Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice

Abnormal sensory responses associated with Fragile X Syndrome (FXS) and autism spectrum disorders include hypersensitivity and impaired habituation to repeated stimuli. Similar sensory deficits are also observed in adult Fmr1 knock-out (KO) mice and are reversed by genetic deletion of Matrix Metalloproteinase-9 (MMP-9) through yet unknown mechanisms. Here we present new evidence that impaired development of parvalbumin (PV)-expressing inhibitory interneurons may underlie hyper-responsiveness in auditory cortex of Fmr1 KO mice via MMP-9-dependent regulation of perineuronal nets (PNNs). First, we found that PV cell development and PNN formation around GABAergic interneurons were impaired in developing auditory cortex of Fmr1 KO mice. Second, MMP-9 levels were elevated in P12-P18 auditory cortex of Fmr1 KO mice and genetic reduction of MMP-9 to WT levels restored the formation of PNNs around PV cells. Third, in vivo single-unit recordings from auditory cortex neurons showed enhanced spontaneous and sound-driven responses in developing Fmr1 KO mice, which were normalized following genetic reduction of MMP-9. These findings indicate that elevated MMP-9 levels contribute to the development of sensory hypersensitivity by influencing formation of PNNs around PV interneurons suggesting MMP-9 as a new therapeutic target to reduce sensory deficits in FXS and potentially other autism spectrum disorders.
Finding all solutions of piecewise-linear resistive circuits using the dual simplex method

An efficient algorithm is proposed for finding all solutions of piecewise-linear (PWL) resistive circuits using linear programming (LP). This algorithm is based on a simple test (termed the LP test) for nonexistence of a solution to a system of PWL equations in a given region. In the LP test, the system of PWL equations is transformed in to an LP problem, to which the simplex method is applied. Such an LP problem is obtained by surrounding the PWL functions by rectangles. In this paper, we introduce the dual simplex method to the LP test, which makes the average number of pivotings per region much smaller (less than one, for example) and makes the algorithm very efficient.
Early Electrophysiological Basis of Experience-Associated Holistic Processing of Chinese Characters

Recent studies have found holistic processing to be a marker of expertise for perception of words in alphabetic (e.g., English) and non-alphabetic (e.g., Chinese) writing systems, consistent with what has been found for faces and other objects of face-like expertise. It is unknown, however, whether holistic processing of words occurs in an early, perceptual stage as it does for faces. We examined how early holistic processing of Chinese characters emerges by recording the event-related potentials (ERPs) in an adaptation paradigm. Participants judged if the top parts of two sequentially presented characters were the same or different while ignoring the bottom part. An early potential (P1) at the posterior channels was smaller when the attended top parts were the same compared with when they are different, indicating an adaptation effect. Critically, for trials with identical top parts, P1 was larger when the irrelevant bottom parts were different, indicating a release of adaptation. This effect was present only when the two character parts were aligned but not misaligned, and only for characters but not for pseudocharacters. The finding of early sensitivity to all parts of a Chinese character suggests that Chinese characters are represented holistically at a perceptual level.
Climate and Soil Type Together Explain the Distribution of Microendemic Species in a Biodiversity Hotspot

The grasshopper genus Caledonula, endemic to New Caledonia, was studied to understand the evolution of species distributions in relation to climate and soil types. Based on a comprehensive sampling of 80 locations throughout the island, the genus was represented by five species, four of which are new to science, of which three are described here. All the species have limited distributions in New Caledonia. Bioclimatic niche modelling shows that all the species were found in association with a wet climate and reduced seasonality, explaining their restriction to the southern half of the island. The results suggest that the genus was ancestrally constrained by seasonality. A molecular phylogeny was reconstructed using two mitochondrial and two nuclear markers. The partially resolved tree showed monophyly of the species found on metalliferous soils, and molecular dating indicated a rather recent origin for the genus. Adaptation to metalliferous soils is suggested by both morphological changes and radiation on these soils. The genus Caledonula is therefore a good model to understand the origin of microendemism in the context of recent and mixed influences of climate and soil type.
Cell Receptor and Cofactor Interactions of the Contact Activation System and Factor XI

