Miracle-dz/UniFAR-FTUs huggingface dataset:
Multifactorial approach is needed to unravel the maturation phases of human neurons derived from induced pluripotent stem cells

Neurons derived from induced pluripotent stem cells (h-iPSC-Ns) provide an invaluable model for studying the physiological aspects of neuronal development and diseases. However, multiple studies have also demonstrated that h-iPSC-Ns exhibit a high degree of functional and epigenetic diversity. Due to the imprecise characterization and significant variation among the currently available maturation protocols, it is essential to establish a set of criteria to standardize models and accurately characterize and define the developmental properties of neurons derived from iPSCs. In this study, we conducted a comprehensive analysis of the h-iPSC-Ns via electrophysiological and microscopic techniques to follow their functional development at the cellular and network levels. This enabled us to provide a thorough description of the maturation process of h-iPSC-Ns over a 10-week period in vitro. Specifically, we have used conventional whole-cell patch-clamp and dynamic clamp techniques, alongside morphometry, to assess the characteristics of maturing h-iPSC-Ns. Additionally, we utilized calcium imaging to monitor the progression of synaptic activity and network communication. At the single cell level, human neurons exhibited gradually decreasing membrane resistance in parallel with improved excitability by 5 weeks of maturation. Their firing profiles were consistent with those of mature regular firing type of neurons. At the network level we observed the development of abundant fast glutamatergic and depolarizing GABAergic synaptic connections together with synchronized network activity. The identified sequence of differentiation events are consistent and offers a robust framework for developing targeted experiments at varying stages of neuronal maturation. This framework allows for the use of different, age-related methodologies or a singular set of experiments for a culture’s maturation.
The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity

The clinical success of PARP1/2 inhibitors prompts the expansion of their applicability beyond homologous recombination deficiency. Here, we demonstrate that the loss of the accessory subunits of DNA polymerase epsilon, POLE3 and POLE4, sensitizes cells to PARP inhibitors. We show that the sensitivity of POLE4 knockouts is not due to a compromised response to DNA damage or homologous recombination deficiency. Instead, POLE4 deletion generates replication stress with the accumulation of single-stranded DNA gaps upon PARP inhibitor treatment. In POLE4 knockouts, replication stress leads to elevated DNA-PK signaling revealing a role of POLE4 in regulating DNA-PK activation. Moreover, POLE4 knockouts show synergistic sensitivity to the co-inhibition of ATR and PARP. Finally, POLE4 loss enhances the sensitivity of BRCA1-deficient cells to PARP inhibitors and counteracts acquired resistance consecutive to restoration of homologous recombination. Altogether, our findings establish POLE4 as a promising target to improve PARP inhibitor driven therapies and hamper acquired PARP inhibitor resistance.
RoboWorld: Verification of Robotic Systems with Environment in the Loop

A robot affects and is affected by its environment, so that typically its behaviour depends on properties of that environment. For verification, we need to formalise those properties. Modelling the environment is very challenging, if not impossible, but we can capture assumptions. Here, we present RoboWorld, a domain-specific controlled natural language with a process algebraic semantics that can be used to define (a) operational requirements, and (b) environment interactions of a robot. RoboWorld is part of the RoboStar framework for verification of robotic systems. In this article, we define RoboWorld’s syntax and hybrid semantics, and illustrate its use for capturing operational requirements, for automatic test generation, and for proof. We also present a tool that supports the writing of RoboWorld documents. Since RoboWorld is a controlled natural language, it complements the other RoboStar notations in being accessible to roboticists, while at the same time benefitting from a formal semantics to support rigorous verification (via testing and proof).
Reasoning about changes of land covers with fuzzy settings

