Miracle-dz/UniFAR-FTUs huggingface dataset:
Visual Orientation and Directional Selectivity through Thalamic Synchrony

Thalamic neurons respond to visual scenes by generating synchronous spike trains on the timescale of 10–20 ms that are very effective at driving cortical targets. Here we demonstrate that this synchronous activity contains unexpectedly rich information about fundamental properties of visual stimuli. We report that the occurrence of synchronous firing of cat thalamic cells with highly overlapping receptive fields is strongly sensitive to the orientation and the direction of motion of the visual stimulus. We show that this stimulus selectivity is robust, remaining relatively unchanged under different contrasts and temporal frequencies (stimulus velocities). A computational analysis based on an integrate-and-fire model of the direct thalamic input to a layer 4 cortical cell reveals a strong correlation between the degree of thalamic synchrony and the nonlinear relationship between cortical membrane potential and the resultant firing rate. Together, these findings suggest a novel population code in the synchronous firing of neurons in the early visual pathway that could serve as the substrate for establishing cortical representations of the visual scene.
Distributions of HLA-A and -B alleles and haplotypes in the Yi ethnic minority of Yunnan, China: relationship to other populations

ObjectiveTo investigate the distributions of human leukocyte antigen (HLA)-A and -B alleles and HLA-A-B haplotypes in the Yi ethnic minority of the Yunnan Province, situated in southwestern China.MethodsDNA typing for HLA-A and -B loci was performed using the polymerase chain reaction-sequence-based typing (PCR-SBT) method on 114 randomly selected healthy individuals of the Yi population. The allelic frequencies of HLA-A and -B loci were calculated by direct counting and HLA-A-B haplotypes were estimated using the expectation maximization algorithm.ResultsA total of 17 HLA-A and 38 HLA-B alleles were found in the Yi population. The most frequent alleles were A*2402 (32.46%), A*1101 (26.32%), and A*0203 (10.09%) at the HLA-A locus and B*4601 (12.28%), B*1525 (10.09%), B*4001 (8.77%), and B*3802 (7.89%) at the HLA-B locus. The predominant HLA-A-B haplotypes were A*2402-B*1525 (7.86%) and A*0203-B*3802 (5.64%), followed by A*1101-B*4001 (4.69%). Phylogenetic analysis indicates that the Yi population in the Honghe, Yunnan Province of China basically belongs to groups of southeastern Asian origin, but shares some characteristics with northeastern Asian groups.ConclusionThe present study may add to the understanding of HLA polymorphism in the Yi ethnic group that was poorly defined previously, and provide useful information for bone marrow transplantation, anthropological research, and forensic sciences as well as for disease-association studies.
Geochemical signature of rare-metal magmatic fluids exsolved from the Beauvoir granite (Massif Central, France) revealed by LA-ICPMS analysis of primary fluid inclusions

The Beauvoir granite (Limousin, French Massif Central) represents an exceptional case in the European Variscan belt of a peraluminous rare-metal granite crosscutting an early W stockwork. The latter was strongly overprinted by the rare-metal magmatic-hydrothermal fluids derived from the Beauvoir granite, resulting in a massive topazification. This work presents a complete study of primary fluid inclusions hosted in quartz and topaz from the Beauvoir granite and the metasomatized stockwork in order to characterize the geochemical composition of the early magmatic fluids exsolved during the crystallization of this highly evolved rare-metal granite. Microthermometric data show that the earliest fluid (L1) is high temperature (500 to >600°C), saline (17-28 wt.% NaCl eq) and Li-rich (Te 100 m) and interaction with external fluids.
Clinical utility of the mBIAS and NSI validity-10 to detect symptom over-reporting following mild TBI: A multicenter investigation with military service members