The contact activation system (CAS) or contact pathway is central to the crosstalk between coagulation and inflammation and contributes to diverse disorders affecting the cardiovascular system. CAS initiation contributes to thrombosis but is not required for hemostasis and can trigger plasma coagulation via the intrinsic pathway [through factor XI (FXI)] and inflammation via bradykinin release. Activation of factor XII (FXII) is the principal starting point for the cascade of proteolytic cleavages involving FXI, prekallikrein (PK), and cofactor high molecular weight kininogen (HK) but the precise location and cell receptor interactions controlling these reactions remains unclear. FXII, PK, FXI, and HK utilize key protein domains to mediate binding interactions to cognate cell receptors and diverse ligands, which regulates protease activation. The assembly of contact factors has been demonstrated on the cell membranes of a variety of cell types and microorganisms. The cooperation between the contact factors and endothelial cells, platelets, and leukocytes contributes to pathways driving thrombosis yet the basis of these interactions and the relationship with activation of the contact factors remains undefined. This review focuses on cell receptor interactions of contact proteins and FXI to develop a cell-based model for the regulation of contact activation.
Phenotyping of Left and Right Ventricular Function in Mouse Models of Compensated Hypertrophy and Heart Failure with Cardiac MRI

Background Left ventricular (LV) and right ventricular (RV) function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding mouse model. Therefore, we quantified time-dependent alterations in the ventricular morphology and function in two models of hypertrophy and heart failure and we studied the relationship between RV and LV function during the transition from hypertrophy to heart failure. Methods MRI was used to quantify RV and LV function and morphology in healthy (n = 4) and sham operated (n = 3) C57BL/6 mice, and animals with a mild (n = 5) and a severe aortic constriction (n = 10). Results Mice subjected to a mild constriction showed increased LV mass (P<0.01) and depressed LV ejection fraction (EF) (P<0.05) as compared to controls, but had similar RVEF (P>0.05). Animals with a severe constriction progressively developed LV hypertrophy (P<0.001), depressed LVEF (P<0.001), followed by a declining RVEF (P<0.001) and the development of pulmonary remodeling, as compared to controls during a 10-week follow-up. Myocardial strain, as a measure for local cardiac function, decreased in mice with a severe constriction compared to controls (P<0.05). Conclusions Relevant changes in mouse RV and LV function following an aortic constriction could be quantified using MRI. The well-controlled models described here open opportunities to assess the added value of new MRI techniques for the diagnosis of heart failure and to study the impact of new therapeutic strategies on disease progression and symptom occurrence.
Validation of Patient Reported Outcomes Measurement Information System (PROMIS) Computer Adaptive Tests (CATs) in the Surgical Treatment of Lumbar Spinal Stenosis

Study Design. Prospective, cohort study. Objective. Demonstrate validity of Patient reported outcomes measurement information system (PROMIS) physical function, pain interference, and pain behavior computer adaptive tests (CATs) in surgically treated lumbar stenosis patients. Summary of Background Data. There has been increasing attention given to patient reported outcomes associated with spinal interventions. Historical patient outcome measures have inadequate validation, demonstrate floor/ceiling effects, and infrequently used due to time constraints. PROMIS is an adaptive, responsive National Institutes of Health (NIH) assessment tool that measures patient-reported health status. Methods. Ninety-eight consecutive patients were surgically treated for lumbar spinal stenosis and were assessed using PROMIS CATs, Oswestry disability index (ODI), Zurich Claudication Questionnaire (ZCQ), and Short-Form 12 (SF-12). Prior lumbar surgery, history of scoliosis, cancer, trauma, or infection were excluded. Completion time, preoperative assessment, 6 weeks and 3 months postoperative scores were collected. Results. At baseline, 49%, 79%, and 81% of patients had PROMIS pain behavior (PB), pain interference (PI), and physical function (PF) scores greater than 1 standard deviation (SD) worse than the general population. 50.6% were categorized as severely disabled, crippled, or bed bound by ODI. PROMIS CATs demonstrated convergent validity through moderate to high correlations with legacy measures (r = 0.35–0.73). PROMIS CATs demonstrated known groups validity when stratified by ODI levels of disability. ODI improvements of at least 10 points on average had changes in PROMIS scores in the expected direction (PI = −12.98, PB = −9.74, PF = 7.53). PROMIS CATs demonstrated comparable responsiveness to change when evaluated against legacy measures. PROMIS PB and PI decreased 6.66 and 9.62 and PROMIS PF increased 6.8 points between baseline and 3-months post-op (P < 0.001). Completion time for the PROMIS CATs (2.6 min) compares favorably to ODI, ZCQ, and SF-12 scores (3.1, 3.6, and 3.0 min). Conclusion. PROMIS CATs demonstrate convergent validity, known groups validity, and responsiveness for surgically treated patients with lumbar stenosis to detect change over time and are more efficient than legacy instruments. Level of Evidence: 2
Ultrastructural Alterations of Midgut Epithelium, But Not Greater Wing Fluctuating Asymmetry, in Paper Wasps (Polistes dominula) from Urban Environments

