Miracle-dz/UniFAR-FTUs huggingface dataset:
A recurrent PAX6 mutation is associated with aniridia and congenital progressive cataract in a Chinese family

Purpose Aniridia is phenotyically and genetically heterogeneous. This study is to summarize the phenotypes and identify the genetic defect responsible for aniridia and congenital progressive cataract in a three generation Chinese family. Methods A detailed family history and clinical data from patients were collected by ophthalmologic examination, including visual acuity, slit-lamp examination, tonometer, keratometry, corneal topography, optical coherence tomography, and ultrasonic A/B scan. All exons and flanking intronic sequences of the paired box 6 (PAX6) gene were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Structure and function of the mutant PAX6 were analyzed by bioinformatics analysis. Results All the six patients shared common manifestations of complete aniridia, congenital cataract and thickened cornea, and broad phenotypic variability was observed in nystagmus, ptosis, strabismus, glaucoma, corneal pannus, corneal curvature, corneal vascularization, cataract subtype, ectopia lentis, axial length, and optic disc anomalies. Sequencing of the candidate gene detected a heterozygous c.307C>T transition in the coding region of PAX6, resulting in the substitution of a highly conserved arginine codon for a termination codon (p.R103X). The p.P103X mutation co-segregated with the affected individuals in the family. The change was supposed to cause structural and functional changes based on computational analysis. Conclusions We identified a recurrent PAX6 c.307C>T mutation in an aniridia and congenital progressive cataract family, and summarized the variable phenotypes among the patients, which expanded the phenotypic spectrum of aniridia in a different ethnic background.
Control of orienting gaze shifts by the tectoreticulospinal system in the head-free cat. III. Spatiotemporal characteristics of phasic motor discharges.

1. In this paper we describe the movement-related discharges of tectoreticular and tectoreticulospinal neurons [together called TR (S) Ns] that were recorded in the superior colliculus (SC) of alert cats trained to generate orienting movements in various behavioral situations; the cats' heads were either completely unrestrained (head free) or immobilized (head fixed). TR (S) Ns are organized into a retinotopically coded motor map. These cells can be divided into two groups, fixation TR (S) Ns [f TR (S) Ns] and orientation TR (S) Ns [oTR(S)Ns], depending on whether they are located, respectively, within or outside the zero (or area centralis) representation of the motor map in the rostral SC. 2. oTR(S)Ns discharged phasic motor bursts immediately before the onset of gaze shifts in both the head-free and head-fixed conditions. Ninety-five percent of the oTR(S)Ns tested (62/65) increased their rate of discharge before a visually triggered gaze shift, the amplitude and direction of which matched the cell's preferred movement vector. For movements along the optimal direction, each cell produced a burst discharge for gaze shifts of all amplitudes equal to or greater than the optimum. Hence, oTR(S)Ns had no distal limit to their movement fields. The timing of the burst relative to the onset of the gaze shift, however, depended on gaze shift amplitude: each TR(S)N reached its peak discharge when the instantaneous position of the visual axis relative to the target (i.e., instantaneous gaze motor error) matched the cell's optimal vector, regardless of the overall amplitude of the movement. 3. The intensity of the movement-related burst discharge depended on the behavioral context. For the same vector, the movement-related increase in firing was greatest for visually triggered movements and less pronounced when the cat oriented to a predicted target, a condition in which only 76% of the cells tested (35/46) increased their discharge rate. The weakest movement-related discharges were associated with spontaneous gaze shifts. 4. For some oTR(S)Ns, the average firing frequency in the movement-related burst was correlated to the peak velocity of the movement trajectory in both head-fixed and head-free conditions. Typically, when the head was unrestrained, the correlation to peak gaze velocity was better than that to either peak eye or head velocity alone. 5. Gaze shifts triggered by a high-frequency train of collicular microstimulation had greater peak velocities than comparable amplitude movements elicited by a low-frequency train of stimulation. (ABSTRACT TRUNCATED AT 400 WORDS)
Is it worth to retransmit lost packets in Networked Control Systems?

