a nuanced description of the roles and interactions between allelic and expression variation in copper-responsive genes, provide valuable insight into the genomic architecture of susceptibility to metal toxicity, and highlight many candidate genes for future functional characterization.
Simulation of the blooming phenomenon in forced circular jets

The bifurcation and the blooming of jets have been numerically investigated at moderate Reynolds numbers. The study is motivated by a review article of Reynolds et al. (Annu. Rev. Fluid Mech., vol. 35, 2003, pp. 295–315) in which flow visualization images of jet blooming have been discussed, when the flow is subjected to inflow perturbations. Dual-mode perturbation, a combination of axisymmetric and helical excitations, has been used at the inflow plane to control the jet structures. In addition to the excitation frequency ratio, the effects of small-scale perturbation, excitation amplitude and initial momentum thickness have been examined. Results obtained at a Reynolds number of 2000 show that the number of branches formed in the blooming jet is strongly dependent on the excitation frequency ratio. For frequency ratios of 2, 2.5, 2.25, 2.4 and 2.22, the number of branches seen is 2, 5, 9, 12 and 20 respectively. In a blooming jet, the offset angle lies in the range 140°–180°. An equal number of branches is seen in the time-averaged flow field as well. The range of excitation frequency of the axisymmetric mode of perturbation is found to be $0.45<\mathit{St}_{D}<0.525$ , with an excitation frequency ratio range of $2<R_{f}<2.6$ , for which blooming jets are formed. The role of inlet shear layer thickness is less important as far as the blooming jet is concerned, while increasing excitation amplitude increases entrainment. Time-averaged data show that the blooming patterns persist in time, showing a substantial increase in spreading and entrainment.
Verification of MIKE 11-NAM Model for runoff modeling using ANN, FIS, and ARIMA methods in poorly studied basin

Hydrological information is the basis for conducting water balance studies in any region, and surface runoff is one of the most important hydrological parameters and one of the most difficult in the process of estimation and prediction. This study aims to verification of the MIKE 11-NAM Model for runoff modeling using artificial neural network (ANN), fuzzy inference system (FIS), and autoregressive integrated moving average (ARIMA) methods at Al-Jawadiyah hydrometric station on the Orontes River in Syria. MATLAB was used to build neural and fuzzy models, where many models were built with the change in all parameters, functions, and algorithms that can be used, and the Minitab was used to build ARIMA models. Many models were prepared with the addition of seasonal effect, and the comparison results showed an advantage for artificial neural network models in terms of evaluation parameters. After that, the artificial neural network models were adopted in the process of filling the gaps in the time series of surface runoff in the study area to be used in the Mike program for modeling the runoff and through the method of trial and error with a high number of iterative cycles, model parameters were calculated and runoff values estimated. Still, the results were not good, and there were significant differences between the measured values and the values simulated by the model, and this is due to the significant lack of available data. This study recommends the use of artificial intelligence and machine learning models in the field of estimation and prediction of hydrological parameters.
Systematic Review Interest of pharyngeal packing in head and neck surgery: a meta-analysis

-- Introduction: There is controversy regarding the use of pharyngeal packing in oral and nasal surgery. The primary objective of this study was to examine the association between pharyngeal packing, throat pain, and postoperative nausea and vomiting (PONV) in head and neck surgery. Material and methods: A systematic review of clinical studies published from January 2000 to August 2020 concerning the use of pharyngeal packing in head and neck surgery was conducted in the Medline, ScienceDirect and Cochrane Library databases. Throat pain and PONV were collected in each article, and a meta-analysis was performed. Results: A total of 10 clinical trials involving 877 patients were included in the meta-analysis. Pharyngeal packing did not signi ﬁ cantly decrease PONV score either during the immediate (OR =0.90, 95% CI: 0.59 to 1.38, p =0.52, I 2 =0%) or the delayed postoperative period (OR =0.88, 95% CI: 0.54 to 1.43, p =0.28, I 2 =21%), but signi ﬁ cantly increased the immediate postoperative throat pain score (MD=0.68, 95% CI: 0.21 to 1.16, p = 0.19, I 2 =35%). Conclusion: This study suggests that the use of a pharyngeal packing to improve the preoperative aftermath in head and neck surgery should not be recommended.
Three Machines Flowshop Scheduling Model with Bicriterion Objective Function

Objectives: To find the optimum solution for minimization of bicriterion (makespan, weighted mean flowtime) objective function of three machines flowshop scheduling problem with transportation times and weight of the jobs. Methods/Statistical Analysis: In this paper, we used two types of methodologies first one is based on a Branch and Bound (BB we developed a new heuristic algorithm using Palmer approach for obtaining the optimal or near optimal sequence to minimize the bicriterion objective function of three machines scheduling problem in flowshop environments with transportation times and weights of the jobs. Comparative study between both the proposed algorithms is also considered to select the best methodology of our bicriterion objective function with the help of numerical illustration. Directed graphs, Gantt chart and Branch Tree are also generated to understand the process of lower bound and effectiveness of proposed algorithms. Findings: We solved the same numerical by constructed Branch & Bound (B&B) algorithm and Palmer based heuristic algorithm. Hence, comparatative result show that our originated B&B algorithm gives the optimal solution or better result as compare to Palmer based heuristic algorithm for minimization of bicriterion (makespan and weighted mean flowtime) objective function. We also calculated the percentage improvement of our constructive B&B algorithm over palmer based new heuristic algorithm and it is examined that constructive B&B algorithm gives the 8.33% improvement in make span and 6.52% improvement in weighted mean flowtime. The directed graph of each computational level is also originated to understand the computational process of the lower bounds easily. The Gantt chart between both the proposed algorithms is also generated to verify the effectiveness of new originated B&B algorithm. Directed graph is also generated of the optimal sequence. Finally, Branch Tree is generated to empathize the process of Lower Bound. Application/Improvements: Our constructed B&B algorithm provide an important tool for decision maker to minimize the makespan and weighted mean flowtime together as bicriterion objective function of three machine flowshop scheduling problems.
Toward an Operational Water Cycle Prediction System for the Great Lakes and St. Lawrence River

AbstractIn this time of a changing climate, it is important to know whether lake levels will rise, potentially causing flooding, or river flows will dry up during abnormally dry weather. The Great Lakes region is the largest freshwater lake system in the world. Moreover, agriculture, industry, commerce, and shipping are active in this densely populated region. Environment and Climate Change Canada (ECCC) recently implemented the Water Cycle Prediction System (WCPS) over the Great Lakes and St. Lawrence River watershed (WCPS-GLS version 1.0) following a decade of research and development. WCPS, a network of linked models, simulates the complete water cycle, following water as it moves from the atmosphere to the surface, through the river network and into lakes, and back to the atmosphere. Information concerning the water cycle is passed between the models. WCPS is the first short-to-medium-range prediction system of the complete water cycle to be run on an operational basis anywhere. It currently produces .