Miracle-dz/UniFAR-FTUs huggingface dataset:
CD38 produces nicotinic acid adenosine dinucleotide phosphate in the lysosome

Nicotinic acid adenosine dinucleotide phosphate (NAADP) is a Ca2+-mobilizing second messenger that regulates a wide range of biological activities. However, the mechanism of its biogenesis remains controversial. CD38 is the only enzyme known to catalyze NAADP synthesis from NADP and nicotinic acid. CD38-mediated catalysis requires an acidic pH, suggesting that NAADP may be produced in acidic endolysosomes, but this hypothesis is untested. In this study, using human cell lines, we specifically directed CD38 to the endolysosomal system and assessed cellular NAADP production. First, we found that nanobodies targeting various epitopes on the C-terminal domain of CD38 could bind to cell surface–localized CD38 and induce its endocytosis. We also found that CD38 internalization occurred via a clathrin-dependent pathway, delivered CD38 to the endolysosome, and elevated intracellular NAADP levels. We also created a CD38 variant for lysosome-specific expression, which not only withstood the degradative environment in the lysosome, but was also much more active than WT CD38 in elevating cellular NAADP levels. Supplementing CD38-expressing cells with nicotinic acid substantially increased cellular NAADP levels. These results demonstrate that endolysosomal CD38 can produce NAADP in human cells. They further suggest that CD38's compartmentalization to the lysosome may allow for its regulation via substrate access, rather than enzyme activation, thereby providing a reliable mechanism for regulating cellular NAADP production.
Self-Growth of Basic Behaviors in an Action Selection Based Agent

We investigate on designing agents facing multiple objectives simultaneously, that creates difficult situations, even if each objective is of low complexity. The present paper builds on an existing action selection process based on basic behaviors (resulting in a modular architecture) and proposes an algorithm for automatically selecting and learning the required basic behaviors through an incremental Reinforcement Learning approach. This leads to a very autonomous architecture, as the hand-coding is here reduced to its minimum.
APIEvolutionMiner: Keeping API evolution under control

During software evolution, source code is constantly refactored. In real-world migrations, many methods in the newer version are not present in the old version (e.g.,60% of the methods in Eclipse 2.0 were not in version 1.0). This requires changes to be consistently applied to reflect the new API and avoid further maintenance problems. In this paper, we propose a tool to extract rules by monitoring API changes applied in source code during system evolution. In this process, changes are mined at revision level in code history. Our tool focuses on mining invocation changes to keep track of how they are evolving. We also provide three case studies in order to evaluate the tool.
Robust Visual Localization Across Seasons

Localization is an integral part of reliable robot navigation, and long-term autonomy requires robustness against perceptional changes in the environment during localization. In the context of vision-based localization, such changes can be caused by illumination variations, occlusion, structural development, different weather conditions, and seasons. In this paper, we present a novel approach for localizing a robot over longer periods of time using only monocular image data. We propose a novel data association approach for matching streams of incoming images to an image sequence stored in a database. Our method exploits network flows to leverage sequential information to improve the localization performance and to maintain several possible trajectories hypotheses in parallel. To compare images, we consider a semidense image description based on histogram of oriented gradients features as well as global descriptors from deep convolutional neural networks trained on ImageNet for robust localization. We perform extensive evaluations on a variety of datasets and show that our approach outperforms existing state-of-the-art approaches.
Effects of Higher Order and Long-Range Synchronizations for Classification and Computing in Oscillator-Based Spiking Neural Networks

