Miracle-dz/UniFAR-FTUs huggingface dataset:
Epilepsy and sudden unexpected death in epilepsy in a mouse model of human SCN1B-linked developmental and epileptic encephalopathy

Abstract Voltage-gated sodium channel β1 subunits are essential proteins that regulate excitability. They modulate sodium and potassium currents, function as cell adhesion molecules and regulate gene transcription following regulated intramembrane proteolysis. Biallelic pathogenic variants in SCN1B, encoding β1, are linked to developmental and epileptic encephalopathy 52, with clinical features overlapping Dravet syndrome. A recessive variant, SCN1B-c.265C>T, predicting SCN1B-p.R89C, was homozygous in two children of a non-consanguineous family. One child was diagnosed with Dravet syndrome, while the other had a milder phenotype. We identified an unrelated biallelic SCN1B-c.265C>T patient with a clinically more severe phenotype than Dravet syndrome. We used CRISPR/Cas9 to knock-in SCN1B-p.R89C to the mouse Scn1b locus (Scn1bR89/C89). We then rederived the line on the C57BL/6J background to allow comparisons between Scn1bR89/R89 and Scn1bC89/C89 littermates with Scn1b+/+ and Scn1b−/− mice, which are congenic on C57BL/6J, to determine whether the SCN1B-c.265C>T variant results in loss-of-function. Scn1bC89/C89 mice have normal body weights and ∼20% premature mortality, compared with severely reduced body weight and 100% mortality in Scn1b−/− mice. β1-p.R89C polypeptides are expressed in brain at comparable levels to wild type. In heterologous cells, β1-p.R89C localizes to the plasma membrane and undergoes regulated intramembrane proteolysis similar to wild type. Heterologous expression of β1-p.R89C results in sodium channel α subunit subtype specific effects on sodium current. mRNA abundance of Scn2a, Scn3a, Scn5a and Scn1b was increased in Scn1bC89/C89 somatosensory cortex, with no changes in Scn1a. In contrast, Scn1b−/− mouse somatosensory cortex is haploinsufficient for Scn1a, suggesting an additive mechanism for the severity of the null model via disrupted regulation of another Dravet syndrome gene. Scn1bC89/C89 mice are more susceptible to hyperthermia-induced seizures at post-natal Day 15 compared with Scn1bR89/R89 littermates. EEG recordings detected epileptic discharges in young adult Scn1bC89/C89 mice that coincided with convulsive seizures and myoclonic jerks. We compared seizure frequency and duration in a subset of adult Scn1bC89/C89 mice that had been exposed to hyperthermia at post-natal Day 15 versus a subset that were not hyperthermia exposed. No differences in spontaneous seizures were detected between groups. For both groups, the spontaneous seizure pattern was diurnal, occurring with higher frequency during the dark cycle. This work suggests that the SCN1B-c.265C>T variant does not result in complete loss-of-function. Scn1bC89/C89 mice more accurately model SCN1B-linked variants with incomplete loss-of-function compared with Scn1b−/− mice, which model complete loss-of-function, and thus add to our understanding of disease mechanisms as well as our ability to develop new therapeutic strategies.
Representation of Catchment Connectivity in Lumped Models

Hydrology models are widely used to simulate hydrology and generation and transport of constituents such as salt, phosphorus and nitrogen from catchments to streams. An increasing number of models use a lumped approach with catchment areas represented as sub-catchments based on their land use to avoid the complexity of spatially explicit models. However, most lumped models disregard the interaction between sub-catchments, their connectivity and its influence on nutrient export. Instead, run-off from different areas is often routed directly to the catchment outlet. The spatially explicit hydrological model THALES was used to simulate a theoretical catchment and the influence of explicitly considering the spatial distribution of constituents concentrations and its effect on the solute export. The modelling results show that the response of the surface and subsurface flows vary for different spatial arrangements due to interaction of the run-off and infiltration processes between the different land uses. These differences in response are not represented in lumped models that do not consider the interaction of flow paths between the different land use and this leads to an under or overestimation of the exported loads. Results highlight the importance of considering connectivity of pathways when modelling hydrology and nutrients response. It is also clear that lumped hydrological models must be applied with care if the interaction of flow paths between sub-catchments is not considered, especially if calibration data are not available. A possible solution to simulate effects of landscape position in the lumped catchment model E2 is briefly discussed.
Fine-tuning CRISPR/Cas9 gene editing in common bean (Phaseolus vulgaris L.) using a hairy root transformation system and in silico prediction models