ABSTRACT Self-report measures are commonly relied upon in military healthcare environments to assess service members following a mild traumatic brain injury (mTBI). However, such instruments are susceptible to over-reporting and rarely include validity scales. This study evaluated the utility of the mild Brain Injury Atypical Symptoms scale (mBIAS) and the Neurobehavioral Symptom Inventory Validity-10 scale to detect symptom over-reporting. A total of 359 service members with a reported history of mTBI were separated into two symptom reporting groups based on MMPI-2-RF validity scales (i.e., non-over-reporting versus symptom over-reporting). The clinical utility of the mBIAS and Validity-10 as diagnostic indicators and screens of symptom over-reporting were evaluated by calculating sensitivity, specificity, positive test rate, positive predictive power (PPP), and negative predictive power (NPP) values. An mBIAS cut score of ≥10 was optimal as a diagnostic indicator, which resulted in high specificity and PPP; however, sensitivity was low. The utility of the mBIAS as a screening instrument was limited. A Validity-10 cut score of ≥33 was optimal as a diagnostic indicator. This resulted in very high specificity and PPP, but low sensitivity. A Validity-10 cut score of ≥7 was considered optimal as a screener, which resulted in moderate sensitivity, specificity, NPP, but relatively low PPP. Owing to low sensitivity, the current data suggests that both the mBIAS and Validity-10 are insufficient as stand-alone measures of symptom over-reporting. However, Validity-10 scores above the identified cut-off of ≥7should be taken as an indication that further evaluation to rule out symptom over-reporting is necessary.
Bayesian Calibration of a Physiologically Based Pharmacokinetic/Pharmacodynamic Model of Carbaryl Cholinesterase Inhibition

Carbaryl, an N-methyl carbamate (NMC), is a common insecticide that reversibly inhibits neuronal cholinesterase activity. The objective of this work was to use a hierarchical Bayesian approach to estimate the parameters in a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model from experimental measurements of carbaryl in rats. A PBPK/PD model was developed to describe the tissue dosimetry of carbaryl and its metabolites (1-naphthol and “other hydroxylated metabolites”) and subsequently to predict the carbaryl-induced inhibition of cholinesterase activity, in particular in the brain and blood. In support of the model parameterization, kinetic tracer studies were undertaken to determine total radioactive tissue levels of carbaryl and metabolites in rats exposed by oral or intravenous routes at doses ranging from 0.8 to 9.2 mg/kg body weight. Inhibition of cholinesterase activity in blood and brain was also measured from the exposed rats. Markov Chain Monte Carlo (MCMC) calibration of the rat model parameters was implemented using prior information from literature for physiological parameter distributions together with kinetic and inhibition data on carbaryl. The posterior estimates of the parameters displayed at most a twofold deviation from the mean. Monte Carlo simulations of the PBPK/PD model with the posterior distribution estimates predicted a 95% credible interval of tissue doses for carbaryl and 1-naphthol within the range of observed data. Similar prediction results were achieved for cholinesterase inhibition by carbaryl. This initial model will be used to determine the experimental studies that may provide the highest added value for model refinement. The Bayesian PBPK/PD modeling approach developed here will serve as a prototype for developing mechanism-based risk models for the other NMCs.
Characterization of the Aleutian disease virus genome and its intracellular forms

Aleutian disease virus (ADV) of mink is a nondefective parvovirus with a single-stranded DNA genome. We characterized the viral DNA forms found in infected cells prepared by a modified Hirt extraction procedure. Double-stranded DNA molecules corresponding in size to 4.8-kilobase-pair duplex monomers and 9.6-kilobase-pair duplex dimers were identified in agarose gels by blot hybridization to 32P-labeled ADV DNA. A rapidly reannealing ADV duplex monomer was isolated on a preparative scale and physically mapped with a series of restriction endonucleases. The map derived was similar to one derived from double-stranded ADV DNA produced by self-primed synthesis on virion DNA, but differed from restriction endonuclease maps reported for other parvovirus DNAs. The purified duplex monomer could be labeled with [32P]dCTP by nick translation and used as a probe in blot hybridization to detect ADV sequences in DNA from small numbers of infected cells. Additional studies indicated that double-stranded ADV DNA could first be detected at 24 h after infection.
Flattening statecharts without explosions

We present a polynomial upper bound for flattening of UML statecharts. An efficient flattening technique is derived and implemented in SCOPE---a code generator targeting constrained embedded systems. Programs generated with this new technique are both faster and smaller than those produced by non-flattening code generators. Our approach scales well for big models and exhibits good properties with respect to memory usage, automatic analysis of worst-case reaction time and automatic validation of memory safety.
Abberant α-Synuclein Confers Toxicity to Neurons in Part through Inhibition of Chaperone-Mediated Autophagy