Development of artificial oscillator-based spiking neural networks (SNN), which are able to solve effectively various cybernetics problems including image recognition and adaptive control, is a key line of research. We have thoroughly explored the scheme of two thermally coupled $VO_2$ oscillators and found its effect of high order synchronization (HOS), which may be used to increase SNN classification capacity $N_s$. Phase-locking estimation method has been developed to determine values of subharmonic ratio SHR and synchronization effectiveness {\eta}. The experimental scheme has $N_s=12$ and SHR distributions are shaped as Arnold's tongues. In a model $N_s$ may reach maximum of $N_s>150$ at certain levels of coupling strength and noise. We demonstrate the long-range synchronization effect in a one-dimensional chain of oscillators and the phenomenon of synchronization transfer even at low values of {\eta} for intermediate links. The paper demonstrates realization of analogue operation of "multiplication", binary logic, and possibility of development of the interface between SNN and computer. The described effects increasing classification capacity of oscillator schemes and calculation principles based on the universal physical effect - HOS may be applied for any spiking type oscillators with any coupling type therefore enhancing practical value of the presented results to expand SNN capabilities.
Histone deacetylase 2 is involved in µ-opioid receptor suppression in the spinal dorsal horn in a rat model of chronic pancreatitis pain

Chronic pain occurs in ~85–90% of chronic pancreatitis (CP) patients. However, as the pathogenesis of CP pain remains to be fully understood, the current therapies for CP pain remain inadequate. Emerging evidence has suggested that the epigenetic modulations of genes are involved in chronic pain. In the present study, intrapancreatic trinitrobenzene sulfonic acid infusions were used to establish a CP model in rats. Mechanical allodynia was measured with von Frey filaments. Immunofluorescent staining analysis was used to observe the expression changes of histone deacetylase 2 (HDAC2) and µ-opioid receptor (MOR), and intrathecal administration of the selective HDAC2 inhibitor AR-42 was used to assess the underlying mechanisms. The expression levels of c-Jun N-terminal kinase (JNK) in the thoracic spinal cord were detected by western blotting, and the mRNA expression levels of interleukin (IL)1-β, IL-6 and tumor necrosis factor (TNF)-α were detected by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that HDAC2 expression was upregulated during the course of CP induction, while MOR activity in the thoracic spinal dorsal horn was significantly suppressed. Intrathecal infusion of AR-42 significantly attenuated CP-induced mechanical allodynia, with rescued MOR activity. Additionally, HDAC2 facilitated the release of inflammatory cytokines, including IL-1β, IL-6 and TNF-α. These results suggested that the underlying mechanisms of HDAC2 regulating MOR activity under CP induction may occur via promoting the release of inflammatory cytokines, thus activating the JNK signaling pathway. The present study suggested that the epigenetic-regulated disturbance of MOR is dependent on the endogenous analgesia system in CP, which may a provide novel therapeutic strategy for treating pain in CP.
The Complexity of Posttranscriptional Small RNA Regulatory Networks Revealed by In Silico Analysis of Gossypium arboreum L. Leaf, Flower and Boll Small Regulatory RNAs

MicroRNAs (miRNAs) and secondary small interfering RNAs (principally phased siRNAs or trans-acting siRNAs) are two distinct subfamilies of small RNAs (sRNAs) that are emerging as key regulators of posttranscriptional gene expression in plants. Both miRNAs and secondary-siRNAs (sec-siRNAs) are processed from longer RNA precursors by DICER-LIKE proteins (DCLs). Gossypium arboreum L. , also known as tree cotton or Asian cotton, is a diploid, possibly ancestral relative of tetraploid Gossypium hirsutum L. , the predominant type of commercially grown cotton worldwide known as upland cotton. To understand the biological significance of these gene regulators in G. arboreum, a bioinformatics analysis was performed on G. arboreum small RNAs produced from G. arboreum leaf, flower, and boll tissues. Consequently, 263 miRNAs derived from 353 precursors, including 155 conserved miRNAs (cs-miRNAs) and 108 novel lineage-specific miRNAs (ls-miRNAs). Along with miRNAs, 2,033 miRNA variants (isomiRNAs) were identified as well. Those isomiRNAs with variation at the 3’-miRNA end were expressed at the highest levels, compared to other types of variants. In addition, 755 pha-siRNAs derived 319 pha-siRNA gene transcripts (PGTs) were identified, and the potential pha-siRNA initiators were predicted. Also, 2,251 non-phased siRNAs were found as well, of which 1,088 appeared to be produced by so-called cis- or trans-cleavage of the PGTs observed at positions differing from pha-siRNAs. Of those sRNAs, 148 miRNAs/isomiRNAs and 274 phased/non-phased siRNAs were differentially expressed in one or more pairs of tissues examined. Target analysis revealed that target genes for both miRNAs and pha-siRNAs are involved a broad range of metabolic and enzymatic activities. We demonstrate that secondary siRNA production could result from initial cleavage of precursors by both miRNAs or isomiRNAs, and that subsequently produced phased and unphased siRNAs could result that also serve as triggers of a second round of both cis- and trans-cleavage of additional siRNAs, leading to the formation of complex sRNA regulatory networks mediating posttranscriptional gene silencing. Results from this study extended our knowledge on G. arboreum sRNAs and their biological importance, which would facilitate future studies on regulatory mechanism of tissue development in cotton and other plant species.
Salt-Induced Stress Stimulates a Lipoteichoic Acid-Specific Three-Component Glycosylation System in Staphylococcus aureus

