Miracle-dz/UniFAR-FTUs huggingface dataset:
Memory and plasticity impairment after binge drinking in adolescent rat hippocampus: GluN2A/GluN2B NMDA receptor subunits imbalance through HDAC2

Ethanol (EtOH) induces cognitive impairment through modulation of synaptic plasticity notably in the hippocampus. The cellular mechanism(s) of these EtOH effects may range from synaptic signaling modulation to alterations of the epigenome. Previously, we reported that two binge‐like exposures to EtOH (3 g/kg, ip, 9 h apart) in adolescent rats abolished long‐term synaptic depression (LTD) in hippocampus slices, induced learning deficits, and increased N‐methyl‐d‐aspartate (NMDA) receptor signaling through its GluN2B subunit after 48 hours. Here, we tested the hypothesis of EtOH‐induced epigenetic alterations leading to modulation of GluN2B and GluN2A NMDA receptor subunits. Forty‐two days old rats were treated with EtOH or the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB, 600 mg/kg, ip) injected alone or 30 minutes before EtOH. After 48 hours, learning was tested with novel object recognition while synaptic plasticity and the role of GluN2A and GluN2B subunits in NMDA‐fEPSP were measured in CA1 field of hippocampus slices. LTD and memory were impaired 48 hours after EtOH and NMDA‐fEPSP analysis unraveled changes in the GluN2A/GluN2B balance. These results were associated with an increase in histone deacetylase (HDAC) activity and HDAC2 mRNA and protein while Ac‐H4K12 labelling was decreased. EtOH increases expression of HDAC2 and mRNA level for GluN2B subunit (but not GluN2A), while HDAC2 modulates the promoter of the gene encoding GluN2B. Interestingly, NaB pretreatment prevented all the cellular and memory‐impairing effects of EtOH. In conclusion, the memory‐impairing effects of two binge‐like EtOH exposure involve NMDA receptor‐dependent LTD deficits due to a GluN2A/GluN2B imbalance resulting from changes in GluN2B expression induced by HDAC2.
ADP-ribosylation of human defensin HNP-1 results in the replacement of the modified arginine with the noncoded amino acid ornithine

Defensins (e.g., human neutrophil peptides, or HNPs) contribute to innate immunity through diverse actions, including microbial killing; high concentrations are present in the lung in response to inflammation. Arginines are critical for HNP activity, which is decreased by their replacement with ornithine. ADP-ribosyltransferases (ARTs) catalyze transfer of ADP-ribose from NAD to an acceptor arginine in a protein substrate, whereas ADP-ribosylarginine hydrolases release ADP-ribose. ART1 on the surface of airway epithelial cells ADP-ribosylated HNP-1 specifically on arginines 14 and 24, with ADP-ribosylation altering biological activity. Di- and mono-ADP-ribosylated HNP-1 were isolated from bronchoalveolar lavage fluid (BALF) of patients with asthma and idiopathic pulmonary fibrosis (IPF), suggesting a role for ADP-ribosylation in disease. In the present study, we observed that ART1-catalyzed ADP-ribosylation of HNP-1 in vitro generated a product with ADP-ribose on arginine 24, and ornithine replacing arginine at position 14. We hypothesized that ADP-ribosylarginine is susceptible to a nonenzymatic hydrolytic reaction yielding ornithine. On incubation of di- or mono-ADP-ribosyl-HNP-1 at 37 °C, ADP-ribosylarginine was partially replaced by ornithine, whereas ornithine was not detected by amino acid analysis and mass spectrometry of unmodified HNP-1 incubated under the same conditions. Further, ornithine was produced from the model compound, ADP-ribosylarginine. BALF from an IPF patient contained ADP-ribosyl-HNP-ornithine as well as mono- and di-ADP-ribosylated HNP-1, consistent with in vivo conversion of arginine to ornithine. Targeted ADP-ribosylation of specific arginines by transferases, resulting in their replacement with ornithine, is an alternative pathway for regulation of protein function through posttranslational modification.
Temporal entrainment in overlapped speech: Cross-linguistic study