Background The mechanisms through which aberrant α-synuclein (ASYN) leads to neuronal death in Parkinson's disease (PD) are uncertain. In isolated liver lysosomes, mutant ASYNs impair Chaperone Mediated Autophagy (CMA), a targeted lysosomal degradation pathway; however, whether this occurs in a cellular context, and whether it mediates ASYN toxicity, is unknown. We have investigated presently the effects of WT or mutant ASYN on the lysosomal pathways of CMA and macroautophagy in neuronal cells and assessed their impact on ASYN-mediated toxicity. Methods and Findings Novel inducible SH-SY5Y and PC12 cell lines expressing human WT and A53T ASYN, as well as two mutant forms that lack the CMA-targeting motif were generated. Such forms were also expressed in primary cortical neurons, using adenoviral transduction. In each case, effects on long-lived protein degradation, LC3 II levels (as a macroautophagy index), and cell death and survival were assessed. In both PC12 and SH-SY5Y cycling cells, induction of A53T ASYN evoked a significant decrease in lysosomal degradation, largely due to CMA impairment. In neuronally differentiated SH-SH5Y cells, both WT and A53T ASYN induction resulted in gradual toxicity, which was partly dependent on CMA impairment and compensatory macroautophagy induction. In primary neurons both WT and A53T ASYN were toxic, but only in the case of A53T ASYN did CMA dysfunction and compensatory macroautophagy induction occur and participate in death. Conclusions Expression of mutant A53T, and, in some cases, WT ASYN in neuronal cells leads to CMA dysfunction, and this in turn leads to compensatory induction of macroautophagy. Inhibition of these lysosomal effects mitigates ASYN toxicity. Therefore, CMA dysfunction mediates aberrant ASYN toxicity, and may be a target for therapeutic intervention in PD and related disorders. Furthermore, macroautophagy induction in the context of ASYN over-expression, in contrast to other settings, appears to be a detrimental response, leading to neuronal death.
Visual Short-Term Memory Load Suppresses Temporo-Parietal Junction Activity and Induces Inattentional Blindness

The right temporo-parietal junction (TPJ) is critical for stimulus-driven attention and visual awareness. Here we show that as the visual short-term memory (VSTM) load of a task increases, activity in this region is increasingly suppressed. Correspondingly, increasing VSTM load impairs the ability of subjects to consciously detect the presence of a novel, unexpected object in the visual field. These results not only demonstrate that VSTM load suppresses TPJ activity and induces inattentional blindness, but also offer a plausible neural mechanism for this perceptual deficit: suppression of the stimulus-driven attentional network.
A robust statistical framework for instantaneous electroencephalogram phase and frequency estimation and analysis

Objective: The instantaneous phase (IP) and instantaneous frequency (IF) of the electroencephalogram (EEG) are considered as notable complements for the EEG spectrum. The calculation of these parameters commonly includes narrow-band filtering, followed by the calculation of the signal’s analytical form. The calculation of the IP and IF is highly susceptible to the filter parameters and background noise level, especially in low analytical signal amplitudes. The objective of this study is to propose a robust statistical framework for EEG IP/IF estimation and analysis. Approach: Herein, a Monte Carlo estimation scheme is proposed for the robust estimation of the EEG IP and IF. It is proposed that any EEG phase-related inference should be reported as an average with confidence intervals obtained by repeating the IP and IF estimation under infinitesimal variations (selected by an expert), in algorithmic parameters such as the filter’s bandwidth, center frequency and background noise level. In the second part of the paper, a stochastic model consisting of the superposition of narrow-band foreground and background EEG is used to derive analytically probability density functions of the instantaneous envelope (IE) and IP of EEG signals, which justify the proposed Monte Carlo scheme. Main results: The instantaneous analytical envelope of the EEG, which has been empirically used in previous studies, is shown to have a fundamental impact on the accuracy of the EEG phase contents. It is rigorously shown that the IP/IF estimation quality highly depends on the IE and any phase/frequency interpretations in low IE are statistically unreliable and require a hypothesis test. Significance: The impact of the proposed method on previous studies, including time-domain phase synchrony, phase resetting, phase locking value and phase amplitude coupling are studied with examples. The findings of this research can set forth new standards for EEG phase/frequency estimation and analysis techniques.
Institutional Repository Two-dimensional uid with competing interactions exhibiting microphase separation : Theory for bulk and interfacial properties

