Miracle-dz/UniFAR-FTUs huggingface dataset:
The Alarm Response in Zebrafish: Innate Fear in a Vertebrate Genetic Model

The alarm response is an antipredator behavior displayed by many fish species and was first described 70 years ago. It is triggered through the olfactory system by substances released from injured skin and is characterized by dramatic, measurable changes in locomotion as well as physiology. We propose that this is an ideal time to revisit this response and to utilize it as an assay for understanding how neural circuits mediate innate fear. A suitable organism for these studies is the zebrafish, a genetic model with a rapidly expanding toolkit for molecular manipulation of the nervous system. Individual neurons mediating the response, ranging from receptor neurons to those in higher brain centers, should first be identified. New tools, specifically transgenic lines that allow spatial and temporal control of neural activity, provide a way to define and test the role of specific neurons, while genetic screens provide a route to identifying individual molecules essential for a normal response. Optical recording, which has proven successful in studies of information processing in the bulb, will provide valuable insights into neural circuitry function during the alarm response. When carried out on mutants, physiological analysis can provide insight into aspects of signal processing that are essential for normal behavior. The alarm response thus provides a paradigm to examine innate fear in a vertebrate system, enabling analysis at multiple levels from genes to the entire neural circuit. Additionally, the context dependency of the response can be utilized to investigate attention and decision making.
Arrival Angular Profile Modeling at Mobile Station for Cellular Systems

Spatial processing techniques such as Adaptive Array Antenna (AAA) and Multi-Input-Multi-Output (MIMO) are being considered for use in the next generation mobile cellular systems. In order to accurately estimate the performance of these spatial processing techniques in wide-band mobile communications, we need a time-spatial path model that can present the delay profile and the spatial arrival angular profiles at the same time. We proposed a physical time-spatial path model as a variant of Clark's scattering model and showed by theory and by computer simulation that the proposed model can well match field measurement results with regard to the arrival angular distribution at the BS and the delay time distribution in urban and suburban areas by setting key parameters to appropriate values. In this paper, we propose an empirical arrival angular profile model at the mobile station (MS). First we derive an arrival angular profile model at the MS based on our proposed physical time-spatial path model. Then we optimize the parameters of the model by using field data measured in suburban and urban areas in Tokyo.
On the Interpretation of Factor Analysis

The importance of the researcher's interpretation of factor analysis is illustrated by means of an example. The results from this example appear to be meaningful and easily interpreted. The example omits any measure of reliability or validity. If a measure of reliability had been included, it would have indicated the worthlessness of the results. A survey of 46 recent papers from 6 journals supported the claim that the example is typical, two-thirds of the papers provide no measure of reliability. In fact, some papers did not even provide sufficient information to allow for replication. To improve the current situation some measure of factor reliability should accompany applied studiesthat utilize factor analysis. Three operational approaches are suggested for obtaining measures of factor reliability: use of split samples, Monte Carlo simulation, and a priori models.
Amyotrophic Lateral Sclerosis-associated Proteins TDP-43 and FUS/TLS Function in a Common Biochemical Complex to Co-regulate HDAC6 mRNA*

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that preferentially targets motor neurons. It was recently found that dominant mutations in two related RNA-binding proteins, TDP-43 (43-kDa TAR DNA-binding domain protein) and FUS/TLS (fused in sarcoma/translated in liposarcoma) cause a subset of ALS. The convergent ALS phenotypes associated with TDP-43 and FUS/TLS mutations are suggestive of a functional relationship; however, whether or not TDP-43 and FUS/TLS operate in common biochemical pathways is not known. Here we show that TDP-43 and FUS/TLS directly interact to form a complex at endogenous expression levels in mammalian cells. Binding was mediated by an unstructured TDP-43 C-terminal domain and occurred within the context of a 300–400-kDa complex that also contained C-terminal cleavage products of TDP-43 linked to neuropathology. TDP-43 C-terminal fragments were excluded from large molecular mass TDP-43 ribonucleoprotein complexes but retained FUS/TLS binding activity. The functional significance of TDP-43-FUS/TLS complexes was established by showing that RNAi silencing of either TDP-43 or FUS/TLS reduced the expression of histone deacetylase (HDAC) 6 mRNA. TDP-43 and FUS/TLS associated with HDAC6 mRNA in intact cells and in vitro, and competition experiments suggested that the proteins occupy overlapping binding sites. The combined findings demonstrate that TDP-43 and FUS/TLS form a functional complex in intact cells and suggest that convergent ALS phenotypes associated with TDP-43 and FUS/TLS mutations may reflect their participation in common biochemical processes.
Repurposing Germline Exomes of the Cancer Genome Atlas Demands a Cautious Approach and Sample-Specific Variant Filtering