ABSTRACT Lipoteichoic acid (LTA) in Staphylococcus aureus is a poly-glycerophosphate polymer anchored to the outer surface of the cell membrane. LTA has numerous roles in cell envelope physiology, including regulating cell autolysis, coordinating cell division, and adapting to environmental growth conditions. LTA is often further modified with substituents, including d-alanine and glycosyl groups, to alter cellular function. While the genetic determinants of d-alanylation have been largely defined, the route of LTA glycosylation and its role in cell envelope physiology have remained unknown, in part due to the low levels of basal LTA glycosylation in S. aureus. We demonstrate here that S. aureus utilizes a membrane-associated three-component glycosylation system composed of an undecaprenol (Und) N-acetylglucosamine (GlcNAc) charging enzyme (CsbB; SAOUHSC_00713), a putative flippase to transport loaded substrate to the outside surface of the cell (GtcA; SAOUHSC_02722), and finally an LTA-specific glycosyltransferase that adds α-GlcNAc moieties to LTA (YfhO; SAOUHSC_01213). We demonstrate that this system is specific for LTA with no cross recognition of the structurally similar polyribitol phosphate containing wall teichoic acids. We show that while wild-type S. aureus LTA has only a trace of GlcNAcylated LTA under normal growth conditions, amounts are raised upon either overexpressing CsbB, reducing endogenous d-alanylation activity, expressing the cell envelope stress responsive alternative sigma factor SigB, or by exposure to environmental stress-inducing culture conditions, including growth media containing high levels of sodium chloride. IMPORTANCE The role of glycosylation in the structure and function of Staphylococcus aureus lipoteichoic acid (LTA) is largely unknown. By defining key components of the LTA three-component glycosylation pathway and uncovering stress-induced regulation by the alternative sigma factor SigB, the role of N-acetylglucosamine tailoring during adaptation to environmental stresses can now be elucidated. As the dlt and glycosylation pathways compete for the same sites on LTA and induction of glycosylation results in decreased d-alanylation, the interplay between the two modification systems holds implications for resistance to antibiotics and antimicrobial peptides.
Developments in Microencapsulation Technology to Improve Adhesive Formulations

Controlled release of additives and adhesives at the right place and the right time is a key functionality that can be provided by microencapsulation technology. A timely and targeted release improves the effectiveness of additives and adhesives, broadens their application range, and ensures optimal dosage, thereby improving cost-effectiveness for the adhesive manufacturer. Reactive, sensitive, or volatile additives (catalysts, prepolymers, solvents, antioxidants, preservatives, adhesion promoters, biocides, flame retardants, dyes, etc), as well as the total formulation of the adhesive, can be turned into stable ones through microencapsulation. With carefully fine-tuned controlled release properties, microencapsulation is no longer just an added value technique, but the source of totally new products with matchless properties. Nevertheless, although it offers great potential in the adhesive and sealants industry, very little development has been carried out to date in this field. Therefore, the aim of the present literature review paper is to present microencapsulation technique as an interesting option for the adhesive industry as its application can transform traditionally used adhesives into smart or multifunctional ones.
A novel gene‐family involved in spermatophore generation in the economically important salmon louse Lepeophtheirus salmonis