Two-dimensional uid with competing interactions exhibiting microphase separation: Theory for bulk and interfacial properties. Colloidal particles that are confined to an interface such as the air-water interface are an example of a two-dimensional fluid. Such dispersions have been observed to spontaneously form cluster and stripe morphologies in certain systems with isotropic pair potentials between the particles, due to the fact that the pair interaction between the colloids has competing attraction and repulsion over different length scales. Here we present a simple density functional theory for a model of such a two-dimensional fluid. The theory predicts a bulk phase diagram exhibiting cluster, stripe, and bubble modulated phases, in addition to homogeneous fluid phases. Comparing with simulation results for this model from the literature, we find that the theory is qualitatively reliable. The model allows for a detailed investigation of the structure of the fluid and we are able to obtain simple approximate expressions for the static structure factor and for the length scale characterizing the modulations in the microphase separated phases. We also investigate the behavior of the system under confinement between two parallel hard walls. We find that the confined fluid phase behavior can be rather complex.
Ultrasonic verification of five wave fronts in unidirectional graphite epoxy composite. Final Report

The existence of five different waves fronts in a unidirectional graphite fiber reinforced epoxy composite with energy flux propagation at the angle of 60 deg with respect to the fiber direction is verified by measuring their corresponding group and phase velocities of longitudinal and shear waves using the through transmission technique. The experimental and theoretical values of phase velocities show excellent agreement for all three modes of wave propagation. It is also verified that the maximum output voltage amplitude is obtained when the line joining the centers of the transmitting and receiving transducers is parallel to the energy propagation direction defined by the deviation angle.
pHEMA Encapsulated PEDOT-PSS-CNT Microsphere Microelectrodes for Recording Single Unit Activity in the Brain

The long-term reliability of neural interfaces and stability of high-quality recordings are still unsolved issues in neuroscience research. High surface area PEDOT-PSS-CNT composites are able to greatly improve the performance of recording and stimulation for traditional intracortical metal microelectrodes by decreasing their impedance and increasing their charge transfer capability. This enhancement significantly reduces the size of the implantable device though preserving excellent electrical performances. On the other hand, the presence of nanomaterials often rises concerns regarding possible health hazards, especially when considering a clinical application of the devices. For this reason, we decided to explore the problem from a new perspective by designing and testing an innovative device based on nanostructured microspheres grown on a thin tether, integrating PEDOT-PSS-CNT nanocomposites with a soft synthetic permanent biocompatible hydrogel. The pHEMA hydrogel preserves the electrochemical performance and high quality recording ability of PEDOT-PSS-CNT coated devices, reduces the mechanical mismatch between soft brain tissue and stiff devices and also avoids direct contact between the neural tissue and the nanocomposite, by acting as a biocompatible protective barrier against potential nanomaterial detachment. Moreover, the spherical shape of the electrode together with the surface area increase provided by the nanocomposite deposited on it, maximize the electrical contact and may improve recording stability over time. These results have a good potential to contribute to fulfill the grand challenge of obtaining stable neural interfaces for long-term applications.
Stable, solution-processed, high-mobility ZnO thin-film transistors.

A stable, high-mobility ZnO thin-film semiconductor was fabricated by thermal treatment of a solution-deposited thin film from a solution of Zn(OAc)2/2-ethanolamine in methoxyethanol. This ZnO thin-film semiconductor was composed of closely packed ZnO single crystals (∼30 to 50 nm) having a hexagonal structure assuming a preferred orientation with its c-axis perpendicular to the substrate. Field-effect mobility of 5−6 cm2 V-1 s-1 and current on-to-off ratio of 105−106 were demonstrated with this ZnO thin-film semiconductor in thin-film transistors.
Steroid profiles in cultured female jundiá, the Siluridae Rhamdia quelen (Quoy and Gaimard, Pisces Teleostei), during the first reproductive cycle.

