Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychometric augmentation of an interactive genetic algorithm for optimizing cochlear implant programs

As suggested in the Blind Watchmaker, human selection can be a remarkable source of information for guiding a genetic algorithm when objective cost functions are unknown. Properly harnessing such input, however, requires an understanding of the "numbers" humans produce as well as the limitations humans face when performing extensive judgment tasks. The Interactive Augmented Genetic Algorithm (IAGA) modifies both the procedural and algorithmic components of Interactive Genetic Algorithms to better match the human-selection process. experimental results show that cochlear implant recipients are successful in using the IAGA to select processing parameters to improve their perception of music.
Neurons Controlling Aplysia Feeding Inhibit Themselves by Continuous NO Production

Background Neural activity can be affected by nitric oxide (NO) produced by spiking neurons. Can neural activity also be affected by NO produced in neurons in the absence of spiking? Methodology/Principal Findings Applying an NO scavenger to quiescent Aplysia buccal ganglia initiated fictive feeding, indicating that NO production at rest inhibits feeding. The inhibition is in part via effects on neurons B31/B32, neurons initiating food consumption. Applying NO scavengers or nitric oxide synthase (NOS) blockers to B31/B32 neurons cultured in isolation caused inactive neurons to depolarize and fire, indicating that B31/B32 produce NO tonically without action potentials, and tonic NO production contributes to the B31/B32 resting potentials. Guanylyl cyclase blockers also caused depolarization and firing, indicating that the cGMP second messenger cascade, presumably activated by the tonic presence of NO, contributes to the B31/B32 resting potential. Blocking NO while voltage-clamping revealed an inward leak current, indicating that NO prevents this current from depolarizing the neuron. Blocking nitrergic transmission had no effect on a number of other cultured, isolated neurons. However, treatment with NO blockers did excite cerebral ganglion neuron C-PR, a command-like neuron initiating food-finding behavior, both in situ, and when the neuron was cultured in isolation, indicating that this neuron also inhibits itself by producing NO at rest. Conclusion/Significance Self-inhibitory, tonic NO production is a novel mechanism for the modulation of neural activity. Localization of this mechanism to critical neurons in different ganglia controlling different aspects of a behavior provides a mechanism by which a humeral signal affecting background NO production, such as the NO precursor L-arginine, could control multiple aspects of the behavior.
The Lung Microbiota of Healthy Mice Are Highly Variable, Cluster by Environment, and Reflect Variation in Baseline Lung Innate Immunity

Rationale: The “gut‐lung axis” is commonly invoked to explain the microbiome's influence on lung inflammation. Yet the lungs harbor their own microbiome, which is altered in respiratory disease. The relative influence of gut and lung bacteria on lung inflammation is unknown. Objectives: To determine whether baseline lung immune tone reflects local (lung‐lung) or remote (gut‐lung) microbe‐host interactions. Methods: We compared lung, tongue, and cecal bacteria in 40 healthy, genetically identical, 10‐week‐old mice, using 16S ribosomal RNA gene quantification and sequencing. We measured inflammatory cytokines, using a multiplex assay of homogenized lung tissue. We compared lung bacteria in healthy mice treated with varied durations of systemic antibiotics. Measurements and Main Results: Lung bacterial communities are highly variable among mice, cluster strongly by cage, shipment, and vendor, and are altered by antibiotics in a microbiologically predictable manner. Baseline lung concentrations of two key inflammatory cytokines (IL‐1&agr; and IL‐4) are correlated with the diversity and community composition of lung bacterial communities. Lung concentrations of these inflammatory cytokines correlate more strongly with variation in lung bacterial communities than with that of the gut or mouth. Conclusions: In the lungs of healthy mice, baseline innate immune tone more strongly reflects local (lung‐lung) microbe‐host interactions than remote (gut‐lung) microbe‐host interactions. Our results independently confirm the existence and immunologic significance of the murine lung microbiome, even in health. Variation in lung microbiota is likely an important, underappreciated source of experimental and clinical variability. The lung microbiome is an unexplored therapeutic target for the prevention and treatment of inflammatory lung disease.
The Effect of Metformin on Serum Gonadotropin Levels in Postmenopausal Women with Diabetes and Prediabetes: A Pilot Study