Abstract Polistes paper wasps can be used to monitor trace metal contaminants, but the effects of pollution on the health of these insects are still unknown. We evaluated, in a south-eastern area of Spain, whether workers of Polistes dominula collected at urban and rural sites differ in health of midgut tissue and in fluctuating asymmetry, an estimate of developmental noise. We found that wasps collected at the urban sites had abundant lead (Pb)-containing spherites, which were less visible in wasps from the rural sites. Evident ultrastructural alterations in the epithelium of the midgut of the wasps collected at the urban sites included broken and disorganized microvilli, a high amount and density of heterochromatin in the nucleus of epithelial cells, cytoplasmic vacuolization and mitochondrial disruptions. Altogether, these findings suggest a negative effect on the transmembrane transport and a less efficient transcription. On the contrary, a healthy epithelium was observed in wasps from the rural sites. These differences may be preliminarily linked with levels of lead pollution, given that wasps from urban sites had double the Pb concentrations of wasps from rural sites. Level of fluctuating asymmetry was unrelated to wasp origin, thus suggesting no link between developmental noise and Pb-driven pollution.
Performing mathematics activities with non-standard units of measurement using robots controlled via speech-generating devices: three case studies

Abstract Purpose To examine how using a Lego robot controlled via a speech-generating device (SGD) can contribute to how students with physical and communication impairments perform hands-on and communicative mathematics measurement activities. This study was a follow-up to a previous study. Method Three students with cerebral palsy used the robot to measure objects using non-standard units, such as straws, and then compared and ordered the objects using the resulting measurement. Their performance was assessed, and the manipulation and communication events were observed. Teachers and education assistants were interviewed regarding robot use. Results Similar benefits to the previous study were found in this study. Gaps in student procedural knowledge were identified such as knowing to place measurement units tip-to-tip, and students’ reporting revealed gaps in conceptual understanding. However, performance improved with repeated practice. Stakeholders identified that some robot tasks took too long or were too difficult to perform. Conclusions Having access to both their SGD and a robot gave the students multiple ways to show their understanding of the measurement concepts. Though they could participate actively in the new mathematics activities, robot use is most appropriate in short tasks requiring reasonable operational skill. Implications for Rehabilitation Lego robots controlled via speech-generating devices (SGDs) can help students to engage in the mathematics pedagogy of performing hands-on activities while communicating about concepts. Students can “show what they know” using the Lego robots, and report and reflect on concepts using the SGD. Level 1 and Level 2 mathematics measurement activities have been adapted to be accomplished by the Lego robot. Other activities can likely be accomplished with similar robot adaptations (e.g., gripper, pen). It is not recommended to use the robot to measure items that are long, or perform measurements that require high operational competence in order to be successful.
Adhesion of metal brackets to glassy matrix and hybrid CAD/CAM materials after different physico-chemical surface conditioning