Change detection of land cover from satellite images is emphasized in China as a result of rapid land cover changes. This paper discusses a method to calculate land cover changes based on fuzzy settings. In this method, land cover is regarded as fuzzy spatial objects rather than crisp objects. The fuzzy land cover is derived based on a fuzzy classification. The degree of change is then calculated using fuzzy reasoning. In order to minimize any errors in image matching, fuzzy polygons are adopted in the reasoning. By incorporating spectral value differences, the errors in image classification can be reduced considerably. The land cover changes from 1989 to 1998 in a part of Sanya City of China are inferred as an example. The results show that this fuzzy method is able to identify the land cover changes more precisely than the crisp method. Furthermore, the transitional land cover changes can be revealed as a by‐product.
Light-sensitive phosphorylation regulates enzyme activity and filament assembly of human IMPDH1 retinal splice variants

Inosine monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in de novo guanosine triphosphate (GTP) synthesis and is controlled by feedback inhibition and allosteric regulation. IMPDH assembles into micron-scale filaments in cells, which desensitizes the enzyme to feedback inhibition by GTP and boosts nucleotide production. The vertebrate retina expresses two tissue-specific splice variants IMPDH1(546) and IMPDH1(595). IMPDH1(546) filaments adopt high and low activity conformations, while IMPDH1(595) filaments maintain high activity. In bovine retinas, residue S477 is preferentially phosphorylated in the dark, but the effects on IMPDH1 activity and regulation are unclear. Here, we generated phosphomimetic mutants to investigate structural and functional consequences of phosphorylation in IMPDH1 variants. The S477D mutation re-sensitized both variants to GTP inhibition, but only blocked assembly of IMPDH1(595) filaments and not IMPDH1(546) filaments. Cryo-EM structures of both variants showed that S477D specifically blocks assembly of the high activity assembly interface, still allowing assembly of low activity IMPDH1(546) filaments. Finally, we discovered that S477D exerts a dominant-negative effect in cells, preventing endogenous IMPDH filament assembly. By modulating the structure and higher-order assembly of IMPDH, phosphorylation at S477 acts as a mechanism for downregulating retinal GTP synthesis in the dark, when nucleotide turnover is decreased. Like IMPDH1, many other metabolic enzymes dynamically assemble filamentous polymers that allosterically regulate activity. Our work suggests that posttranslational modifications may be yet another layer of regulatory control to finely tune activity by modulating filament assembly in response to changing metabolic demands. SIGNIFICANCE STATEMENT Over 20 different metabolic enzymes form micron-scale filaments in cells, suggesting that filament assembly is a conserved mechanism for regulating diverse metabolic pathways. Filament assembly regulates catalytic activity of many of these enzymes, including inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo GTP biosynthesis. The vertebrate retina expresses two IMPDH1 splice variants that are critical for maintaining nucleotide levels required for phototransduction. Here, we show that filament assembly by these variants is itself controlled by phosphorylation at a single residue, adding further complexity to the tight regulation of nucleotide metabolism in the retina. Phosphorylation and other posttranslational modifications are likely to be a general regulatory mechanism controlling filament assembly by enzymes in many different metabolic pathways.
Functional diversity of NLRP3 gain-of-function mutants associated with CAPS autoinflammation

NLRP3-associated autoinflammatory disease (NLRP3-AID or CAPS) is an heterogenous group of monogenic autoinflammations associated with NLRP3 gain-of-function mutations. The poor functional characterization of most NLRP3 variants is a barrier to diagnosis although patients can be efficiently treated with anti-IL-1 approaches. In addition, while NLRP3 inflammasome is controlled by coordinated priming and activation signals, gain-of-functions of NLRP3 variants have been only investigated in response to priming. Here, we functionally characterize 34 NLRP3 variants in vitro by determining their activity in response to induction, priming and/or activation signals, and their sensitivity to inhibitors. We highlight the functional diversity of the gain-of-function mutants and describe four groups based on their profile of signals required for their activation, that correlate partly with the symptoms severities. We identify a new group of NLRP3 mutants responding to the activation signal without priming, with patients often misdiagnosed. Our results identify key NLRP3 residues controlling the inflammasome activity and sensitivity to inhibitors. The comparison of four inhibitors on the 34 variants identifies inhibitory mechanisms with broader efficiency for future drug design. Altogether, our results provide new insights on NLRP3 activation and an explanatory mechanism for NLRP3-AID heterogeneity, and original tools for NLRP3-AID diagnosis and anti-inflammatory disease drug development. eTOC Summary Functional characterization of 34 CAPS-associated NLRP3 variants identifies polymorphisms versus gain-of-function pathogenic mutants, and highlights diversities in the signals controlling their activation and in their sensitivity to inhibitors. This study provides tools for CAPS diagnosis and anti-inflammation drug development and insights on NLRP3 control mechanisms.
Subnet Communicability: Diffusive Communication Across the Brain Through a Backbone Subnetwork