In a previous paper we investigated how onsets of overlapped speech in English are timed with respect to syllable boundaries of the current speaker [1]. Overlap initiations were found to be more frequent around syllable boundaries than at other locations within the syllable. In this paper we extend the previous analysis by reporting on results from two other corpora in two different languages (French and German). We found similar trends in all three datasets with an increased likelihood of an overlap initiation shortly before vowel onsets in the interlocutor’s speech.
A framework for cascade size calculations on random networks

We present a framework to calculate the cascade size evolution for a large class of cascade models on random network ensembles in the limit of infinite network size. Our method is exact and applies to network ensembles with almost arbitrary degree distribution, degree-degree correlations, and, in case of threshold models, for arbitrary threshold distribution. With our approach, we shift the perspective from the known branching process approximations to the iterative update of suitable probability distributions. Such distributions are key to capture cascade dynamics that involve possibly continuous quantities and that depend on the cascade history, e.g., if load is accumulated over time. As a proof of concept, we provide two examples: (a) Constant load models that cover many of the analytically tractable casacade models, and, as a highlight, (b) a fiber bundle model that was not tractable by branching process approximations before. Our derivations cover the whole cascade dynamics, not only their steady state. This allows us to include interventions in time or further model complexity in the analysis.
FREQUENCY OF DEPRESSION AND ANXIETY SYMPTOMS IN MEXICAN PATIENTS WITH RHEUMATIC DISEASES DETERMINED BY SELF-ADMINISTERED QUESTIONNAIRES ADAPTED TO THE SPANISH LANGUAGE.

Background The frequency of depression and anxiety symptoms in Spanish-speaking patients suffering from rheumatic conditions is unknown when using self-administered detection tools. Methods A single-center, cross-sectional survey including 413 patients (341 women) with well-defined rheumatic diseases was conducted. The patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder (GAD)-7 questionnaires were used to detect depression and anxiety symptoms, respectively. Results A total of 193 patients (46.7%) reported depression symptoms, and increased PHQ-9 scores were more frequently observed in women than in men (23% vs. 13%; p = 0.038), particularly in association with osteoarthritis, fibromyalgia, Sjögren's syndrome, and osteoporosis. From 88 patients (21.3%) with PHQ-9 scores ≥ 10 points (moderate-to-severe depression symptoms), 27 (30.6%) were previously diagnosed to have depression and only four were under antidepressant treatment. Anxiety symptoms were observed in 168 patients (40.6%) and classified as moderate-to-severe by elevated GAD-7 scores in 68 subjects (16.4%). Of them, 12 (17.6%) were previously diagnosed with GAD, but only 4 (5.8%) were under therapy. Conclusions An unexpected and unusually high frequency of undiagnosed depression and anxiety symptoms was found in rheumatic patients. Self-administered screening tools adapted to the Spanish language are useful and may help clinicians to suspect these conditions.
SenseBelt: A Belt-Worn Sensor to Support Cross-Device Interaction

Mobile interaction is shifting from a single device to simultaneous interaction with ensembles of devices such as phones, tablets, or watches. Spatially-aware cross-device interaction between mobile devices typically requires a fixed tracking infrastructure, which limits mobility. In this paper, we present SenseBelt -- a sensing belt that enhances existing mobile interactions and enables low-cost, ad hoc sensing of cross-device gestures and interactions. SenseBelt enables proxemic interactions between people and their personal devices. SenseBelt also supports cross-device interaction between personal devices and stationary devices, such as public displays. We discuss the design and implementation of SenseBelt together with possible applications. With an initial evaluation, we provide insights into the benefits and drawbacks of a belt-worn mediating sensor to support cross-device interactions.
Unsupervised speaker segmentation of broadcast news using MDL-based Gaussian model