Abstract This study compared the adhesion of metal brackets bonded to different CAD/CAM materials after various surface conditioning methods. CAD/CAM blocks (N = 204, n = 17 per group) of (a) VITA Mark II (VM), (b) IPS e.max CAD (IP), (c) Lava Ultimate (LU), and (d) VITA ENAMIC (VE) were conditioned with one of the following methods: C-Control: (fine diamond bur); CJ: (fine diamond bur + air-abrasion with 30 μm SiO2 + silane), and HF: (fine diamond bur +9.5% hydrofluoric acid + silane). Metal brackets were bonded to the conditioned surfaces of the specimens, stored in artificial saliva for 24 h at 37 °C and thermocycled (×1000). Subsequently, the brackets were debonded under shear in a Universal Testing Machine (1 mm/min). Failure types were analyzed under scanning electron microscope. Data were analyzed using two-way ANOVA and Tukey’s tests (α = 0.05). Two-parameter Weibull distribution values, including the Weibull modulus, scale, and shape, were calculated. Mean bond strength (MPa) values were significantly affected by the surface conditioning method (p < 0.001) but not the CAD/CAM material type (p = 0.052). Bond strengths for all CJ and HF-conditioned specimens were twofold higher (11.83 ± 1.95 − 9.44 ± 1.63) than those for control specimens with all materials (4.73 ± 0.93 − 6.02 ± 0.69). Lower mean values were obtained in LU-CJ (9.78 ± 1.61) and LU-HF (9.44 ± 1.63) than those for other groups (11.83 ± 1.95 − 10.93 ± 1.33) groups (p < 0.05). Weibull distribution showed higher shape values for VM-CJ (11.26) and VM-HF (8.87) than those for other groups (0.82–1.83). In control groups, exclusively adhesive and after conditioning mainly mixed failures were observed. Chairside silica coating or HF conditioning significantly improved metal bracket adhesion to both glassy matrix and hybrid CAD/CAM materials tested, with the most reliable adhesion being observed for feldspathic ceramic.
Mathematical Modelling of Nitric Oxide/Cyclic GMP/Cyclic AMP Signalling in Platelets

Platelet activation contributes to normal haemostasis but also to pathologic conditions like stroke and cardiac infarction. Signalling by cGMP and cAMP inhibit platelet activation and are therefore attractive targets for thrombosis prevention. However, extensive cross-talk between the cGMP and cAMP signalling pathways in multiple tissues complicates the selective targeting of their activities. We have used mathematical modelling based on experimental data from the literature to quantify the steady state behaviour of nitric oxide (NO)/cGMP/cAMP signalling in platelets. The analysis provides an assessment of NO-induced cGMP synthesis and PKG activation as well as cGMP-mediated cAMP and PKA activation though modulation of phosphodiesterase (PDE2 and 3) activities. Both one- and two-compartment models of platelet cyclic nucleotide signalling are presented. The models provide new insight for understanding how NO signalling to cGMP and indirectly cAMP, can inhibit platelet shape-change, the initial step of platelet activation. Only the two-compartment models could account for the experimental observation that NO-mediated PKA activation can occur when the bulk platelet cAMP level is unchanged. The models revealed also a potential for hierarchical interplay between the different platelet phosphodiesterases. Specifically, the models predict, unexpectedly, a strong effect of pharmacological inhibitors of cGMP-specific PDE5 on the cGMP/cAMP cross-talk. This may explain the successful use of weak PDE5-inhibitors, such as dipyridamole, in anti-platelet therapy. In conclusion, increased NO signalling or PDE5 inhibition are attractive ways of increasing cGMP-cAMP cross-talk selectively in platelets.
Long-Term Impacts of Forest Ditching on Non-Aquatic Biodiversity: Conservation Perspectives for a Novel Ecosystem

