Miracle-dz/UniFAR-FTUs huggingface dataset:
Spaceflight Enhances Cell Aggregation and Random Budding in Candida albicans

This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans–induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public.
Directions Toward Effective Utilization of Tactile Skin: A Review

A wide variety of tactile (touch) sensors exist today for robotics and related applications. They make use of various transduction methods, smart materials and engineered structures, complex electronics, and sophisticated data processing. While highly useful in themselves, effective utilization of tactile sensors in robotics applications has been slow to come and largely remains elusive today. This paper surveys the state of the art and the research issues in this area, with the emphasis on effective utilization of tactile sensors in robotic systems. One specific with the use of tactile sensing in robotics is that the sensors have to be spread along the robot body, the way the human skin is-thus dictating varied 3-D spatio-temporal requirements, decentralized and distributed control, and handling of multiple simultaneous tactile contacts. Satisfying these requirements pose challenges to making tactile sensor modality a reality. Overcoming these challenges requires dealing with issues such as sensors placement, electronic/mechanical hardware, methods to access and acquire signals, automatic calibration techniques, and algorithms to process and interpret sensing data in real time. We survey this field from a system perspective, recognizing the fact that the system performance tends to depend on how its various components are put together. It is hoped that the survey will be of use to practitioners designing tactile sensing hardware (whole-body or large-patch sensor coverage), and to researchers working on cognitive robotics involving tactile sensing.
The Role of Dendritic Cells in Central Tolerance

Dendritic cells (DCs) play a significant role in establishing self-tolerance through their ability to present self-antigens to developing T cells in the thymus. DCs are predominantly localized in the medullary region of thymus and present a broad range of self-antigens, which include tissue-restricted antigens expressed and transferred from medullary thymic epithelial cells, circulating antigens directly captured by thymic DCs through coticomedullary junction blood vessels, and peripheral tissue antigens captured and transported by peripheral tissue DCs homing to the thymus. When antigen-presenting DCs make a high affinity interaction with antigen-specific thymocytes, this interaction drives the interacting thymocytes to death, a process often referred to as negative selection, which fundamentally blocks the self-reactive thymocytes from differentiating into mature T cells. Alternatively, the interacting thymocytes differentiate into the regulatory T (Treg) cells, a distinct T cell subset with potent immune suppressive activities. The specific mechanisms by which thymic DCs differentiate Treg cells have been proposed by several laboratories. Here, we review the literatures that elucidate the contribution of thymic DCs to negative selection and Treg cell differentiation, and discusses its potential mechanisms and future directions.
Molecular docking study of P4-Benzoxaborolesubstituted ligands as inhibitors of HCV NS3/4A protease

NS3/4A protease is an important emerging target for the cure of hepatitis C. There are many inhibitors of HCV NS3/4A protease that are passing through the clinical improvement indicating momentous reduction in the viral infection rate of patients. In this study molecular docking via MOE-Dock program was used to evaluate binding interactions of ligands with HCV NS3/4A protease. The docking and experimental results were found in good correlation. The best conformations of ligands were analyzed for binding interactions with the residues of binding cavity of NS3/4A protease. The valuable binding interactions and docking scores were observed for compounds 01, 05, 06, 07, 08 and 09.
Predicting the efficacy of short oligonucleotides in antisense and RNAi experiments with boosted genetic programming

Motivation: Both small interfering RNAs (siRNAs) and antisense oligonucleotides can selectively block gene expression. Although the two methods rely on different cellular mechanisms, these methods share the common property that not all oligonucleotides (oligos) are equally effective. That is, if mRNA target sites are picked at random, many of the antisense or siRNA oligos will not be effective. Algorithms that can reliably predict the efficacy of candidate oligos can greatly reduce the cost of knockdown experiments, but previous attempts to predict the efficacy of antisense oligos have had limited success. Machine learning has not previously been used to predict siRNA efficacy. Results: We develop a genetic programming based prediction system that shows promising results on both antisense and siRNA efficacy prediction. We train and evaluate our system on a previously published database of antisense efficacies and our own database of siRNA efficacies collected from the literature. The best models gave an overall correlation between predicted and observed efficacy of 0.46 on both antisense and siRNA data. As a comparison, the best correlations of support vector machine classifiers trained on the same data were 0.40 and 0.30, respectively. Availability: The prediction system uses proprietary hardware and is available for both commercial and strategic academic collaborations. The siRNA database is available upon request.
Deterministic MAC access control scheme for industrial hybrid IEEE 802.3/IEEE 802.11 networks