The stable transformation of common bean is a challenging and time-consuming process. Although CRISPR/Cas9 has revolutionized gene editing with its high efficiency and specificity, the performance of the system can be affected by multiple factors, such as sgRNA specificity and effectiveness, and the choice of promoter used to drive Cas9 expression. The use of a hairy root transformation system to initially check the efficiency of sgRNAs and the impact of different promoters could speed up this process and increase the chances of success. We initially tested three different transformation methods to induce hairy roots and selected a preferred method suitable for a variety of different common bean genotypes. This method involved inoculating a severed radicle with Rhizobium rhizogenes K599 and was fast, had a high transformation frequency of 42-48%, and resulted in numerous hairy roots. This method was further used for the transformation of explants using R. rhizogenes harboring different CRISPR/Cas9 constructs and evaluated the on-target activity of sgRNAs targeting raffinose family oligosaccharides biosynthetic genes and the impact of different promoters driving Cas9 on the gene editing efficiency. Additionally, we evaluated the reliability of the in silico tools, CRISPOR, CRISPR RGEN, and inDelphi to predict the sgRNA efficiencies and resulting mutations. Our results showed that the hairy root transformation system allows for rapid evaluation of multiple sgRNAs and promoters. We also identified several highly efficient sgRNAs that induced frameshift mutations at rates of up to 70% when a parsley ubiquitin promoter was driving Cas9 expression, providing valuable information for the selection of the most effective sgRNAs and promoters for future transformation experiments. Although most of the computational models used to predict the sgRNA efficiency did not match the in planta results, the Lindel model proved to be the most reliable for P. vulgaris, accurately predicting the sgRNA efficiency and the type of induced mutation in most hairy roots. Furthermore, the inDelphi algorithm could correctly predict deletions and single nucleotide insertions resulting from DNA double-strand breaks in common bean. These results offer promising implications for enhancing precise editing in plants because they provide the possibility of predicting repair outcomes.
Optimal Selfish Mining-Based Denial-of-Service Attack

In recent years, Bitcoin has become one of the most popular cryptocurrencies. The most significant mechanism of Bitcoin is PoW (Proof-of-Work), but it also brings opportunities for mining attacks. In our last study, we proposed a Selfish Mining-based Denial-of-Service Attack (SDoS), which can cause serious threats to the Bitcoin system. On this basis, we further put forward three greedier SDoS attack strategies: a competitive greedy SDoS attack strategy ESDoS, a trail greedy SDoS attack strategy TSDoS, a hybrid greedy SDoS attack strategy ETSDoS, and a more public SDoS attack strategy PSDoS. Besides, we also study the adversary’s optimal strategies under different conditions. The experimental results show that if the adversary adopts the SDoS optimal strategy, his revenue increase rate will be further improved and significantly higher than the other existing mining attacks. If the adversary masters 14% of the total mining power, he has a chance to improve his revenue (25% in Selfish Mining, 19.6% in SDoS), and if the adversary masters 15% of the total mining power, he is capable of launching a 51% attack.
REMOTE SENSING (RS), GEOGRAPHIC INFORMATION SYSTEM (GIS) AND CELLULAR AUTOMATA MODEL (CA) AS TOOLS FOR THE SIMULATION OF URBAN LAND USE CHANGE- A CASE STUDY OF SHAHR-E-KORD