One of the fundamental challenges in modern neuroscience is understanding the interplay between the brain’s functional activity and its underlying structural pathways. To address this question, we propose a novel communication pattern called subnet communicability, which models diffusive communication between pairs of regions through a small, intermediary subnetwork of brain regions as opposed to spreading messages through the entire network. We demonstrate that subnet communicability strengthens coupling between the structural and functional connectomes better than previous models, including communicability. Over two large datasets, we show that the optimal subnetwork is consistent across the population. Subnet communicability provides new insights into structure-function coupling in the brain and offers a balance between redundancy in message passing and economy of brain wiring.
Integrated genomics provides insights for the evolution of the polyphosphate accumulation trait of Ca. Accumulibacter

Candidatus Accumulibacter plays a major role in enhanced biological phosphorus removal (EBPR), but the key genomic elements in metagenome assembled genomes enabling their phosphorus cycling ability remain unclear. Pangenome analyses were performed to systematically compare the genomic makeup of Ca. Accumulibacter and non-Ca. Accumulibacter members within the Rhodocyclaceae family. Metatranscriptomic analyses of an enrichment culture of Ca. Accumulibacter clade IIC strain SCUT-2 were performed to investigate gene transcription characteristics in a typical anaerobic-aerobic cycle. Two hundred ninety-eight core genes were shown to be obtained by Ca. Accumulibacter at their least common ancestor. One hundred twenty-four of them were acquired via horizontal gene transfer (HGT) based on best-match analysis against the NCBI database. Fourty-four laterally derived genes were actively transcribed in a typical EBPR cycle, including the polyphosphate kinase 2 (PPK2) gene. Genes in the phosphate regulon (Pho) were poorly transcribed. Via a systematical analysis of the occurrences of these genes in closely related Dechloromonas-polyphosphate accumulating organisms (PAOs) and Propionivibrio-non-PAOs, a Pho dysregulation hypothesis is proposed to explain the mechanism of EBPR. It states that the PhoU acquired by HGT fails in regulating the high-affinity phosphate transport (Pst) system. To avoid phosphate poisoning, the laterally acquired PPK2 is employed to condense excess phosphate into polyphosphate. Alternatively, genes encoding PhoU and PPK2 are obtained from different donor bacteria, leading to unmatched phosphate concentration thresholds for their activation/inactivation. PPK2 tends to reduce the intracellular phosphate to concentration levels perceived by PhoU as low-phosphate states. PhoU is not activated to turn off the Pst system, resulting in continuous phosphate uptake. In conclusion, based on integrated genomic analyses, the HGT of phoU and ppk2 and the resultant Pho dysregulation may have triggered the development and evolution of the P cycling trait in Ca. Accumulibacter.
The effect of sediment type on the relationship between reflectance and suspended sediment concentration

Abstract The use of remotely-sensed optical data to estimate the suspended sediment concentration (SSC) of water is dependent upon the correlation between SSC and reflectance. The strength of this relationship was hypothesized to vary with sediment type, as it is known that sediments, when dry, differ in their particle size distributions, colour and therefore reflectance properties. To test this, the reflectance of pure water with four concentrations of white clay and red silt were measured in the laboratory using a spectroradiometer. The correlation between SSC and reflectance varied with wavelength and sediment type. For white clay the correlations were very high (r≃0·98) in visible and near-infrared wavelengths but for the red silt it was lower (r≃0·8) in blue wavelengths increasing to much higher levels (r≃0·98) in blue/green and longer wavelengths. It was concluded that sediment type can affect the strength of the correlation between SSC and reflectance and that this will be most noticeable at shorte.
Prevalence of HIV, Sexually Transmitted Disease and Tuberculosis amongst New Prisoners in a District Prison, Malawi