When seeking to reproduce results derived from whole-exome or genome sequencing data that could advance precision medicine, the time and expense required to produce a patient cohort make data repurposing an attractive option. The first step in repurposing is setting some quality baseline for the data so that conclusions are not spurious. This is difficult because there can be variations in quality from center to center, clinic to clinic and even patient to patient. Here, we assessed the quality of the whole-exome germline mutations of TCGA cancer patients using patterns of nucleotide substitution and negative selection against impactful mutations. We estimated the fraction of false positive variant calls for each exome with respect to two gold standard germline exomes, and found large variability in the quality of SNV calls between samples, cancer subtypes, and institutions. We then demonstrated how variant features, such as the average base quality for reads supporting an allele, can be used to identify sample-specific filtering parameters to optimize the removal of false positive calls. We concluded that while these germlines have many potential applications to precision medicine, users should assess the quality of the available exome data prior to use and perform additional filtering steps.
Yeast as a drug discovery platform in Huntington's and Parkinson's diseases

The high degree of conservation of cellular and molecular processes between the budding yeast Saccharomyces cerevisiae and higher eukaryotes have made it a valuable system for numerous studies of the basic mechanisms behind devastating illnesses such as cancer, infectious disease, and neurodegenerative disorders. Several studies in yeast have already contributed to our basic understanding of cellular dysfunction in both Huntington's and Parkinson's disease. Functional genomics approaches currently being undertaken in yeast may lead to novel insights into the genes and pathways that modulate neuronal cell dysfunction and death in these diseases. In addition, the budding yeast constitutes a valuable system for identification of new drug targets, both via target‐based and non‐target‐based drug screening. Importantly, yeast can be used as a cellular platform to analyze the cellular effects of candidate compounds, which is critical for the development of effective therapeutics. While the molecular mechanisms that underlie neurodegeneration will ultimately have to be tested in neuronal and animal models, there are several distinct advantages to using simple model organisms to elucidate fundamental aspects of protein aggregation, amyloid toxicity, and cellular dysfunction. Here, we review recent studies that have shown that amyloid formation by disease‐causing proteins and many of the resulting cellular deficits can be faithfully recapitulated in yeast. In addition, we discuss new yeast‐based techniques for screening candidate therapeutic compounds for Huntington's and Parkinson's diseases.
A hemophilia A mouse model for the in vivo assessment of Emicizumab function.

The bispecific antibody Emicizumab is increasingly used for hemophilia A-treatment. However, its specificity for human factors IX and X (FIX, FX) has limited its in vivo functional analysis to primate models of acquired hemophilia. Here we describe a novel mouse model allowing to examine Emicizumab function. Briefly, FVIII-deficient mice receive Emicizumab intravenously 24h before performing a tail clip-bleeding model. A second infusion with human FIX and FX is administered 5 min before bleeding. This approach generates consistent levels of Emicizumab (0.7-19 mg/dL for 0.5-10 mg/kg dose) and of both FIX and FX (85 and 101 U/dL respectively, after dosing 100 U/kg). Plasmas from these mice display FVIII-like activity in a diluted aPTT and in thrombin generation assays, similar to human samples containing Emicizumab. Emicizumab doses of 1.5 mg/kg and higher significantly reduced blood loss in a tail clip-bleeding model using FVIII-deficient mice. However, reduction was incomplete compared to mice treated with human FVIII concentrate, and no difference in efficacy between doses was observed. From this model, we deducted a FVIII-like activity of Emicizumab that corresponds to a dose of 4.5 U FVIII/kg (i.e. 9.0 U/dL). Interestingly, combined with a low FVIII dose (5 U/kg), Emicizumab provided additive activity to allow a complete bleeding arrest. This model could be useful for further in vivo analysis of Emicizumab.
Proteolytic enhancement of rotavirus infectivity: molecular mechanisms