Abstract Background Metformin was found to decrease serum levels of prolactin and thyrotropin. The aim of this study was to investigate the effect of this drug on hypothalamic-pituitary-ovarian axis activity in postmenopausal women with recently diagnosed and untreated glucose metabolism abnormalities. Methods The study included three matched groups of postmenopausal women: patients with type 2 diabetes (group A, n=16), women with prediabetes (group B, n=14), and individuals with normal glucose metabolism (group C, n=14). Women with diabetes were then treated with high-dose metformin (3 g daily), while women with prediabetes received moderate doses of this agent (1.7 g daily). Glucose homeostasis markers, as well as serum levels of FSH, LH, thyrotropin, prolactin, estradiol and creatinine were measured at baseline and after 16 weeks of metformin treatment. Results In both groups of metformin-treated women, the drug improved glucose homeostasis. High-dose metformin treatment reduced circulating levels of FSH and tended to reduce serum levels of LH, and these effects correlated with an improvement in insulin sensitivity. No changes in gonadotropin levels were observed in prediabetic women receiving moderate doses of metformin. Serum levels of thyrotropin, prolactin and estradiol, as well as the estimated glomerular filtration rate remained at a similar level throughout the study. Conclusions Our study shows that the effect of metformin on hypothalamic-pituitary-ovarian axis activity in postmenopausal women depends on its dose and the magnitude of insulin resistance.
Context-Derived Pseudonyms for Protection of Privacy in Transport Middleware and Applications

This paper outlines why context-aware transport applications necessarily record information about people and describes how we can use anonymity techniques to minimise the resulting invasion of privacy. In particular we: (i) describe how to generate unlinkable personal pseudonyms; (ii) describe a method of creating group pseudonyms (an opaque pseudonym representing several individuals); and (iii) describe how to store these pseudonyms safely in a database. We go on to present two sample transport applications which utilise our technique and suggest areas for future work
Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during Current or Convalescent Plasmodium falciparum Infection in Malawian Children

ABSTRACT Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with Plasmodium falciparum infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that P. falciparum infection compromises the humoral and cellular immunity of the host to NTS, which increases the susceptibility of the host to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi, and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria negative, and nonfebrile malaria negative. Levels of Salmonella enterica serovar Typhimurium-specific serum bactericidal activity (SBA) and whole-blood bactericidal activity (WBBA), complement C3 deposition, and neutrophil respiratory burst activity (NRBA) were measured. Levels of SBA with respect to S. Typhimurium were reduced in febrile P. falciparum-infected children (median, −0.20 log10 [interquartile range {IQR}, −1.85, 0.32]) compared to nonfebrile malaria-negative children (median, −1.42 log10 [IQR, −2.0, −0.47], P = 0.052). In relation to SBA, C3 deposition on S. Typhimurium was significantly reduced in febrile P. falciparum-infected children (median, 7.5% [IQR, 4.1, 15.0]) compared to nonfebrile malaria-negative children (median, 29% [IQR, 11.8, 48.0], P = 0.048). WBBA with respect to S. Typhimurium was significantly reduced in febrile P. falciparum-infected children (median, 0.25 log10 [IQR, −0.73, 1.13], P = 0.0001) compared to nonfebrile malaria-negative children (median, −1.0 log10 [IQR, −1.68, −0.16]). In relation to WBBA, S. Typhimurium-specific NRBA was reduced in febrile P. falciparum-infected children (median, 8.8% [IQR, 3.7, 20], P = 0.0001) compared to nonfebrile malaria-negative children (median, 40.5% [IQR, 33, 65.8]). P. falciparum infection impairs humoral and cellular immunity to S. Typhimurium in children during malaria episodes, which may explain the increased risk of iNTS observed in children from settings of malaria endemicity. The mechanisms underlying humoral immunity impairment are incompletely understood and should be explored further.
Action Prediction Allows Hypothesis Testing via Internal Forward Models at 6 Months of Age