In industrial automation systems, the introduction of wireless networks as an extension of the existing wired networks is increasing. However, with the existing wireless technologies, it is impossible to guarantee this coexistence for those applications with strict real-time and reliability requirements such as Networked Control Systems (NCS) or Distributed Control Systems (DCS). The main problem lies in the design of the Medium Access Control (MAC) protocol, as this plays a key role in fulfilling real-time and deterministic requirements. Moreover, the integration of both networks is fundamental to provide a seamless coexistence guaranteeing the demanding requirements of these applications. So, in order to expand the wired network used in NCS to a wireless domain, a hybrid IEEE 802.3/IEEE 802.11 real-time TDMA-based MAC scheme is proposed in this paper. The proposed scheme can support the transmission of periodic real-time traffic and aperiodic real-time traffic in a deterministic way, together with best-effort (BE) traffic. Moreover, with the aim of increasing the reliability of the communication system, retransmission mechanisms are defined. The performance of these MAC schemes has been evaluated over Rayleigh fading channel through OMNeT++ simulator. Provided results show that the transmission of periodic real-time traffic is not affected by the transmission of aperiodic or BE traffic. Moreover, results show that the transmissions and retransmissions are adapted to tight control cycles.
Production of an electrolyte beverage from milk permeate.

The objective of this study was to prepare shelf-stable electrolyte beverages from milk permeate. The average composition of permeate was 4.59% total solids and . 40% ash. Lactose was hydrolyzed (approximately 80%) with a commercial fungal lactase enzyme. Additional sweetness was provided by sucrose. The pH was reduced to 3.5 to 3.8 by the addition of citric acid. Shelf-stable products were made using four processes: 1) UHT followed by aseptic filling, 2) heating of filled bottles to 85 degrees C for 30 min, 3) addition of . 05% benzoate, and 4) nanopore filtration. The mineral composition of the finished product, expressed in parts per million, was calcium, 150; phosphorus, 157; magnesium, 43; potassium, 1166; sodium, 286; iron, 17; copper, 8; and zinc, 3.4. Listeria monocytogenes, Salmonella dublin, Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, and Streptococcus agalactiae grew well when they were inoculated into unacidified, hydrolyzed permeate. None of these organisms were isolated from properly processed products. A shelf-stable electrolyte beverage high in minerals was made from whole milk permeate. This beverage could be used to replace electrolytes lost from the human body. The production of a permeate beverage would help alleviate disposal problems of permeate.
Horizontal transfer of facultative endosymbionts is limited by host relatedness

Heritable microbial symbionts can have important effects on many aspects of their hosts’ biology. Acquisition of a novel symbiont strain can provide fitness benefits to the host, with significant ecological and evolutionary consequences. We measured barriers to horizontal transmission by artificially transferring facultative symbionts from the grain aphid, Sitobion avenae, and five other aphid species into two clonal genotypes of S. avenae. We found the symbiont Hamiltonella defensa establishes infections more easily following a transfer from the same host species and that such infections are more stable. Infection success was also higher when the introduced symbiont strain was more closely related to the strain that was originally present in the host (but which had previously been removed). There were no differences among successfully established symbiont strains in their effect on aphid fecundity. Hamiltonella defensa did not confer protection against parasitoids in our S. avenae clones, although it often does in other aphid hosts. However, strains of the symbiont Regiella insecticola originating from two host species protected grain aphids against the pathogenic fungus Pandora neoaphidis. This study helps describe the extent to which facultative symbionts can act as a pool of adaptations that can be sampled by their eukaryote hosts.
Activation of BK and SK Channels by Efferent Synapses on Outer Hair Cells in High-Frequency Regions of the Rodent Cochlea

