Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional and Morpho-Physiological Responses of Marchantia polymorpha upon Phosphate Starvation

Phosphate (Pi) is a pivotal nutrient that constraints plant development and productivity in natural ecosystems. Land colonization by plants, more than 470 million years ago, evolved adaptive mechanisms to conquer Pi-scarce environments. However, little is known about the molecular basis underlying such adaptations at early branches of plant phylogeny. To shed light on how early divergent plants respond to Pi limitation, we analyzed the morpho-physiological and transcriptional dynamics of Marchantia polymorpha upon Pi starvation. Our phylogenomic analysis highlights some gene networks present since the Chlorophytes and others established in the Streptophytes (eg. PHR1-SPX1 and STOP1-ALMT1, respectively). At the morpho-physiological level, the response is characterized by the induction of phosphatase activity, media acidification, accumulation of auronidins, reduction of internal Pi concentration and developmental modifications of rhizoids. The transcriptional response involves the induction of MpPHR1, Pi transporters, lipid turnover enzymes and MpMYB14, an essential transcription factor for auronidins biosynthesis. MpSTOP2 up-regulation correlates with expression changes in genes related to organic acid biosynthesis and transport, suggesting preference for citrate exudation. Analysis of MpPHR1 binding sequences (P1BS) shows enrichment of this cis regulatory element in differentially expressed genes. Our study unravels the strategies, at diverse levels of organization, exerted by M. polymorpha to cope with low Pi availability. Significance Statement This study unravels the transcriptional and morphophysiological mechanisms executed by the non-vascular, and rootless, plant Marchantia polymorpha upon phosphate starvation conditions. The findings in this study shed light on the mechanisms that early land plants may have developed for the conquest of substrates poor in available phosphate, some of which are still conserved by current-day plants. Moreover, our results open several working hypotheses and novel perspectives for the study of Pi-starvation responses along plant evolution.
Orientation of Directional Deep Brain Stimulation Leads on CT: Resolving the Ambiguity

While directional deep brain stimulation (DBS) shows promising clinical effects by providing a new degree of freedom in programming, precise knowledge of the lead position and orientation is necessary to mitigate the resulting increased complexity. Two methods for orientation assessment based on postoperative CT imaging have become available, but neither of them is currently able to resolve the respective 180° artifact symmetry. Both rely on information about the intended orientation and assume that a deviation of more than ± 90° is very unlikely. Our aim was to develop an enhanced algorithm capable of detecting asymmetries in the CT data and to thus eliminate the need for user interaction. Two different approaches are presented: one based on the lead marker’s center of mass (COM) and one based on asymmetric sampling of the marker’s intensity profile (ASM). Both were tested on a total of 98 scans of 2 lead phantoms, resulting in 165 measurements with a large variety of lead implantation and orientation angles. The 180° ambiguity was correctly resolved in 99.4% of cases by COM and in 96.4% of cases by ASM. These results demonstrate the substantial and currently unused asymmetry in CT and the potential for a truly automated workflow.
Demystifying Deep Learning: Developing a Learning App for Beginners to Gain Practical Experience

Deep learning has revolutionized machine learning, enhancing our ability to solve complex computational problems. From image classification to speech recognition, the technology can be beneficial in a broad range of scenarios. However, the barrier to entry is quite high, especially when programming skills are missing. In this paper, we present the development of a learning application for beginners that is easy to use, yet powerful enough to solve practical deep learning problems. We followed the human-centered design approach and conducted a technical evaluation to identify solvable classification problems. In the future, we plan to conduct a user study to evaluate our learning application online.
On Combining IR Methods to Improve Bug localization

Information Retrieval (IR) methods have been recently employed to provide automatic support for bug localization tasks. However, for an IR-based bug localization tool to be useful, it has to achieve adequate retrieval accuracy. Lower precision and recall can leave developers with large amounts of incorrect information to wade through. To address this issue, in this paper, we systematically investigate the impact of combining various IR methods on the retrieval accuracy of bug localization engines. The main assumption is that different IR methods, targeting different dimensions of similarity between artifacts, can be used to enhance the confidence in each others' results. Five benchmark systems from different application domains are used to conduct our analysis. The results show that a) near-optimal global configurations can be determined for different combinations of IR methods, b) optimized IR-hybrids can significantly outperform individual methods as well as other unoptimized methods, and c) hybrid methods achieve their best performance when utilizing information-theoretic IR methods. Our findings can be used to enhance the practicality of IR-based bug localization tools and minimize the cognitive overload developers often face when locating bugs.
Transcriptome analysis of EPO and GFP HEK293 Cell-lines Reveal Shifts in Energy and ER Capacity Support Improved Erythropoietin Production in HEK293F Cells