This research is committed to providing methodological guidelines for the simulation of urban land use dynamics using GIS, RS and CA models. Urban-CA modeling experiments have been conducted for a medium-sized city (Shahr-e-Kord) in Iran over a thirty-five year time span. Global transition probabilities obtained from the Markov chain model and Unique Conditions Map were derived from WoE. Local transition probabilities were estimated using infrastructural factors by two different probabilistic empirical methods: the WoE approach, based on Bayesian theory; and logistic regression. The final land use transition rules drove an Urban-CA model, built upon basis of stochastic land use allocation algorithms. These Urban-CA models drive a CA model based on eight cell Moore neighborhoods. The simulation outputs were statistically validated according to a new compound method based on a Multiple Resolution Model (MRM). After achieving simulations for the 1999-2002 and 20022006 time periods along the whole time series, forecast simulations were carried out up to 2025 (1404) and for various urban planning scenarios. For all simulation periods, the best results were obtained from a combined Markov chain and logistic regression with 0.5 Gama to derive the transition rules. Different simulation outputs for the case study indicate their possible further applicability for generating simulation of growth trends both for Iranian cities and cities world-wide.
New aspects of coffee processing : How do the different post harvest treatments influence the formation of potential flavour precursors ?

This paper represents a brief overview on coffee processing with special emphasis on the physiology and biochemistry of the coffee beans. Green coffee is obtained by submitting the harvested coffee cherries to either wet or dry processing. It is well accepted that wet processed coffees evolve much better quality. The decisive quality criterion of coffee as a beverage is its aroma, being composed of more than 800 compounds. Surprisingly, only about 30 of these contribute significantly to the specific coffee aroma. These aroma impact compounds are suitable indicators to estimate objectively the aroma differences resulting from different processing. Up to now, the reasons for the quality differences of technologically distinctively produced coffees are unknown. In this context, the biochemical and physiological processes which occur in the living coffee bean during post harvest processing, and which are related to quality, must be taken into consideration. The coffee plant reveals some particularities which are relevant for the generation of aroma components but which, so far, hardly any attention has been paid to: the coffee bean stands intermediately between recalcitrant and orthodox seeds. It does not undergo a resting period induced by maturation drying, and seed germination is initiated while the fruit is still in the final stages of development. In consequence, coffee beans that are submitted to processing do not represent resting seeds but rather developing seedlings. Substantial features of a seed in state of germination are an increasing rate of respiration and the mobilization of storage compounds. These physiological processes must have an impact on the concentration of aroma precursors in green coffee beans and thus on coffee quality. Accordingly, the reported discrepancies between differently processed coffees appear to be the consequence of distinct developmental stages in the course of the coffee seed germination, since the different processing procedures (dry or wet) are suitable to favour germination to an unequal extent.
Distribution of surface sediment types and sedimentary environment divisions in the northern South China Sea

A total of 224 surface sediment samples collected from the northern South China Sea were studied in terms of grain size and carbonate content, to understand the sediment transport patterns and the corresponding depositional environments in the region. Results revealed that sediments in the study area could be divided into the following types:gravelly sand, coarse sand, medium sand, fine sand, silty sand, sandy silt, sand-silt-clay, clayey silt, silty clay, and clay.The abyssal-bathyal sediments could be divided into eight types, namely, siliceous clay, calcareous clay, calcareous and siliceous clay, foraminifer ooze, calcareous clayey silt, calcareous sand-silt-clay, and siliceous clayey silt. Among them,the silty clay, clayey silt, sand, sandy silt, and clay are the major types, accounting for more than 80% of the area total.Factor analysis of grain size parameters and carbonate content was used to discriminate different depositional environments. Results showed that the above parameters may be divided into three types and the study area could then be divided into four subareas. The factor 1 acts on subareasⅠ and Ⅱ. Clayey sediments are distributed in subarea Ⅰ,which is mainly located in the deep waters in the southeast. The medium and fine sand zones are distributed in subareaⅡ, which normally occurs on the outer continental shelf off the west of Guangdong Province and the offshore areaalong the coast of South China. The factor 2 acts on subarea Ⅲ, where silt of coarse and medium sizes is mainly distributed on the slope in the southeast off Hainan island and off the Pearl River Estuary, and on the outer shelf southwest off Taiwan. The factor 3 acts on subarea Ⅳ, where coarse sand is mainly distributed on the inner continental shelf southwest of Taiwan.
Electrode Effect on Ferroelectricity in Free-Standing Membranes of PbZr0.2Ti0.8O3