We propose that action prediction provides a cornerstone in a learning process known as internal forward models. According to this suggestion infants’ predictions (looking to the mouth of someone moving a spoon upward) will moments later be validated or proven false (spoon was in fact directed toward a bowl), information that is directly perceived as the distance between the predicted and actual goal. Using an individual difference approach we demonstrate that action prediction correlates with the tendency to react with surprise when social interactions are not acted out as expected (action evaluation). This association is demonstrated across tasks and in a large sample (n = 118) at 6 months of age. These results provide the first indication that infants might rely on internal forward models to structure their social world. Additional analysis, consistent with prior work and assumptions from embodied cognition, demonstrates that the latency of infants’ action predictions correlate with the infant’s own manual proficiency.
Lizards Cooperatively Tunnel to Construct a Long-Term Home for Family Members

Constructing a home to protect offspring while they mature is common in many vertebrate groups, but has not previously been reported in lizards. Here we provide the first example of a lizard that constructs a long-term home for family members, and a rare case of lizards behaving cooperatively. The great desert skink, Liopholis kintorei from Central Australia, constructs an elaborate multi-tunnelled burrow that can be continuously occupied for up to 7 years. Multiple generations participate in construction and maintenance of burrows. Parental assignments based on DNA analysis show that immature individuals within the same burrow were mostly full siblings, even when several age cohorts were present. Parents were always captured at burrows containing their offspring, and females were only detected breeding with the same male both within- and across seasons. Consequently, the individual investments made to construct or maintain a burrow system benefit their own offspring, or siblings, over several breeding seasons.
A Novel Soluble Immune-Type Receptor (SITR) in Teleost Fish: Carp SITR Is Involved in the Nitric Oxide-Mediated Response to a Protozoan Parasite

Background The innate immune system relies upon a wide range of germ-line encoded receptors including a large number of immunoglobulin superfamily (IgSF) receptors. Different Ig-like immune receptor families have been reported in mammals, birds, amphibians and fish. Most innate immune receptors of the IgSF are type I transmembrane proteins containing one or more extracellular Ig-like domains and their regulation of effector functions is mediated intracellularly by distinct stimulatory or inhibitory pathways. Methodology/Principal Findings Carp SITR was found in a substracted cDNA repertoire from carp macrophages, enriched for genes up-regulated in response to the protozoan parasite Trypanoplasma borreli. Carp SITR is a type I protein with two extracellular Ig domains in a unique organisation of a N-proximal V/C2 (or I-) type and a C-proximal V-type Ig domain, devoid of a transmembrane domain or any intracytoplasmic signalling motif. The carp SITR C-proximal V-type Ig domain, in particular, has a close sequence similarity and conserved structural characteristics to the mammalian CD300 molecules. By generating an anti-SITR antibody we could show that SITR protein expression was restricted to cells of the myeloid lineage. Carp SITR is abundantly expressed in macrophages and is secreted upon in vitro stimulation with the protozoan parasite T. borreli. Secretion of SITR protein during in vivo T. borreli infection suggests a role for this IgSF receptor in the host response to this protozoan parasite. Overexpression of carp SITR in mouse macrophages and knock-down of SITR protein expression in carp macrophages, using morpholino antisense technology, provided evidence for the involvement of carp SITR in the parasite-induced NO production. Conclusion/Significance We report the structural and functional characterization of a novel soluble immune-type receptor (SITR) in a teleost fish and propose a role for carp SITR in the NO-mediated response to a protozoan parasite.
Automated axis alignment for a nano manipulator inside SEM

The consistency between the axis of manipulators and image is very significant since the visual servo is the most important tool in the nano manipulation. This paper proposed an automated axis alignment method for a nano manipulator inside the SEM by recognizing the position of a closed-loop controlled the end-effector, which can characterize the relationship of these two axes and the rotation matrix can be calculated accordingly. The method in this paper can accelerate the process of axis alignment to avoid the electron beam induced deposition effect on the end tips. Experiment demonstration shows it can achieve a 0.1degree precision in 90seconds.
The complete mitochondrial genome of Eumeces chinensis (Squamata: Scincidae) and implications for Scincidae taxonomy