Higher eukaryotic cell lines like HEK293 are the preferred hosts for production of therapeutic proteins requiring human post translational processing. However, recombinant protein production can result in severe stress on the cellular machinery, resulting in limited titre and product quality. To investigate the cellular and metabolic characteristics associated with these limitations, we compared erythropoietin (secretory) and GFP (non-secretory) protein producer HEK293 cell-lines using transcriptomics analysis. Despite the high demand for ATP in all protein producer clones, a significantly higher capacity for ATP production was observed with erythropoietin producers as evidenced by the enrichment of upregulated genes in the oxidative phosphorylation pathway. In addition, ribosomal genes exhibited specific patterns of expression depending on the recombinant protein and the production rate. In a clone displaying a dramatically increased erythropoietin secretion, we detected higher ER stress, including upregulation of the ATF6B gene. Our results are significant in recognizing key pathways for recombinant protein production and identifying potential target genes for further development of secretory power in mammalian cell factories. In Brief Although the protein secretion process has been widely studied, the complexity of it leaves many questions with regards to defining bottlenecks for successful protein secretion to be answered. By investigating the transcriptomic profiles of different HEK293 clones with varying translational rates producing either the secreted protein erythropoietin or the intracellular GFP, we reveal that high ATP production and improved capacity of specific post-translational pathways are key factors associated with boosting erythropoietin production. Highlights Transcriptomics analysis of a panel of HEK293 stable cell lines expressing GFP or erythropoietin (EPO) at varying translational rates Expression of mitochondrial ribosomal genes is positively correlated with EPO secretion Expression of different cytosolic ribosomal genes are correlated with productivity in a recombinant-protein specific manner High EPO producing clones have significant upregulation of ATF6B, potentially enabling a beneficial ER stress response to cope with high protein secretion Graphical Abstract
Cooperative NOMA system with incremental relaying and energy harvesting: Performance analysis and optimization

This article investigates the outage performance of incremental relaying based energy harvesting non‐orthogonal multiple access (IR‐EH‐NOMA) system. Firstly, we describe the IR‐EH‐NOMA protocol considering downlink user assisted relaying and power splitting (PS) based EH strategy. We derive analytical expressions for the outage probabilities experienced by the downlink users and the system outage probability of IR‐EH‐NOMA network, in the presence of imperfect successive interference cancellation (I‐SIC). For comparison, we derive the corresponding outage expressions for the conventional cooperative relaying based NOMA network with EH (CR‐EH‐NOMA network) as well. We provide extensive numerical and Monte‐Carlo simulation results to establish the supremacy of IR‐EH‐NOMA system over CR‐EH‐NOMA system in terms of the outage performance. We separately derive analytical expressions for (i) the optimal power allocation (OPA) factor at the source and (ii) the optimal power splitting (OPS) factor at the relay that minimizes the asymptotic system outage probability of the considered networks. With the help of numerical and simulation investigations, we establish that the system outage of the considered networks improve significantly when OPA and OPS factors are selected according to the criterion described in the article. The analytical results are validated by extensive simulation studies.
The Role of Pedagogical Practices in Novice Teachers' Work

Achieving educational goals is based on the skills and competence of teachers; therefore, professional development of teachers is important to policy and decision-makers. Worldwide, the percentage of teachers who leave the profession within their first years of teaching is high therefore, professional support is essential to ease on their integration. Previous research indicates a positive and significant correlation between teachers' self-efficacy and their attitudes toward the teaching profession. Our study included three hypotheses: 1) teachers' pedagogical applications serve as mediators for the relationship between teachers' selfefficacy and their attitudes toward the profession; 2) participating in a professional development school (PDS) training program interacts with teachers' self-efficacy in predicting their attitudes toward the profession; and, 3) participation in a PDS training program will positively affect the two variables. A close and open-ended questionnaire was replied by 300 novice teachers, some of whom participated in the PDS program and others who did not. Findings indicate that the relationship between teachers' sense of self-efficacy and their attitudes towards the teaching profession was partially mediated by: applying constructivist pedagogical practices; matching to differences between learners; collaboration between fellow teachers; accountability; planning and teaching management; and academy-community relationships. Participation in a PDS program was not found as a moderator variable for this relationship, but novice teachers who participated in this program had a significant higher sense of self-efficacy and more positive attitudes towards the teaching profession. Findings are important for designing novice teacher training programs with an emphasis on the implementation of specific pedagogical practices.
An Empirical Study on Critical Blocking Bugs