The salmon louse (Lepeophtheirus salmonis) is an important parasite of Atlantic salmon (Salmo salar). It is widely spread in aquaculture facilities and leads to economic losses every year. As it has developed resistances against many common treatments, new control methods must be established. Here we characterize a novel gene family of the salmon louse, consisting of two genes, which has not been described in other species before. We analyzed temporal expression patterns of both genes, the localization of mRNA and protein. An RNAi mediated gene knockdown lead to information about the function of the protein. Overall, these two genes are expressed only in sperm ducts of male sea lice. The mucin‐like proteins can additionally be found in the wall of spermatophores, which are responsible for sperm transfer to females. Knockdown showed that both genes are essential for successful fertilization of females. Overall, all results indicate that the two analyzed genes are necessary for reproduction in sea lice as they are essential for the formation of a wall surrounding the spermatophores, which is needed for fertilization. Therefore, we name them Mucin‐like spermatophore wall protein 1 & 2 (MLSWP1 & MLSWP2). Analysis of sequence data from other copepod species suggests that MLSWPs are present in many copepod species and may also play a similar role in reproduction in those species.
Associations Between Maternal Prepregnancy Body Mass Index and Gestational Weight Gain and Daughter’s Age at Menarche

Abstract Earlier puberty and menarche are associated with adverse health outcomes. Reported associations of maternal adiposity with daughter’s age at menarche are inconsistent. We examined associations between maternal prepregnancy body mass index (BMI; weight (kg)/height (m)2) and gestational weight gain (GWG) and daughter’s ages at menarche (n = 3,935 mother-offspring pairs), pubarche (Tanner stage 2 for pubic hair) (n = 2,942 pairs), and thelarche (Tanner stage 2 for breast development) (n = 2,942 pairs) in the Avon Longitudinal Study of Parents and Children, a prospective United Kingdom pregnancy cohort study (baseline 1991–1992). During a follow-up period of up to 17 years (1991–2008), mean menarcheal age was 12.6 (standard deviation, 1.2) years. Both maternal prepregnancy BMI and GWG were inversely associated with daughter’s age at menarche after adjustment for maternal age, parity, socioeconomic status, smoking, maternal menarcheal age, and ethnicity (mean differences were −0.34 months (95% confidence interval: −0.45, −0.22) per BMI unit and −0.17 months (95% confidence interval: −0.26, −0.07) per kg, respectively). Associations remained unchanged after adjustment for birth weight and gestational age but were attenuated to the null when results were adjusted for daughter’s prepubertal BMI. Similar results were found for ages at pubarche and thelarche. These findings indicate that greater prepregnancy BMI and GWG are associated with earlier puberty in daughters and that these associations are mediated by daughters’ prepubertal BMIs.
Testing our understanding of Arctic denitrification using MIPAS-E satellite measurements in winter 2002/2003

Observations of gas-phase HNO 3 and N 2 O in the polar stratosphere from the Michelson Interferometer for Passive Atmospheric Sounding aboard the ENVISAT satellite (MIPAS-E) were made during the cold Arctic winter of 2002/2003. Vortex temperatures were unusually low in early winter and remained favourable for polar stratospheric cloud formation and denitrification until mid-January. MIPAS-E observations provide the first dataset with sufficient coverage of the polar vortex in mid-winter which enables a reasonable estimate of the timing of onset and spatial distribution of denitrification of the Arctic lower stratosphere to be performed. We use the observations from MIPAS-E to test the evolution of denitrification in the DLAPSE (Denitrification by Lagrangian Particle Sedimentation) microphysical denitrification model coupled to the SLIMCAT chemical transport model. In addition, the predicted denitrification from a simple equilibrium nitric acid trihydrate-based scheme is also compared with MIPAS-E. Modelled denitrification is compared with in-vortex NO y and N 2 O observations from the balloon-borne MarkIV interferometer in mid-December. Denitrification was clearly observed by MIPAS-E in mid-December 2002 and reached 80% in the core of the vortex by early January 2003. The DLAPSE model is broadly able to capture both the timing of onset and the spatial distribution of the observed denitrification. A simple thermodynamic equilibrium scheme is able to reproduce the observed denitrification in the core of the vortex but overestimates denitrification closer to the vortex edge. This study also suggests that the onset of denitrification in simple thermodynamic schemes may be earlier than in the MIPAS-E observations.
Fate and Persistence of a Pathogenic NDM-1-Positive Escherichia coli Strain in Anaerobic and Aerobic Sludge Microcosms