Infectious diseases, particularly tuberculosis (TB) and the human immunodeficiency virus infection (HIV) are reported to be highly prevalent amongst prisoners in many countries of the world1. Sub-saharan Africa has the highest rates ofTB, HIV and sexually transmitted diseases (STDs) in the world2•3. However, there is a scarcity of information about the prevalence of these infections amongst prisoners. A study in Zomba Central Prison in Malawi" found a high prevalence of pulmonary TB (PTB) and HIV amongst prison inmates. This finding leads to the implementation of a system of screening patients for PTB in eight of the country's prisons in which there are medical staff. Unfortunately, there are another 14 district prisons in the country which do not have medical staff. Although new prisoners to such prisons are supposed to be assessed by staff from the nearest district hospital, in practice this rarely happens because of problems such as staff shortages and transport difficulties. We decided to perform a clinical assessment of new prisoners who were admitted to a district prison in Malawi in which there was no medical staff, with a particular focus on HIV, STDs and TB. Ntcheu district is in the central region of Malawi, with a population of 500000. There is one district hospital and one prison, situated in the township itself. There are no medical personnel attached to the prison, and prisoners are taken to hospital when sick. The total number of prison inmates varies from 60-120. There are five cells for male prisoners and one for female prisoners. These cells are small and poorly ventilated, and at maximum capacity, there is on average 0.6 m2 of cell space for each prisoner. For the purpose of this study, a clinical officer from the district hospital visited the prison once a week and screened all new prisoners. A history and physical examination were performed, which included an examination for STDs according to World Health Organization Syndromic Management Guidelines. In all prisoners, whether they were coughing or not, an attempt was made to collect sputum specimens for detection of alcohol-acid fast bacilli (AAFB). Sputum smears were prepared and examined for AAFB using light microscopy and the Ziehl-Neelsen stain in the hospital laboratory. Prisoners were counselled for HIV-testing, and in those accepting the test post-test counselling was carried out according to the guidelines of the National AIDS Control Programme. Blood was examined for HIV using a particle agglutination test (Serodia-HIV, Fujirebio, Tokyo). Clinical illness, STDs and PTB were treated according to the country's established guidelines. Between June and November 1997, 275 new prisoners were admitted to Ntcheu Prison, 272 men and three women, whose mean age was 28 years. Of these 21 prisoners were discharged before they were examined, leaving 254 on whom an examination was carried out. HIV status: 58 prisoners (23%) accepted HIV testing and 47 were actually screened. Of 47 prisoners tested, 15 (32%) were HIV-positive.
Four new pollen sections tracing the Holocene vegetational development of the southern part of the West Siberan Lowland

In the southeast of Western Siberia within the zone of birch and pine forests in the Ob'-Tom' interfluve area, four new pollen diagrams from sites in different landforms (interfluve, terraces, floodplain, and ancient drainageways) with sandy and clay soils were correlated with two published pollen diagrams. Two main types of pollen stratigraphy are characteristic for areas with clay and sandy soils, reflecting different vegetational developments during the Holocene that were controlled by changes in climate and soil properties. Open birch forest-steppe with Artemisia and Chenopodiaceae was widespread in the Ob'-Tom' interfluve during the early Holocene, whereas the young floodplains had flooded meadows and willow scrub. The principal vegetation change from open steppe and forest-steppe to dense forest took place about 7000 yr BP, after which forest vegetation has prevailed. On sandy soils the dominant tree species was Pinus sylvestris throughout, but on clay Pinus sibirica and Abies sibirica together with Betula pendula had more important roles, alternating periodically with Pinus sylvestris. Expansion of Pinus sibirica and Abies sibirica in this area started about 4500-4000 yr BP, but in some places they declined markedly during recent centuries due to human influence. Based on the vegetational development, the climate in the southeast of Western Siberia changed from colddry to warm-dry (9500 yr BP) then to warm-wet (7000 yr BP), and finally to cool-wet (4000 yr BP).
OSHI-Open Source Hybrid IP / SDN networking ( and its emulation on Mininet and on distributed