Abstract Chinese skink (Eumeces chinensis) is a ground-dwelling oviparous sincid lizard, which is widely distributed in the southern Provinces of China, including Taiwan and Hainan. Here, the complete mitochondrial genome of E. chinensis (17 175 bp in length) has been analyzed for building the database. It contains 37 genes (13 protein-coding genes, 2 rRNA genes and 22 tRNA genes) and a non-coding region (D-loop). Overall base composition of the complete mitochondrial DNA is A (32.1%), G (14.3%), C (28.8%), and T (24.8%), so the percentage of A and T (56.9%) is slightly higher than G and C (43.1%). All the genes in E. chinensis were distributed on the H-strand, except for the ND6 subunit gene and nine tRNA genes which were encoded on the L-strand. Our phylogeny study shows that E. chinensis and P. egregius are the sister group which belongs to the genus, Plestiodon. In addition, we also prove that Lacertidae is sister to the families, Gekkonidae and Scincidae.
Modular one-to-many clutchable actuator for a soft elbow exosuit

Exoskeletons have been developed for a wide range of applications, from the military to the medical field, with the aim of augmenting human performance or compensating for neuromuscular deficiencies. However, to empower the high number of degrees of freedom of the human body, they often employ a high number of motors, increasing the size, weight and power consumption of the system. We hereby present an actuation strategy to empower our elbow exosuit that adopts a single motor to drive multiple, independently actuated, degrees of freedom. This paradigm, known as One-to-many, is achieved using a modular design where each module comprises a clutchable mechanism that allows to convert a single directional motion from the prime mover to a selectable bidirectional output. Moreover, the mechanism has a locking feature that enables the wearer of the exoskeleton to hold a static load with a minimal power consumption. We present a simple controller for the clutchable unit based on a finite-state machine model, and evaluate its performance for varying input velocities. The system is shown to have a bandwidth of 1.5 Hz, sufficient for daily elbow movements, whilst retaining a compact design.
Characterization of a Unique Tetrasaccharide and Distinct Glycoproteome in the O-Linked Protein Glycosylation System of Neisseria elongata subsp. glycolytica

ABSTRACT Broad-spectrum O-linked protein glycosylation is well characterized in the major Neisseria species of importance to human health and disease. Within strains of Neisseria gonorrhoeae, N. meningitidis, and N. lactamica, protein glycosylation (pgl) gene content and the corresponding oligosaccharide structure are fairly well conserved, although intra- and interstrain variability occurs. The status of such systems in distantly related commensal species, however, remains largely unexplored. Using a strain of deeply branching Neisseria elongata subsp. glycolytica, a heretofore unrecognized tetrasaccharide glycoform consisting of di-N-acetylbacillosamine-glucose-di-N-acetyl hexuronic acid-N-acetylhexosamine (diNAcBac-Glc-diNAcHexA-HexNAc) was identified. Directed mutagenesis, mass spectrometric analysis, and glycan serotyping confirmed that the oligosaccharide is an extended version of the diNAcBac-Glc-based structure seen in N. gonorrhoeae and N. meningitidis generated by the successive actions of PglB, PglC, and PglD and glucosyltransferase PglH orthologues. In addition, a null mutation in the orthologue of the broadly conserved but enigmatic pglG gene precluded expression of the extended glycoform, providing the first evidence that its product is a functional glycosyltransferase. Despite clear evidence for a substantial number of glycoprotein substrates, the major pilin subunit of the endogenous type IV pilus was not glycosylated. The latter finding raises obvious questions as to the relative distribution of pilin glycosylation within the genus, how protein glycosylation substrates are selected, and the overall structure-function relationships of broad-spectrum protein glycosylation. Together, the results of this study provide a foundation upon which to assess neisserial O-linked protein glycosylation diversity at the genus level. IMPORTANCE Broad-spectrum protein glycosylation systems are well characterized in the pathogenic Neisseria species N. gonorrhoeae and N. meningitidis. A number of lines of evidence indicate that the glycan components in these systems are subject to diversifying selection and suggest that glycan variation may be driven in the context of glycosylation of the abundant and surface-localized pilin protein PilE, the major subunit of type IV pili. Here, we examined protein glycosylation in a distantly related, nonpathogenic neisserial species, Neisseria elongata subsp. glycolytica. This system has clear similarities to the systems found in pathogenic species but makes novel glycoforms utilizing a glycosyltransferase that is widely conserved at the genus level but whose function until now remained unknown. Remarkably, PilE pilin is not glycosylated in this species, a finding that raises important questions about the evolutionary trajectories and overall structure-function relationships of broad-spectrum protein glycosylation systems in bacteria.
RNA polymerase II senses obstruction in the DNA minor groove via a conserved sensor motif