Blocking bugs are a severe type of bugs that prevent other bugs from being fixed. As software becomes increasingly complex and large, blocking bugs occur in many large-scale software, especially in software ecosystems. Blocking bugs may have a high negative impact on software development and maintenance. Usually, blocking bugs preventing more bugs should be more concerned. In this paper, we focus on a special type of blocking bugs that block at least two bugs, which we call Critical Blocking Bugs (CBBs). We study CBBs from the following five aspects: the importance, the repair time, the scale of repair, the experience of developers who repair CBBs, and the circumstance why CBBs block multiple bugs. We build a dataset containing five open source projects and classify bugs into three types (i.e., critical blocking bugs, normal blocking bugs and other bugs, which block at least two, just one and zero bugs, respectively) to compare the differences between CBBs and other types of bugs. The experimental results show that CBBs are more important with longer repair time and larger repair scale, and CBBs are concentrated on parts of components of the project. These results highlight that CBBs are different from other types of bugs in many aspects, and we should pay more attention to such bugs in the future software maintenance process.
Multipath TCP security over different attacks

Due to the increasing demand for bandwidth and availability of multi‐homed devices, the Multipath TCP (MPTCP) is an emerging protocol that uses multiple paths simultaneously to transfer the data, seamlessly utilizing their bandwidth. The security is an important issue in a system especially the communication network system. Since there are multiple paths in MPTCP, it has many doors open to an adversary especially at the time of connection initiation. These attacks include the man‐in‐the‐middle attack (MM), denial‐of‐service (DOS) attack, and SYN flooding attack. This article proposes a new opportunistic security protocol, named as secure connection multipath TCP (SCMTCP), that uses the elliptic curve cryptography to generate the secret key. It also uses a third‐party certificate authority to ensure the authenticity of public keys exchanged between the communicating parties. The SCMTCP generates a session key at the time of initial handshake (with MP_CAPABLE option) and protects the MPTCP from the man‐in‐the‐middle attack. It generates a unique authentication key for each new subflow within the host using the session key to authenticate them and protects the MPTCP from DoS and SYN flooding attacks. This article analyzes the security complexity of the SCMTCP using the random oracle model and shows that it is not possible for an attacker to get any security key and breaks the MPTCP security.
Properties of the axial current of retinal ganglion cells at spike initiation

The action potential of most vertebrate neurons initiates in the axon initial segment (AIS), and is then transmitted to the soma where it is regenerated by somatodendritic sodium channels. For successful transmission, the AIS must produce a strong axial current, so as to depolarize the soma to the threshold for somatic regeneration. Theoretically, this axial current depends on AIS geometry and Na+ conductance density. We measured the axial current of mouse RGCs using whole-cell recordings with post-hoc AIS labeling. We found that this current is large, implying high Na+ conductance density, and carries a charge that co-varies with capacitance so as to depolarize the soma by ∼30 mV. Additionally, we observed that the axial current attenuates strongly with depolarization, consistent with sodium channel inactivation, but temporally broadens so as to preserve the transmitted charge. Thus, the AIS appears to be organized so as to reliably backpropagate the axonal action potential.
A clock in mouse cones contributes to the retinal oscillator network and to synchronization of the circadian system

Multiple circadian clocks dynamically regulate mammalian physiology. In retina, rhythmic gene expression serves to align vision and tissue homeostasis with daily light changes. Photic input is relayed to the suprachiasmatic nucleus to entrain the master clock, which matches behaviour to environmental changes. Circadian organization of the mouse retina involves coordinated, layer-specific oscillators, but so far little is known about the cone photoreceptor clock and its role in the circadian system. Using the cone-only Nrl-/- mouse model we show that cones contain a functional self-sustained molecular clockwork. By bioluminescence-combined imaging we also show that cones provide substantial input to the retinal clock network. Furthermore, we found that light entrainment and negative masking in cone-only mice are subtly altered and that constant light displayed profound effects on their central clock. Thus, our study demonstrates the contribution of cones to retinal circadian organisation and their role in finely tuning behaviour to environmental conditions.
Predictive regulatory and metabolic network models for systems analysis of Clostridioides difficile

Though Clostridioides difficile is among the most studied anaerobes, we know little about the systems level interplay of metabolism and regulation that underlies its ability to negotiate complex immune and commensal interactions while colonizing the human gut. We have compiled publicly available resources, generated through decades of work by the research community, into two models and a portal to support comprehensive systems analysis of C. difficile. First, by compiling a compendium of 148 transcriptomes from 11 studies we have generated an Environment and Gene Regulatory Influence Network (EGRIN) model that organizes 90% of all genes in the C. difficile genome into 297 high quality modules based on evidence for their conditional co-regulation by at least 120 transcription factors. EGRIN predictions, validated with independently-generated datasets, have recapitulated previously characterized C. difficile regulons of key transcriptional regulators, refined and extended membership of genes within regulons, and implicated new genes for sporulation, carbohydrate transport and metabolism. Findings further predict pathogen behaviors in in vivo colonization, and interactions with beneficial and detrimental commensals. Second, by advancing a constraints-based metabolic model, we have discovered that 15 amino acids, diverse carbohydrates, and 24 genes across glyoxylate, Wood-Ljungdahl, nucleotide, amino acid, and carbohydrate metabolism are essential to support growth of C. difficile within an intestinal environment. Models and supporting resources are accessible through an interactive web portal (http://networks.systemsbiology.net/cdiff-portal/) to support collaborative systems analyses of C. difficile.
Transcriptional alterations in opioid use disorder reveal an interplay between neuroinflammation and synaptic remodeling