DISCLAIMER This work has been partly funded by the EU in the context of GN3plus project (http://www.geant.net/), but it does not necessarily represent the official position of the project itself and of its partners. Authors are solely responsible for the views, results and conclusions contained in this work. COPYRIGHT "Copyright and all rights therein are retained by authors. This work may not be modified or reposted without the explicit permission of the copyright holder"
PREPLANTING SOIL MOISTURE USING PASSIVE MICROWAVE SENSORS

ABSTRACT: Accurate assessment of preplanting soil moisture conditions is necessary for good agricultural management, and can have a significant influence on crop yield in the Texas Panhandle region. The Texas High Plains Underground Water Conservation District invests considerable time and money in developing a soil moisture deficit map each year in the hopes of achieving optimal use of irrigation water. Microwave sensors are responsive to surface soil moisture and, if used in this application, can provide timely and detailed information on root zone soil moisture. For this reason, an experiment was conducted in 1984 to evaluate the potential of aircraft-mounted passive microwave sensors. Microwave radiometer data were collected over a 2700 km2 area near Lubbock, Texas, with a processed resolution of 0.32 km2. These data were ground registered and converted to estimates of soil moisture using an appropriate model and land cover and soil texture information. Analyses indicate that the system provides an efficient means for mapping variations in soil moisture over large areas.
General hierarchical approach in absolute phase measurement

Starting from a description of the absolute phase problem in fringe processing and a discussion of existing solutions a general approach for robust absolute phase measurement in optical metrology is presented. Using this method the continous phase field can be reconstructed with high accuracy by a stepwise or so called hierarchical approach without any interaction necessary in conventional phase unwrapping if technical objects have to be investigated. The determination of the sequence of synthetic wavelengths is strongly oriented on the phase measuring accuracy and the known limits of the absolute phase. Keywords: optical metrology, shape measurement, displacement measurement, fringe processing, absolute phase measurement
Equity Integration in Japan: An Application of a New Method

This paper develops a simple new methodology to test for asset integration and applies it to the Japanese stock market as represented by the Tokyo Stock Exchange (TSE). The technique is tightly based on a general intertemporal asset-pricing model, and relies on estimating and comparing expected risk-free rates across assets. Expected risk-free rates are allowed to vary freely over time, constrained only by the fact that they are equal across (risk-adjusted) assets. Assets are allowed to have general risk characteristics, and are constrained only by a factor model of covariances over short time periods. The technique is undemanding in terms of both data and estimation. I find that expected risk-free rates vary dramatically over time, unlike short-term interest rates. Further, the TSE does not always seem to be well integrated in the sense that different portfolios of stocks are priced with different implicit risk-free rates.
TNF-I AND ITS ASSOCIATION WITH NITRIC OXIDE SYNTHASE GENE IN PREECLAMPSIA

Pathophysiological processes in preeclampsia (PE) are influenced by genetic factors. To better characterize the host genetic factors determining the susceptibility to PE, we evaluated the influence of two polymorphisms in the NOS2A gene on the risk of developing PE and correlated with TNF& α. The polymorphisms were studied by DNA sequencing and the levels of TNF& α were measured by high sensitivity enzyme&linked immunosorbant assay. The study subjects were 30 pre&eclamptic women compared by age matched 30 healthy pregnant women. Kruskal&Wallis non&parametric analyses of variance followed by Mann&Whitney U&tes t were used for statistical analysis. Both (G300A Exon8 and G274TExon16) single nucleotide polymorphism (SNP) showed statistically significant association with preeclampsia (p< 0.05). The levels of TNF& α in pre&eclamptic subject were increased significantly when compared with the healthy controls (P < 0.001). Higher TNF& α level was observed in TT genotypes of G274T Exon16 in comparison to GG or GT genotypes in preeclamptic patients.These results indicate the relationship between increased TNF& α levels and NOS2A polymorphism leading to its altered expression in preeclamptic patients.