We report the effects of screening capacity, surface roughness, and interfacial epitaxy of the bottom electrodes on the polarization switching, domain wall (DW) roughness, and ferroelectric Curie temperature (TC) of PbZr0.2Ti0. 8O3 (PZT)-based free-standing membranes. Singe crystalline 10–50 nm (001) PZT and PZT/La0.67Sr0. 33MnO3 (LSMO) membranes are prepared on Au, correlated oxide LSMO, and two-dimensional (2D) semiconductor MoS2 base layers. Switching the polarization of PZT yields nonvolatile current modulation in the MoS2 channel at room temperature, with an on/off ratio of up to 2 × 105 and no apparent decay for more than 3 days. Piezoresponse force microscopy studies show that the coercive field Ec for the PZT membranes varies from 0.75 to 3.0 MV cm–1 on different base layers and exhibits strong polarization asymmetry. The PZT/LSMO membranes exhibit significantly smaller Ec, with the samples transferred on LSMO showing symmetric Ec of about −0.26/+0.28 MV cm–1, smaller than that of epitaxial PZT films. The DW roughness exponent ζ points to 2D random bond disorder dominated DW roughening (ζ = 0.31) at room temperature. Upon thermal quench at progressively higher temperatures, ζ values for PZT membranes on Au and LSMO approach the theoretical value for 1D random bond disorder (ζ = 2/3), while samples on MoS2 exhibits thermal roughening (ζ = 1/2). The PZT membranes on Au, LSMO, and MoS2 show TC of about 763 ± 12, 725 ± 25, and 588 ± 12 °C, respectively, well exceeding the bulk value. Our study reveals the complex interplay between the electrostatic and mechanical boundary conditions in determining ferroelectricity in free-standing PZT membranes, providing important material parameters for the functional design of PZT-based flexible nanoelectronics.
Calcareous nannofossil and foraminifer biostratigraphy of the Campanian–Maastrichtian chalk of the Femern Bælt (Denmark–Germany).

A new study based on calcareous nannofossil and benthic and planktonic foraminifer biostratigraphy is presented for the upper Campanian – Maastrichtian chalk of the Femern Baelt (Denmark and Germany; Fig.1). The results are consistent with recent studies of the Danish chalk for this interval, allowing correlation across the Danish Basin and forming the basis for correlation further afield within the Boreal Realm. Numerous studies have been carried out recently on the upper Campanian – Maastrichtian chalk of the Danish Basin, covering aspects such as sedimentology, depositional environment, macrofossil biostratigraphy, carbon isotope stratigraphy as well as nannofossil and dinoflagellate biostratigraphy. However, very few published studies on foraminifers exist across this interval in this area. The 09.A. 006, 09.A. 007 and 09.A. 008 boreholes (Fig. 2) were drilled in 2009 in preparation for construction of a fixed link across the Femern Baelt, which will connect Denmark to Germany (Ramboll Arup JV 2011). The boreholes penetrated glacial till, Paleocene–Eocene clay and chalk (Sheldon et al. 2012). Here, for the first time, the Boreal foraminifer biostratigraphy of the late Campanian – Maastrichtian interval is investigated and presented alongside nannofossil biostratigraphy. Geological setting and palaeogeography
AoI-Aware User Service Satisfaction Enhancement in Digital Twin-Empowered Edge Computing

—The emerging digital twin technique enhances the network management efficiency and provides comprehensive insights on network performance, through mapping physical objects to their digital twins. The user satisfaction on digital twin-enabled service relies on the freshness of digital twin data, which is measured by the Age of Information (AoI). Due to long service delays, the use of the remote cloud for delay-sensitive service provisioning faces serious challenges. Mobile Edge Computing (MEC), as an ideal paradigm for delay-sensitive services, is able to realize real-time data communication between physical objects and their digital twins at the network edge. However, the mobility of physical objects and dynamics of user query arrivals make seamless service provisioning in MEC become challenging. In this paper, we investigate dynamic digital twin placements for improving user service satisfaction in MEC environments, by introducing a novel metric to measure user service satisfaction based on the AoI concept and formulating two user service satisfaction enhancement problems: the static and dynamic utility maximization problems under static and dynamic digital twin placement schemes. To this end, we first formulate
Changes of ecosystem service value in Anhui Province and prediction of its changing trend