This paper proposes an approach for unsupervised speaker segmentation and gender discrimination of broadcast news. In this paradigm, a speaker segmentation mechanism using MDL-based Gaussian model is firstly adopted to determine the speaker changes using mean and covariance of the Gaussian model. These speaker segments partitioned by speaker changes are smoothed and discriminated into male or female. Experimental results show the proposed method achieved a better performance with 9.2% missed detection rate and 7.5% false alarm rate compared to the Delta-BIC method for speaker segmentation on broadcast news. In addition, the segment-based gender discrimination improves 9% accuracy compared to the clip-based discriminator.
Prospective molecular mechanism of COL5A1 in breast cancer based on a microarray, RNA sequencing and immunohistochemistry

Breast cancer (BC) has a complex etiology and pathogenesis, and is the most common malignant tumor type in females, in USA in 2018, yet its relevant molecular mechanisms remain largely unknown. The collagen type V α-1 chain (COL5A1) gene is differentially expressed in renal and ovarian cancer. Using bioinformatics methods, COL5A1 was determined to also be a significant gene in BC, but its association with BC has not been sufficiently reported. COL5A1 microarray and relevant clinical data were collected from the Gene Expression Omnibus, The Cancer Genome Atlas and other databases to summarize COL5A1 expression in BC and its subtypes at the mRNA and protein levels. All associated information was comprehensively analyzed by various software. The clinical significance of the mutation was obtained via the cBioPortal. Furthermore, Gene Ontology functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were also performed to investigate the mechanism of COL5A1 in BC. Immunohistochemistry was also conducted to detect and confirm COL5A1 expression. It was determined that COL5A1 was highly expressed in BC tissues, compared with normal tissues at the mRNA level [standard mean difference, 0.84; 95% confidence interval (CI), 0.60-1.07; P=0.108]. The area under the summary receiver operator characteristic curve for COL5A1 was 0.87 (95% CI, 0.84-0.90). COL5A1 expression was altered in 32/817 (4%) sequenced samples. KEGG analysis confirmed the most notable pathways, including focal adhesion, extracellular matrix-receptor interaction and regulation of the actin cytoskeleton. Immunohistochemical detection was used to verify the expression of COL5A1 in 136 selected cases of invasive BC tissues and 55 cases of adjacent normal tissues, while the rate of high expression of COL5A1 in BC was up to 90.4%. These results indicated that COL5A1 is highly expressed at the mRNA and protein levels in BC, and the prognosis of patients with BC with high COL5A1 expression may be reduced; therefore, COL5A1 may be used independently or combined with other detection factors in BC diagnosis.
Anle138b Partly Ameliorates Motor Deficits Despite Failure of Neuroprotection in a Model of Advanced Multiple System Atrophy

The neurodegenerative disorder multiple system atrophy (MSA) is characterized by autonomic failure, cerebellar ataxia and parkinsonism in any combination associated with predominantly oligodendroglial α-synuclein (α-syn) aggregates (glial cytoplasmic inclusions = GCIs). To date, there is no effective disease modifying therapy. Previous experiments have shown that the aggregation inhibitor anle138b reduces neurodegeneration, as well as behavioral deficits in both transgenic and toxin mouse models of Parkinson's disease (PD). Here we analyzed whether anle138b improves motor skills and reduces neuronal loss, as well as oligodendroglial α-syn aggregation in the PLP-α-syn transgenic mouse challenged with the mitochondrial toxin 3-nitropropionic acid (3-NP) to model full-blown MSA. Following 1 month of treatment with anle138b, MSA mice showed signs of motor improvement affecting stride length, but not pole, grip strength, and beam test performance. Loss of dopaminergic nigral neurons and Purkinje cells was not attenuated and GCI density remained unchanged. These data suggest that the pathology in transgenic PLP-α-syn mice receiving 3-NP might be too advanced to detect significant effects of anle138b treatment on neuronal loss and intracytoplasmic α-syn inclusion bodies. However, the partial motor amelioration may indicate potential efficacy of anle138b treatment that may be mediated by its actions on α-syn oligomers or may reflect improvement of neuronal dysfunction in neural at risk populations. Further studies are required to address the efficacy of anle138b in transgenic α-syn models of early-stage MSA and in the absence of additional toxin application.
Aniseikonia: A 21st Century Look