Significance Transcription addiction is a hallmark of cancer and a potential therapeutic target. RNA polymerase II (pol II) is responsible for synthesizing precursor mRNA in all eukaryotic cells and can be blocked by obstacles, such as DNA lesions and nucleosomes on the DNA template. In this study, we demonstrate that sequence-specific minor groove binding pyrrole-imidazole polyamides can sterically block an elongating polymerase at the targeted binding site. We find this blockage is persistent and cannot be rescued by transcription factor IIS. We further show pyrrole-imidazole polyamides are detected in the minor groove via two conserved residues in the Switch 1 region of pol II. Collectively, these results provide mechanistic insights on how a noncovalent minor groove binder can obstruct pol II elongation. RNA polymerase II (pol II) encounters numerous barriers during transcription elongation, including DNA strand breaks, DNA lesions, and nucleosomes. Pyrrole-imidazole (Py-Im) polyamides bind to the minor groove of DNA with programmable sequence specificity and high affinity. Previous studies suggest that Py-Im polyamides can prevent transcription factor binding, as well as interfere with pol II transcription elongation. However, the mechanism of pol II inhibition by Py-Im polyamides is unclear. Here we investigate the mechanism of how these minor-groove binders affect pol II transcription elongation. In the presence of site-specifically bound Py-Im polyamides, we find that the pol II elongation complex becomes arrested immediately upstream of the targeted DNA sequence, and is not rescued by transcription factor IIS, which is in contrast to pol II blockage by a nucleosome barrier. Further analysis reveals that two conserved pol II residues in the Switch 1 region contribute to pol II stalling. Our study suggests this motif in pol II can sense the structural changes of the DNA minor groove and can be considered a “minor groove sensor. ” Prolonged interference of transcription elongation by sequence-specific minor groove binders may present opportunities to target transcription addiction for cancer therapy.
Raman spectroscopy using photonic waveguides

We propose and demonstrate the use of CMOS-compatible integrated photonic waveguides for Raman spectroscopy. A droplet of isopropyl alcohol is evanescently excited and detected using single-mode silicon-nitride strip waveguides. Dependence of Raman signal with the length of waveguide is also reported.
Gender dysphoria in adolescence: current perspectives

Increasing numbers of adolescents are seeking treatment at gender identity services in Western countries. An increasingly accepted treatment model that includes puberty suppression with gonadotropin-releasing hormone analogs starting during the early stages of puberty, cross-sex hormonal treatment starting at ~16 years of age and possibly surgical treatments in legal adulthood, is often indicated for adolescents with childhood gender dysphoria (GD) that intensifies during puberty. However, virtually nothing is known regarding adolescent-onset GD, its progression and factors that influence the completion of the developmental tasks of adolescence among young people with GD and/or transgender identity. Consolidation of identity development is a central developmental goal of adolescence, but we still do not know enough about how gender identity and gender variance actually evolve. Treatment-seeking adolescents with GD present with considerable psychiatric comorbidity. There is little research on how GD and/or transgender identity are associated with completion of developmental tasks of adolescence.