The polypeptide compositions of single-shelled and double-shelled simian rotavirus particles were modified by exposure to proteolytic enzymes. Specifically, a major outer capsid polypeptide (VP3) having a molecular weight of 88,000 in double-shelled particles was cleaved by trypsin to yield two polypeptides, VP5* and VP8* (molecular weights, 60,000 and 28,000, respectively). The cleavage of VP3 by enzymes that enhanced infectivity (trypsin, elastase, and pancreatin) yielded different products compared to those detected when VP3 was cleaved by chymotrypsin, which did not enhance infectivity. The appearance of VP5* was correlated with an enhancement of infectivity. Cleavages of the major internal capsid polypeptide VP2 were also observed. The VP2 cleavage products had molecular weights similar to those of known structural and nonstructural rotavirus polypeptides. We confirmed the precursor-product relationships by comparing the peptide maps of the polypeptides generated by digestions with V-8 protease and chymotrypsin. The remaining rotavirus structural polypeptides, including the outer capsid glycoproteins (VP7 and 7a), were not altered by exposure to pancreatic enzymes. Cleavage of VP3 was not required for virus assembly, and specific cleavage of the polypeptides occurred only on assembled particles. We also discuss the role of cleavage activation in other virus-specific biological functions (e.g., hemagglutination and virulence).
FlaC, a protein of Campylobacter jejuni TGH9011 (ATCC43431) secreted through the flagellar apparatus, binds epithelial cells and influences cell invasion

Type III secretion systems identified in bacterial pathogens of animals and plants transpose effectors and toxins directly into the cytosol of host cells or into the extracellular milieu. Proteins of the type III secretion apparatus are conserved among diverse and distantly related bacteria. Many type III apparatus proteins have homologues in the flagellar export apparatus, supporting the notion that type III secretion systems evolved from the flagellar export apparatus. No type III secretion apparatus genes have been found in the complete genomic sequence of Campylobacter jejuni NCTC11168. In this study, we report the characterization of a protein designated FlaC of C. jejuni TGH9011. FlaC is homologous to the N‐ and C‐terminus of the C. jejuni flagellin proteins, FlaA and FlaB, but lacks the central portion of these proteins. flaC null mutants form a morphologically normal flagellum and are highly motile. In wild‐type C. jejuni cultures, FlaC is found predominantly in the extracellular milieu as a secreted protein. Null mutants of the flagellar basal rod gene (flgF) and hook gene (flgE) do not secrete FlaC, suggesting that a functional flagellar export apparatus is required for FlaC secretion. During C. jejuni infection in vitro, secreted FlaC and purified recombinant FlaC bind to HEp‐2 cells. Invasion of HEp‐2 cells by flaC null mutants was reduced to a level of 14% compared with wild type, suggesting that FlaC plays an important role in cell invasion.
The Effect of Trendelenburg Position, Lactated Ringer’s Solution and 6% Hydroxyethyl Starch Solution on Cardiac Output After Spinal Anesthesia