The jundiá Rhamdia quelen (Quoy and Gaimard) is a teleost species from the Siluridae family and is an important species for aquaculture in temperate and subtropical climates. Gonad and blood tissue samples were taken from cultured jundiá females between 1998 and 1999. Plasma concentrations of 17beta-estradiol (E(2)), testosterone (T), 11-ketotestosterone (11-KT), 17-hydroxy-4-pregnene-3,20-dione (17-P), 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P), and 17,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S) were measured by radioimmunoassay and potential correlations with the stage of oogenesis and sexual maturation examined. During the experimental period two spawning episodes were observed. Plasma concentrations of E(2) increased progressively during oocyte development, simultaneously with the appearance of yolk vesicles and increasing amounts of deposited yolk. In female jundiá, the T peak occurred in October and was coincident with the peak in gonadosomatic index. Two distinct peaks of progestogens were detected, corresponding to the two spawning episodes, suggesting that one or more of these steroids might act as the "maturational-inducing steroid" in jundiá. Unusually large amounts of 11-KT were also measured in the plasma of mature jundiá females. The identity of 11-KT was confirmed by thin-layer chromatography. Although the profiles of the other steroids are compatible with the roles proposed for the action of these hormones in other teleosts, the role of 11-KT, normally found only in males, is unknown.
Copy Number Variations Burden on miRNA Genes Reveals Layers of Complexities Involved in the Regulation of Pathways and Phenotypic Expression

MicroRNAs are involved in post-transcriptional down-regulation of gene expression. Variations in miRNA genes can severely affect downstream-regulated genes and their pathways. However, population-specific burden of CNVs on miRNA genes and the complexities created towards the phenotype is not known. From a total of 44109 CNVs investigated from 1715 individuals across 12 populations using high-throughput arrays, 4007 miRNA-CNVs (∼9%) consisting 6542 (∼5%) miRNA genes with a total of 333 (∼5%) singleton miRNA genes were identified. We found miRNA-CNVs across the genomes of individuals showing multiple hits in many targets, co-regulated under the same pathway. This study proposes four mechanisms unraveling the many complexities in miRNA genes, targets and co-regulated miRNA genes towards establishment of phenotypic diversity.
Protective Effect of Clove Oil-Supplemented Fish Diets on Experimental Lactococcus garvieae Infection in Tilapia

The essential oils extracted from the four herbs, cinnamon (Cinnamomum verum), clove (Syzygium aromaticum), ginger (Zingiber officinale) and holy basil (Ocimum sanctum), were investigated for their antimicrobial activity and mode of action against Lactococcus garvieae, a fish pathogenic bacteria causing lactococcosis. Of all the tested oils, clove oil had the strongest inhibitory effect and exhibited a bactericidal mode of action against the pathogenic bacterium. When an intraperitoneal infection of tilapia (Oreochromis niloticus) with L. garvieae was performed, the median lethal dose (LD50) was determined to be 1.78×102 CFU/fish. For an in vivo trial, no mortality was apparent in fish fed on the fish diets supplemented with 3% (w/w) of clove oil and with 0.5% (w/w) of oxytetracycline 5 d prior to the infection with L. garvieae. These results indicate that clove oil had a protective effect on experimental L. garvieae infection in tilapia and the potential to replace antibiotics for controlling the disease.
Arabidopsis RETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control

The rapidly proliferating cells in plant meristems must be protected from genome damage. Here, we show that the regulatory role of the Arabidopsis RETINOBLASTOMA RELATED (RBR) in cell proliferation can be separated from a novel function in safeguarding genome integrity. Upon DNA damage, RBR and its binding partner E2FA are recruited to heterochromatic γH2AX‐labelled DNA damage foci in an ATM‐ and ATR‐dependent manner. These γH2AX‐labelled DNA lesions are more dispersedly occupied by the conserved repair protein, AtBRCA1, which can also co‐localise with RBR foci. RBR and AtBRCA1 physically interact in vitro and in planta. Genetic interaction between the RBR‐silenced amiRBR and Atbrca1 mutants suggests that RBR and AtBRCA1 may function together in maintaining genome integrity. Together with E2FA, RBR is directly involved in the transcriptional DNA damage response as well as in the cell death pathway that is independent of SOG1, the plant functional analogue of p53. Thus, plant homologs and analogues of major mammalian tumour suppressor proteins form a regulatory network that coordinates cell proliferation with cell and genome integrity.