ABSTRACT Purpose: Aniseikonia, an appreciation of image size differences between the eyes, can produce symptoms in patients, ranging from headaches to loss of fusion. The purpose of this research was to take a 21st century look at aniseikonia. Methods: Kellogg Eye Center patient records were evaluated for measurable aniseikonia in patients tested with the Aniseikonia Helper, a tablet-based application. Anaglyph slides for the synoptophore were developed to test the limits of induced aniseikonia on stereopsis and fusion. A survey was developed to determine how frequently members of the American Association of Certified Orthoptists (AACO) examine and treat patients with aniseikonia.Results: The prevalence of measurable aniseikonia in this cohort was 7.8%. Moderate amounts of induced aniseikonia, 4% induced image size disparity, disrupt fusion and can cause a loss of stereopsis. Eighty percent of responding AACO members see patients with aniseikonia and among those, 25% see them on a monthly basis. Treatment options, other than wearing contact lenses, are limited to occlusion or fogging techniques. Conclusions: Aniseikonia remains a frequent complaint among patients. The ophthalmologic community needs to use the best methods for measuring aniseikonia and to develop better methods for treating aniseikonia.
Accelerated search of human activity registered by non-invasive sensors

In this paper we present a new approach for accelerated search of human activity registered by noninvasive sensors. A standard data representation in three combined directions x, y and z for the feature vectors are used as input. A k-NN (k-Nearest Neighbors) classifier is trained with the full 3D descriptors. The aim is to recognize one of the following actions — running, walking, going upstairs and down-stairs, sitting, and standing up in a less execution time at the test stage. There a search for particular action could be implemented over a record of prolonged time, e.g. on a daily basis, for an observed person. Following the initial normalization procedures the test vectors are split into groups by components x, xy, yz and xyz which prove to be representative enough for sequential lookup of some of the actions of interest. The approach is considered perspective for application in medical assistive systems for various types of patients where medical personnel could not be involved in permanent superintendence.
A Wearable, Patient-Adaptive Freezing of Gait Detection System for Biofeedback Cueing in Parkinson's Disease

Freezing of Gait (FoG) is a common motor-related impairment among Parkinson's disease patients, which substantially reduces their quality of life and puts them at risk of falls. These patients benefit from wearable FoG detection systems that provide timely biofeedback cues and hence help them regain control over their gait. Unfortunately, the systems proposed thus far are bulky and obtrusive when worn. The objective of this paper is to demonstrate the first integration of an FoG detection system into a single sensor node. To achieve such an integration, features with low computational load are selected and dedicated hardware is designed that limits area and memory utilization. Classification is achieved with a neural network that is capable of learning in real time and thus allows the system to adapt to a patient during run-time. A small form factor FPGA implements the feature extraction and classification, whereas a custom PCB integrates the system into a single node. The system fits into a 4.5 × 3.5 × 1.5 cm$^3$ housing case, weighs 32 g, and achieves 95.6% sensitivity and 90.2% specificity when adapted to a patient. Biofeedback cues are provided either through auditory or somatosensory means and the system can remain operational for longer than 9 h while providing cues. The proposed system is highly competitive in terms of classification performance and excels with respect to wearability and real-time patient adaptivity.
Nanomedicines for the Delivery of Biologics