Prevalence rates of opioid use disorder (OUD) have increased dramatically, accompanied by a surge of overdose deaths. While opioid dependence has been extensively studied in preclinical models, we still have a very limited understanding of the biological changes that occur in the brains of people who chronically use opioids and who are diagnosed with OUD. To address this, we conducted the largest transcriptomics study to date using postmortem brains from subjects with OUD. We focused on the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc), two regions heavily implicated in OUD. We discovered a high degree of overlap in transcripts between DLPFC and NAc in OUD, primarily associated with neuroinflammation. Moreover, additional transcripts were enriched for factors that control pro-inflammatory cytokine-mediated signaling and remodeling of the extracellular matrix (ECM). Our results also implicate a role for microglia as a critical driver for opioid-induced neuroplasticity. Overall, our findings reveal new connections between the brain’s immune system and opioid dependence in the human brain.
Optimization of Ultrasound-Assisted Extraction of Total Flavonoids Content from the White Flowering Variety of Melastoma Malabathricum

Melastoma malabathricum or Senduduk Putih is one of the herbs listed under National Key Economic Area (NKEA) of Malaysia. It has the potential to be used as remedies that is rich in natural flavonoids. One of the innovations for extraction in modern technology is Ultrasound-Assisted Extraction (UAE) that showed several advantages. Therefore, this study aimed to explore using UAE to extract the total flavonoids in M. malabathricum. After that, UAE is optimized coupled with a stirrer for total flavonoid extraction. Five operating parameters: ethanol concentration, plant material to solvent ratio, extraction temperature, extraction time and ultrasound power were investigated by one-factor-at-a-time (OFAT) method to choose the most important parameters. After that, the response surface methodology coupled with face-centered central composite design (FCCD) was employed to study the interaction of the three keys parameters. The optimized conditions to extract total flavonoids content by UAE with constant mixing speed (300 ± 6 rpm) were at a ratio of 1g of plant material: 30 mL of 100% (v/v) ethanol, extraction temperature at 70oC, 19 min of extraction time and 280 W of ultrasound power. The experimental yields of total flavonoids content were 64.94 mg/g, which is well matched with the predicted value of 63.75 mg/g.
Compartmentalization of mRNAs in the giant, unicellular green algae Acetabularia acetabulum

Acetabularia acetabulum is a single-celled green alga previously used as a model species for studying the role of the nucleus in cell development and morphogenesis. The highly elongated cell, which stretches several centimeters, harbors a single nucleus located in the basal end. Although A. acetabulum historically has been an important model in cell biology, almost nothing is known about its gene content, or how gene products are distributed in the cell. To study the composition and distribution of mRNAs in A. acetabulum, we have used quantitative RNA-seq to sequence the mRNA content of four sections of adult A. acetabulum cells. We found that although mRNAs are present throughout the cell, there are large pools of distinct mRNAs localized to the different subcellular sections. Conversely, we also find that gene transcripts related to intracellular transport are evenly distributed throughout the cell. This distribution hints at post-transcriptional regulation and selective transport of mRNAs as mechanisms to achieve mRNA localization in A. acetabulum.
Nematode assemblages of the northern Gulf of Mexico continental shelf

Abstract. — This study examined free-living marine nematode assemblages of the northern Gulf of Mexico (GOM) continental shelf and their relationship to sediment characteristics. Sediment cores were collected in Fall 2012 and analyzed for trace metals, organic carbon, granulometry, and nematode genera. This study reports 100 genera of nematodes from 26 families, including 18 genera previously unreported in the GOM. A listing of the nematode diversity provides a bioinventory of nematodes on the GOM shelf. Cluster analysis, non-metric multidimensional scaling (nMDS) and principal component analysis revealed a distinction between eastern and western samples based on sediment characteristics as well as nematode assemblages. Spearman correlations revealed a significant correlation between sediment characteristics and nMDS coordinates, also suggesting that nematode assemblages have an east/west distinction that is reflective of their habitat. This study adds information on the biodiversity of marine nematodes, an abundant and diverse taxon from an area that is subject to anthropogenic disturbance.