ABSTRACT The presence of emerging biological pollutants in treated wastewater effluents has gained attention due to increased interest in water reuse. To evaluate the effectiveness of the removal of such contaminants by the conventional wastewater treatment process, the fate and decay kinetics of NDM-1-positive Escherichia coli strain PI7 and its plasmid-encoded antibiotic resistance genes (ARGs) were assessed in microcosms of anaerobic and aerobic sludge. Results showed that E. coli PI7 decayed at a significantly lower rate under anaerobic conditions. Approximate half-lives were 32.4 ± 1.4 h and 5.9 ± 0.9 h in the anaerobic and aerobic microcosms, respectively. In the aerobic microcosms, after 72 h of operation, E. coli PI7 remained detectable, but no further decay was observed. Instead, 1 in every 10,000 E. coli cells was identified to be recalcitrant to decay and persist indefinitely in the sludge. ARGs associated with the E. coli PI7 strain were detected to have transferred to other native microorganisms in the sludge or were released to the liquid fraction upon host decay. Extracellular DNA quickly degraded in the liquid fraction of the aerobic sludge. In contrast, no DNA decay was detected in the anaerobic sludge water matrix throughout the 24-h sampling period. This study suggests an increased likelihood of environmental dispersion of ARGs associated with anaerobically treated wastewater effluents and highlights the potential importance of persister cells in the dissemination of E. coli in the environment during reuse events of treated wastewater. IMPORTANCE This study examines the decay kinetics of a pathogenic and antibiotic resistant strain of Escherichia coli in microcosms simulating biological treatment units of aerobic and anaerobic sludge. The results of this study point at a significantly prolonged persistence of the E. coli and the associated antibiotic resistance gene in the anaerobic sludge. However, horizontal transfer of the plasmid encoding the antibiotic resistance gene was detected in the aerobic sludge by a cultivation method. A subpopulation of persister E. coli cells was also detected in the aerobic sludge. The findings of this study suggest potential areas of concern arising from pathogenic and antibiotic-resistant E. coli during both anaerobic and aerobic sludge treatment processes.
Workload-Aware Revenue Maximization in SDN-Enabled Data Center

Nowadays many companies and organizations choose to deploy their applications in data centers to leverage resource sharing. The increase in tasks of multiple applications, however, makes it challenging for a data center provider to maximize its revenue by intelligently scheduling tasks in software-defined networking (SDN)-enabled data centers. Existing SDN controllers only reduce network latency while ignoring virtual machine (VM) latency, thus may lead to revenue loss. In the context of SDN-enabled data centers, this paper presents a workload-aware revenue maximization (WARM) approach to maximize the revenue from a data center provider's perspective. The core idea is to jointly consider the optimal combination of VMs and routing paths for tasks of each application. Comparing with state-of-the-art methods, the experimental results show that WARM yields the best schedules that not only increase the revenue but also reduce the round-trip time of tasks of all applications.
Understanding the variation of friction coefficients of human skin as a function of skin hydration and interfacial water films

Human skin is characterised by a complex and highly variable friction behaviour. Although the variation of friction coefficients measured for skin depends on numerous parameters related to the skin itself, the surface in contact as well as contact conditions, water or sweat – either bound in the stratum corneum and manifest as skin hydration or in form of liquid films lubricating the interface – is the most important factor. Here, we analyse the variation of previous experimental data on the basis of the adhesion friction model and show how lower and upper bounds, i.e. envelope functions, can be derived for measured skin-friction coefficients. From these envelope functions, essential tribological parameters such as the interfacial shear strength and the real contact area of skin are estimated.