Artificial drainage (ditching) is widely used to increase timber yield in northern forests. When the drainage systems are maintained, their environmental impacts are likely to accumulate over time and along accompanying management, notably after logging when new forest develops on decayed peat. Our study provides the first comprehensive documentation of long-term ditching impacts on terrestrial and arboreal biodiversity by comparing natural alder swamps and second-generation drained forests that have evolved from such swamps in Estonia. We explored species composition of four potentially drainage-sensitive taxonomic groups (vascular plants, bryophytes, lichens, and snails), abundance of species of conservation concern, and their relationships with stand structure in two-ha plots representing four management types (ranging from old growth to clearcut). We found that drainage affected plot-scale species richness only weakly but it profoundly changed assemblage composition. Bryophytes and lichens were the taxonomic groups that were most sensitive both to drainage and timber-harvesting; in closed stands they responded to changed microhabitat structure, notably impoverished tree diversity and dead-wood supply. As a result, natural old-growth plots were the most species-rich and hosted several specific species of conservation concern. Because the most influential structural changes are slow, drainage impacts may be long hidden. The results also indicated that even very old drained stands do not provide quality habitats for old-growth species of drier forest types. However, drained forests hosted many threatened species that were less site type specific, including early-successional vascular plants and snails on clearcuts and retention cuts, and bryophytes and lichens of successional and old forests. We conclude that three types of specific science-based management tools are needed to mitigate ditching effects on forest biodiversity: (i) silvicultural techniques to maintain stand structural complexity; (ii) context-dependent spatial analysis and planning of drained landscapes; and (iii) lists of focal species to monitor and guide ditching practices.
Prolonged Internal Displacement and Common Mental Disorders in Sri Lanka: The COMRAID Study

Background Evidence is lacking on the mental health issues of internally displaced persons, particularly where displacement is prolonged. The COMRAID study was carried out in year 2011 as a comprehensive evaluation of Muslims in North-Western Sri Lanka who had been displaced since 1990 due to conflict, to investigate the prevalence and correlates of common mental disorders. Methods A cross-sectional survey was carried out among a randomly selected sample of internally displaced people who had migrated within last 20 years or were born in displacement. The total sample consisted of 450 adults aged 18–65 years selected from 141 settlements. Common mental disorders (CMDs) and post-traumatic stress disorder (PTSD) prevalences were measured using the Patient Health Questionnaire and CIDI sub-scale respectively. Results The prevalence of any CMD was 18.8%, and prevalence for subtypes was as follows: somatoform disorder 14.0%, anxiety disorder 1.3%, major depression 5.1%, other depressive syndromes 7.3%. PTSD prevalence was 2.4%. The following factors were significantly associated with CMDs: unemployment (odds ratio 2.8, 95% confidence interval 1.6–4.9), widowed or divorced status (4.9, 2.3–10.1) and food insecurity (1.7, 1.0–2.9). Conclusions This is the first study investigating the mental health impact of prolonged forced displacement in post-conflict Sri Lanka. Findings add new insight in to mental health issues faced by internally displaced persons in Sri Lanka and globally, highlighting the need to explore broader mental health issues of vulnerable populations affected by forced displacement.
Sexual and Natural Selection Both Influence Male Genital Evolution

Rapid and divergent evolution of male genital morphology is a conspicuous and general pattern across internally fertilizing animals. Rapid genital evolution is thought to be the result of sexual selection, and the role of natural selection in genital evolution remains controversial. However, natural and sexual selection are believed to act antagonistically on male genital form. We conducted an experimental evolution study to investigate the combined effects of natural and sexual selection on the genital-arch lobes of male Drosophila simulans. Replicate populations were forced to evolve under lifetime monogamy (relaxed sexual selection) or lifetime polyandry (elevated sexual selection) and two temperature regimes, 25°C (relaxed natural selection) or 27°C (elevated natural selection) in a fully factorial design. We found that natural and sexual selection plus their interaction caused genital evolution. Natural selection caused some aspects of genital form to evolve away from their sexually selected shape, whereas natural and sexual selection operated in the same direction for other shape components. Additionally, sexual and natural selection tended to favour larger genitals. Thus we find that the underlying selection driving genital evolution is complex, does not only involve sexual selection, and that natural selection and sexual selection do not always act antagonistically.
Characterization of Phase Transitions Occurring in Solution Treated Ti-15Mo during Heating by Thermal Expansion and Electrical Resistance Measurements

Metastable β titanium alloy Ti-15Mo was investigated in this study. In-situ electrical resistance and thermal expansion measurements conducted on solution treated material revealed influence of ongoing phase transitions on measured properties. The monotonicity of the dependence of electrical resistance on temperature changes at 225, 365 and 560 °C The thermal expansion deviates from linearity between 305 and 580 °C.