BACKGROUND: The aim of our study was to evaluate the effects of Trendelenburg position, infusion of 6% hydroxyetyl starch solution or lactated Ringer’s solution on changes in cardiac output (CO) after spinal anesthesia in patients older than 50 yr. METHODS: Seventy patients scheduled for lower extremity orthopedic surgery under spinal anesthesia were allocated randomly to one of the three treatment groups. In the Trendelenburg group, the patients were placed in the Trendelenburg position immediately after the spinal block for 10 min. In the hydroxyethyl starch group and the lactated Ringer’s group, the patients received an infusion of 500 mL of 6% hydroxyethyl starch solution or 1000 mL of lactated Ringer’s solution over 20 min after the spinal block. CO was measured continuously from 15 min before until 30 min after spinal anesthesia using the impedance cardiography method and arterial blood pressure with an automated device. P < 0.05 was considered statistically significant. RESULTS: The differences among treatment groups in CO were not statistically significant. Differences in the CO changes from baseline over time were significant. In the Trendelenburg group, CO did not change while the patient was in the Trendelenburg position. In the hydroxyethyl starch group, CO increased significantly after the block and remained significantly increased until the end of measurements. In the lactated Ringer’s group, CO increased significantly 10 and 20 min after the block but, after stopping the infusion, CO started to decrease. CONCLUSIONS: Our study demonstrated that a decrease in CO after spinal anesthesia is prevented by placing the patient in the Trendelenburg position, or infusion of either lactated Ringer’s solution or 6% hydroxyetyl starch solution. Although the effects of the infusion of the lactated Ringer’s solution are transient, the effects of the infusion of 6% hydroxyethyl starch solution are extended beyond the time the infusion.
Oxidation of naphthenoaromatic and methyl-substituted aromatic compounds by naphthalene 1,2-dioxygenase

Oxidation of acenaphthene, acenaphthylene, and fluorene was examined with recombinant strain Pseudomonas aeruginosa PAO1(pRE695) expressing naphthalene dioxygenase genes cloned from plasmid NAH7. Acenaphthene underwent monooxygenation to 1-acenaphthenol with subsequent conversion to 1-acenaphthenone and cis- and trans-acenaphthene-1,2-diols, while acenaphthylene was dioxygenated to give cis-acenaphthene-1,2-diol. Nonspecific dehydrogenase activities present in the host strain led to the conversion of both of the acenaphthene-1,2-diols to 1,2-acenaphthoquinone. The latter was oxidized spontaneously to naphthalene-1,8-dicarboxylic acid. No aromatic ring dioxygenation products were detected from acenaphthene and acenaphthylene. Mixed monooxygenase and dioxygenase actions of naphthalene dioxygenase on fluorene yielded products of benzylic 9-monooxygenation, aromatic ring dioxygenation, or both. The action of naphthalene dioxygenase on a variety of methyl-substituted aromatic compounds, including 1,2,4-trimethylbenzene and isomers of dimethylnaphthalene, resulted in the formation of benzylic alcohols, i.e., methyl group monooxygenation products, which were subsequently converted to the corresponding carboxylic acids by dehydrogenase(s) in the host strain. Benzylic monooxygenation of methyl groups was strongly predominant over aromatic ring dioxygenation and essentially nonspecific with respect to the substitution pattern of the aromatic substrates. In addition to monooxygenating benzylic methyl and methylene groups, naphthalene dioxygenase behaved as a sulfoxygenase, catalyzing monooxygenation of the sulfur heteroatom of 3-methylbenzothiophene.
Sensing-by-Overlaying: A Practical Implementation of a Multiplayer Mixed-Reality Gaming System by Integrating a Dense Point Cloud and a Real-Time Camera

This paper presents a mixed-reality gaming system architecture with a two-phase spatial information processing model. This model assumes that the physical world consists of mainly stable elements such as buildings, and wide-area physical structures are captured in advance by using a 3D laser range scanner. The captured structure data has exactly the same structure and topology as the physical world. Our system recognizes the physical world at runtime by overlaying this virtual structure data on a runtime monocular camera image at exactly the same position. By adopting this model, it is straightforward to implement image-based lighting for photometric integrity and occlusion handling for geometric integrity, because the overlaid virtual structure provides precise distance metrics and depth information. This model also resolves conflicts involving multiple sensing results obtained by multiple users. This paper shows the results of empirical evaluation experiments using the implemented prototype system.
Activity of the Brassinosteroid Transcription Factors BRASSINAZOLE RESISTANT1 and BRASSINOSTEROID INSENSITIVE1-ETHYL METHANESULFONATE-SUPPRESSOR1/BRASSINAZOLE RESISTANT2 Blocks Developmental Reprogramming in Response to Low Phosphate Availability1[W][OPEN]