Cholinergic neurons of the brainstem olivary complex project to and inhibit outer hair cells (OHCs), refining acoustic sensitivity of the mammalian cochlea. In all vertebrate hair cells studied to date, cholinergic inhibition results from the combined action of ionotropic acetylcholine receptors and associated calcium-activated potassium channels. Although inhibition was thought to involve exclusively small conductance (SK potassium channels), recent findings have shown that BK channels also contribute to inhibition in basal, high-frequency OHCs after the onset of hearing. Here we show that the waveform of randomly timed IPSCs (evoked by high extracellular potassium) in high-frequency OHCs is altered by blockade of either SK or BK channels, with BK channels supporting faster synaptic waveforms and SK channels supporting slower synaptic waveforms. Consistent with these findings, IPSCs recorded from high-frequency OHCs that express BK channels are briefer than IPSCs recorded from low-frequency (apical) OHCs that do not express BK channels and from immature high-frequency OHCs before the developmental onset of BK channel expression. Likewise, OHCs of BKα−/− mice lacking the pore-forming α-subunit of BK channels have longer IPSCs than do the OHCs of BKα+/+ littermates. Furthermore, serial reconstruction of electron micrographs showed that postsynaptic cisterns of BKα−/− OHCs were smaller than those of BKα+/+ OHCs, and immunofluorescent quantification showed that efferent presynaptic terminals of BKα−/− OHCs were smaller than those of BKα+/+ OHCs. Together, these findings indicate that BK channels contribute to postsynaptic function, and influence the structural maturation of efferent-OHC synapses.
Magnetic Resonance Imaging of Tumors Colonized with Bacterial Ferritin-Expressing Escherichia coli

Background Recent studies have shown that human ferritin can be used as a reporter of gene expression for magnetic resonance imaging (MRI). Bacteria also encode three classes of ferritin-type molecules with iron accumulation properties. Methods and Findings Here, we investigated whether these bacterial ferritins can also be used as MRI reporter genes and which of the bacterial ferritins is the most suitable reporter. Bacterial ferritins were overexpressed in probiotic E. coli Nissle 1917. Cultures of these bacteria were analyzed and those generating highest MRI contrast were further investigated in tumor bearing mice. Among members of three classes of bacterial ferritin tested, bacterioferritin showed the most promise as a reporter gene. Although all three proteins accumulated similar amounts of iron when overexpressed individually, bacterioferritin showed the highest contrast change. By site-directed mutagenesis we also show that the heme iron, a unique part of the bacterioferritin molecule, is not critical for MRI contrast change. Tumor-specific induction of bacterioferritin-expression in colonized tumors resulted in contrast changes within the bacteria-colonized tumors. Conclusions Our data suggest that colonization and gene expression by live vectors expressing bacterioferritin can be monitored by MRI due to contrast changes.
Naming the pain in requirements engineering: design of a global family of surveys and first results from Germany

Context: For many years, we have observed industry struggling in defining a high quality requirements engineering (RE) and researchers trying to understand industrial expectations and problems. Although we are investigating the discipline with a plethora of empirical studies, those studies either concentrate on validating specific methods or on single companies or countries. Therefore, they allow only for limited empirical generalisations. Objective: To lay an empirical and generalisable foundation about the state of the practice in RE, we aim at a series of open and reproducible surveys that allow us to steer future research in a problem-driven manner. Method: We designed a globally distributed family of surveys in joint collaborations with different researchers from different countries. The instrument is based on an initial theory inferred from available studies. As a long-term goal, the survey will be regularly replicated to manifest a clear understanding on the status quo and practical needs in RE. In this paper, we present the design of the family of surveys and first results of its start in Germany. Results: Our first results contain responses from 30 German companies. The results are not yet generalisable, but already indicate several trends and problems. For instance, a commonly stated problem respondents see in their company standards are artefacts being underrepresented, and important problems they experience in their projects are incomplete and inconsistent requirements. Conclusion: The results suggest that the survey design and instrument are well-suited to be replicated and, thereby, to create a generalisable empirical basis of RE in practice.
Hyponatremia, Cognitive Function, and Mobility in an Outpatient Heart Failure Population

Background The association of hyponatremia with cognitive impairment and mobility in heart failure (HF) patients is unknown. The purpose of this study was to determine if hyponatremia is associated with cognitive and mobility impairment as measured by simple, validated, and time-sensitive tests. Material/Methods This was a prospective study in patients with reduced and preserved ejection fraction (HFrEF, HFpEF) seen in outpatient HF clinics. Hyponatremia was defined as sodium level ≤136 mEq/L. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) tool, and mobility was measured with the Timed Up and Go test (TUG-t). Results A total of 121 patients were evaluated; 30% were hyponatremic (134±1.9 mEq/l, range 128–136 mEq/l). Overall, 92% of hyponatremic patients had cognitive impairment (MoCA <26) compared to 76% of the non-hyponatremic patients [relative risk 1.2 (confidence interval: 1.02–1.4, p=0.02)]. In regard to mobility, 72% of hyponatremic patients and 62% of non-hyponatremic patients (p=0.4) had TUG-t times that were considered to be worse than average. A total of 84% (N=76) of HFrEF and 71% (N=22) of HFpEF patients had cognitive impairment (p=0.86). HFrEF patients had significantly lower overall MoCA scores (21.2±3.7 vs. 23.3±3.6, p=0.006) and similar TUG-t times compared to HFpEF patients. Conclusions Most heart failure patients (HFrEF and HFpEF) seen in an ambulatory setting had impairment of cognitive function and mobility, with a higher prevalence among those with hyponatremia. Screening can be done using tests that can be administered in a clinical setting.
Histone Deacetylases 1 and 2 Form a Developmental Switch That Controls Excitatory Synapse Maturation and Function