A special symposium of the Academy of Pharmaceutical Sciences Nanomedicines Focus Group reviewed the current status of the use of nanomedicines for the delivery of biologics drugs. This meeting was particularly timely with the recent approval of the first siRNA-containing product Onpattro™ (patisiran), which is formulated as a lipid nanoparticle for intravenous infusion, and the increasing interest in the use of nanomedicines for the oral delivery of biologics. The challenges in delivering such molecules were discussed with specific emphasis on the delivery both across and into cells. The latest developments in Molecular Envelope Technology® (Nanomerics Ltd, London, UK), liposomal drug delivery (both from an academic and industrial perspective), opportunities offered by the endocytic pathway, delivery using genetically engineered viral vectors (PsiOxus Technologies Ltd, Abingdon, UK), Transint™ technology (Applied Molecular Transport Inc., South San Francisco, CA, USA), which has the potential to deliver a wide range of macromolecules, and AstraZeneca’s initiatives in mRNA delivery were covered with a focus on their uses in difficult to treat diseases, including cancers. Preclinical data were presented for each of the technologies and where sufficiently advanced, plans for clinical studies as well as early clinical data. The meeting covered the work in progress in this exciting area and highlighted some key technologies to look out for in the future.
A Knowledge Discovery Strategy for Relating Sea Surface Temperatures to Frequencies of Tropical Storms and Generating Predictions of Hurricanes Under 21st-century Global Warming Scenarios

The connections among greenhouse-gas emissions scenarios, global warming, and frequencies of hurricanes or tropical cyclones are among the least understood in climate science but among the most fiercely debated in the context of adaptation decisions or mitigation policies. Here we show that a knowledge discovery strategy, which leverages observations and climate model simulations, offers the promise of developing credible projections of tropical cyclones based on sea surface temperatures (SST) in a warming environment. While this study motivates the development of new methodologies in statistics and data mining, the ability to solve challenging climate science problems with innovative combinations of traditional and state-of-the-art methods is demonstrated. Here we develop new insights, albeit in a proof-of-concept sense, on the relationship between sea surface temperatures and hurricane frequencies, and generate the most likely projections with uncertainty bounds for storm counts in the 21st-century warming environment based in turn on the Intergovernmental Panel on Climate Change Special Report on Emissions Scenarios. Our preliminary insights point to the benefits that can be achieved for climate science and impacts analysis, as well as adaptation and mitigation policies, by a solution strategy that remains tailored to the climate domain and complements physics-based climate model simulations with amore » combination of existing and new computational and data science approaches. « less
Sensitive enantioseparation and determination of isoprenaline in human plasma and pharmaceutical formulations.

A simple, sensitive and fast RPHPLC method was developed and validated for the enantioselective determination of (RS)-isoprenaline (Ipn) in human plasma. The enantiomers were converted to diastereomeric derivatives using s-triazine (cyanuric chloride) based chiral derivatizing reagents. l-isoleucine and l-methionine were introduced as chiral auxiliary in s-triazine and two new monochloro-s-triazine reagents were synthesized. These reagents were characterized and used for synthesis of diastereomeric derivatives of (RS)-Ipn spiked in human plasma. (RS)-Ipn was isolated (purified and characterized) from a commercial pharmaceutical formulation and was used as the standard racemic sample. Structures of the two diastereomeric derivatives were optimized for lowest energy using the Gaussian 09 Rev A. 02 program and hybrid density functional B3LYP with 6-31G* basis set which showed the spatial orientation of hydrophobic groups on stereogenic centers in the diastereomeric derivatives. The results were correlated with the mechanism of separation and elution order. Limit of detection values were found to be 24.6 and 26.8 ng mL-1 for the first and second eluting diastereomeric derivatives, respectively.
Belief attribution despite verbal interference

False-belief (FB) tasks have been widely used to study the ability of individuals to represent the content of their conspecifics' mental states (theory of mind). However, the cognitive processes involved are still poorly understood, and it remains particularly debated whether language and inner speech are necessary for the attribution of beliefs to other agents. We present a completely nonverbal paradigm consisting of silent animated cartoons in five closely related conditions, systematically teasing apart different aspects of scene analysis and allowing the assessment of the attribution of beliefs, goals, and physical causation. In order to test the role of language in belief attribution, we used verbal shadowing as a dual task to inhibit inner speech. Data on 58 healthy adults indicate that verbal interference decreases overall performance, but has no specific effect on belief attribution. Participants remained able to attribute beliefs despite heavy concurrent demands on their verbal abilities. Our results are most consistent with the hypothesis that belief attribution is independent from inner speech.