Pi deprivation shifts the subcellular distribution of two key brassinosteroid-related transcriptional effectors to trigger shallower root system architecture. Plants feature remarkable developmental plasticity, enabling them to respond to and cope with environmental cues, such as limited availability of phosphate, an essential macronutrient for all organisms. Under this condition, Arabidopsis (Arabidopsis thaliana) roots undergo striking morphological changes, including exhaustion of the primary meristem, impaired unidirectional cell expansion, and elevated density of lateral roots, resulting in shallow root architecture. Here, we show that the activity of two homologous brassinosteroid (BR) transcriptional effectors, BRASSINAZOLE RESISTANT1 (BZR1) and BRASSINOSTEROID INSENSITIVE1-ETHYL METHANESULFONATE-SUPPRESSOR1 (BES1)/BZR2, blocks these responses, consequently maintaining normal root development under low phosphate conditions without impacting phosphate homeostasis. We show that phosphate deprivation shifts the intracellular localization of BES1/BZR2 to yield a lower nucleus-to-cytoplasm ratio, whereas replenishing the phosphate supply reverses this ratio within hours. Phosphate deprivation reduces the expression levels of BR biosynthesis genes and the accumulation of the bioactive BR 28-norcastasterone. In agreement, low and high BR levels sensitize and desensitize root response to this adverse condition, respectively. Hence, we propose that the environmentally controlled developmental switch from deep to shallow root architecture involves reductions in BZR1 and BES1/BZR2 levels in the nucleus, which likely play key roles in plant adaptation to phosphate-deficient environments.
Global finite-time stabilisation of a class of switched nonlinear systems

This paper is concerned with the global finite-time stabilisation problem for a class of switched nonlinear systems under arbitrary switchings. All subsystems of the studied switched system under consideration are in lower triangular form. Based on the adding one power integrator technique, both a class of non-Lipschitz continuous state feedback controllers and a common Lyapunov function are simultaneously constructed such that the closed-loop switched system is global finite-time stable under arbitrary switchings. In the controller design process, a common coordinate transformation of all subsystems is exploited to avoid using individual coordinate transformations for subsystems. Finally, two examples are given to show the effectiveness of the proposed method.
Modifying optical properties of reduced/graphene oxide with controlled ozone and thermal treatment in aqueous suspensions

Graphene possesses a number of advantageous properties, however, does not exhibit optical emission, which limits its use in optoelectronics. Unlike graphene, its functional derivative, graphene oxide (GO) exhibits fluorescence emission throughout the visible. Here, we focus on controlled methods for tuning the optical properties of GO. We introduce ozone treatment of reduced graphene oxide (RGO) in order to controllably transform it from non-emissive graphene-like material into GO with a specific fluorescence emission response. Solution-based treatment of RGO for 5–45 min with ∼1.2 g l−1 ozone/oxygen gas mixture yields a drastic color change, bleaching of the absorption in the visible and the stepwise increase in fluorescence intensity and lifetime. This is attributed to the introduction of oxygen-containing functional groups to RGO graphitic platform as detected by the infrared spectroscopy. A reverse process: controllable quenching of this fluorescence is achieved by the thermal treatment of GO in aqueous suspension up to 90 °C. This methodology allows for the wide range alteration of GO optical properties starting from the dark-colored non-emissive RGO material up to nearly transparent highly ozone-oxidized GO showing substantial fluorescence emission. The size of the GO flakes is concomitantly altered by oxidation-induced scission. Semi-empirical PM3 theoretical calculations on HyperChem models are utilized to explore the origins of optical response from GO. Two models are considered, attributing the induced emission either to the localized states produced by oxygen-containing addends or the islands of graphitic carbon enclosed by such addends. Band gap values calculated from the models are in the agreement with experimentally observed transition peak maxima. The controllable variation of GO optical properties in aqueous suspension by ozone and thermal treatments shown in this work provides a route to tune its optical response for particular optoelectronics or biomedical applications.