The structural assembly of synapses can be accomplished in a rapid time frame, although most nascent synapses formed during early development are not fully functional and respond poorly to presynaptic action potentials. The mechanisms that are responsible for this delay in synapse maturation are unknown. Histone deacetylases (HDACs) regulate the activity state of chromatin and repress gene expression through the removal of acetyl groups from histones. Class I HDACs, which include HDAC1 and HDAC2, are expressed in the CNS, although their specific role in neuronal function has not been studied. To delineate the contribution of HDAC1 and HDAC2 in the brain, we have used pharmacological inhibitors of HDACs and mice with conditional alleles to HDAC1 and HDAC2. We found that a decrease in the activities of both HDAC1 and HDAC2 during early synaptic development causes a robust facilitation of excitatory synapse maturation and a modest increase in synapse numbers. In contrast, in mature neurons a decrease in HDAC2 levels alone was sufficient to attenuate basal excitatory neurotransmission without a significant change in the numbers of detectable nerve terminals. Therefore, we propose that HDAC1 and HDAC2 form a developmental switch that controls synapse maturation and function acting in a manner dependent on the maturational states of neuronal networks.
Short-Lived Effector CD8 T Cells Induced by Genetically Attenuated Malaria Parasite Vaccination Express CD11c

ABSTRACT Vaccination with a single dose of genetically attenuated malaria parasites can induce sterile protection against sporozoite challenge in the rodent Plasmodium yoelii model. Protection is dependent on CD8+ T cells, involves perforin and gamma interferon (IFN-γ), and is correlated with the expansion of effector memory CD8+ T cells in the liver. Here, we have further characterized vaccine-induced changes in the CD8+ T cell phenotype and demonstrated significant upregulation of CD11c on CD3+ CD8b+ T cells in the liver, spleen, and peripheral blood. CD11c+ CD8+ T cells are predominantly CD11ahi CD44hi CD62L−, indicative of antigen-experienced effector cells. Following in vitro restimulation with malaria-infected hepatocytes, CD11c+ CD8+ T cells expressed inflammatory cytokines and cytotoxicity markers, including IFN-γ, tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), perforin, and CD107a. CD11c− CD8+ T cells, on the other hand, expressed negligible amounts of all inflammatory cytokines and cytotoxicity markers tested, indicating that CD11c marks multifunctional effector CD8+ T cells. Coculture of CD11c+, but not CD11c−, CD8+ T cells with sporozoite-infected primary hepatocytes significantly inhibited liver-stage parasite development. Tetramer staining for the immunodominant circumsporozoite protein (CSP)-specific CD8+ T cell epitope demonstrated that approximately two-thirds of CSP-specific cells expressed CD11c at the peak of the CD11c+ CD8+ T cell response, but CD11c expression was lost as the CD8+ T cells entered the memory phase. Further analyses showed that CD11c+ CD8+ T cells are primarily KLRG1+ CD127− terminal effectors, whereas all KLRG1− CD127+ memory precursor effector cells are CD11c− CD8+ T cells. Together, these results suggest that CD11c marks a subset of highly inflammatory, short-lived, antigen-specific effector cells, which may play an important role in eliminating infected hepatocytes.
Resolving “This-issue” Anaphora

We annotate and resolve a particular case of abstract anaphora, namely, this-issue anaphora. We propose a candidate ranking model for this-issue anaphora resolution that explores different issue-specific and general abstract-anaphora features. The model is not restricted to nominal or verbal antecedents; rather, it is able to identify antecedents that are arbitrary spans of text. Our results show that (a) the model outperforms the strong adjacent-sentence baseline; (b) general abstract-anaphora features, as distinguished from issue-specific features, play a crucial role in this-issue anaphora resolution, suggesting that our approach can be generalized for other NPs such as this problem and this debate; and (c) it is possible to reduce the search space in order to improve performance.