In order to analyze the effects of the change of land use type on ecosystem service value in Anhui Province,the ecological service value of Anhui province and five natural areas was calculated in 2000,2005 and 2010 based on dynamic data of the land use of Anhui province. Costanza calculation method of the ecosystem services value was used as reference. And coefficient of per unit area ecosystem service value of ecological system in Anhui was adopted. Grey forecasting model was established to predict the developmental trend of ecosystem services value. The results showed that the change of ecological service value was roughly an inverted"V"type in recent 10 years in Anhui Province. The ecological value had increased by 15 469 billion yuan from 2000 to 2005,but it had decreased by 2 531 billion yuan from 2005 to 2010. Using the prediction results of land use type to calculate the change of ecosystem service value from 2010 to2020,it will decline from 249 730 billion yuan in 2010 to 234 865 billion yuan in 2020,with a drop of 5. 96%. With the mass decrease of cultivated land and grassland,and the annual increase of construction land,the ecological pressure had become heavier and ecosystem service value tended to fall in recent ten years. In order to build a good ecological environment for sustainable and harmonious development of Anhui Province,we should adjust and optimize the land use structure,establish a dynamic ecological compensation mechanism and keep a reasonable population growth.
Temporal enzymatic treatment to enhance the remodelling of multiple cartilage microtissues into a structurally organised tissue

Scaffold-free tissue engineering strategies aim to recapitulate key aspects of normal developmental processes as a means of generating highly biomimetic grafts. Cartilage and fibrocartilaginous tissues have successfully been engineered by bringing together large numbers of cells, cellular aggregates or microtissues and allowing them to self-assemble or self-organize into a functional graft. Despite the promise of such approaches, considerable challenges still remain, such as engineering scaled-up tissues with predefined geometries, ensuring robust fusion between adjacent cellular aggregates or microtissues, and directing the (re)modelling of such biological building blocks into a unified scaled-up graft with hierarchical matrix organisation mimetic of the native tissue. In this study, we first demonstrate the benefits of engineering cartilage via the fusion of multiple cartilage microtissues compared to conventional scaffold-free approaches where (millions of) individual cells are allowed to aggregate and generate a cartilaginous graft. Key advantages include the engineering of a tissue with a richer extracellular matrix, a more hyaline-like cartilage phenotype and a final graft which better matched the intended geometry. A major drawback associated with this approach is that individual microtissues did not completely (re)model and remnants of their initial architectures where still evident throughout the macrotissue. In an attempt to address this limitation, the enzyme chondroitinase ABC (cABC) was employed to accelerate structural (re)modelling of the engineered tissue. Temporal enzymatic treatment supported robust fusion between adjacent microtissues, enhanced microtissue (re)modelling and supported the development of a more biomimetic tissue with a zonally organised collagen architecture. Additionally, we observed that cABC treatment modulated matrix composition (rebalancing the collagen:glycosaminoglycans ratio), tissue phenotype, and to a lesser extent, tissue mechanics. Ultimately, this work demonstrates that microtissue self-organisation is an effective method for engineering scaled-up cartilage grafts with a pre-defined geometry and near-native levels of ECM accumulation. Importantly we have demonstrated that key limitations associated with tissue engineering using multiple cellular aggregates, microtissues or organoids can be alleviated by temporal enzymatic treatment during graft development.
Characteristic Analysis on Sunshine Duration Change in Jiuquan Oasis in Recent 45 Years

Based on the monthly sunshine duration-data at 6 meteorological stations in Jiuquan oasis from 1960 to 2004,the sunshine duration-is-analyzed by calculating climate trend coefficient,climate tendency rate,-spatial interpolation method and-wavelet analysis.The results show that: In recent 45 years,the annual sunshine duration decreased with a tendency of 11.48-hours per ten years.There is obvious seasonal difference in sunshine duration.In addition to the performance of the spring sunshine duration appear the increasing trend,the tendency of annual sunshine duration in other seasons decreases mostly in varying degrees,especially in fall,followed by summer and winter.From 1960s to 1980s,the sunshine duration appear a significant decreasing trend with tendency of 2.5-hours per ten years,while in 1990s,the sunshine durations appear a significant increasing trend.From the sunshine duration wavelet analysis in Jiuquan oasis,there is a quasi-5~7 year oscillation cycles in sunshine duration (passing the 90% confidence level).