Recent publications showed that packet loss significantly reduces the performance of Networked Control Systems (NCS). One approach to increase the reliability of the communication system is to retransmit lost packets. Obviously, such retransmissions take time and thus require to increase the sampling time. Increasing the sampling time generally degrades the performance of a control system. Thus, we raise the question whether it is worth to increase the sampling time to allow more packet transmissions per sampling interval.
Extracting places from traces of locations

Location-aware systems are proliferating on a variety of platforms from laptops to cell phones. Locations are expressed in two principal ways: coordinates and landmarks. However, users are often more interested in "places" rather than locations. A place is a locale that is important to an individual user and carries important semantic meanings such as being a place where one works, lives, plays, meets socially with others, etc. Our devices can make more intelligent decisions on how to behave when they have this higher level information. For example, a cell phone can switch to a silent mode when the user is in a quiet place (e.g., a movie theater, a lecture hall, or a place where one meets socially with others). It would be tedious to define this in terms of coordinates. In this paper, we describe an algorithm for extracting significant places from a trace of coordinates, and evaluate the algorithm with real data collected using Place Lab [14], a coordinate-based location system that uses a database of locations for WiFi hotspots.
Machine Learning-Based Ensemble Prediction of Water-quality Variables Using Feature-level and Decision-level Fusion with Proximal Remote Sensing

The objectives of this study were to accurately model relationships between spectral reflectance and water-quality parameters, including blue-green algae phycocyanin, chlorophyll a, total suspended solids, turbidity, and total dissolved solids; evaluate feature-level fusion to spectral data for water-quality modeling; and evaluate the effectiveness of machine learning regression techniques and decision-level fusion for water-quality variable prediction. We introduce the application of canonical correlation analysis fusion as a method for water-based spectral analysis to overcome the low signal-to-noise ratio of the data. Water-quality variables and spectral reflectance were used to create predictive models via machine learning regression models, including multiple linear regression, partial least-squares regression, Gaussian process regression, support vector machine regression, and extreme learning machine regression. The models were then combined using decision-level fusion. Results indicate that canonical correlation analysis feature-level fusion and machine learning techniques are superior to traditional methods.
Structural evolution of a crustal-scale shear zone through a decreasing temperature regime: The Yukon River shear zone, Yukon-Tanana terrane, Northern Cordillera

We present the first detailed structural analysis of the Yukon River shear zone (YRSZ), which forms an important structural break within the Yukon-Tanana terrane of the Northern Cordillera in Yukon (Canada). The YRSZ is a NW-SE–striking shear zone that juxtaposes Mississippian orthogneiss hanging-wall rocks (Simpson Range suite) against pre-Late Devonian metasedimentary footwall rocks (Snowcap assemblage). Field and microstructural analyses, including quartz c-axis fabric investigation, indicate that the YRSZ initiated as a top-ESE mid-crustal shear zone active through a temperature range of ≥650–500 °C to ~540–440 °C. Constraints from the footwall associated with top-ESE shearing on the YRSZ at mid-crustal conditions record a decrease in deformation temperature toward the shear zone, coincident with a transition from coaxial to non-coaxial deformation and an increase in fabric intensity, strain rate, and differential stress estimates. Collectively, these spatial trends represent a classic example of a narrowing shear zone that progressively localizes and intensifies deformation as ambient temperature decreases. U-Pb zircon geochronometry of a deformed Permian orthogneiss from within the YRSZ combined with previously published thermochronometry bracket the timing of top-ESE mid-crustal shearing between 259 ± 2 Ma and 176–168 Ma, either during Late Permian–Middle Triassic metamorphism and lithospheric extension or latest Triassic–Early Jurassic metamorphism and crustal thickening. The YRSZ was subsequently reactivated as a top-WNW upper-crustal thrust fault zone during or after Early to Middle Jurassic cooling and exhumation at 176–168 Ma. This top-WNW thrusting within the YRSZ may be responsible for structural separation of Late Triassic and Early Jurassic plutonic rocks in the hanging wall of the YRSZ from Permian plutonic rocks in its footwall. LITHOSPHERE; v. 10; no. 6; p. 760–782; GSA Data Repository Item 2018357 | Published online 11 October 2018 https:// doi . org /10 . 1130 /L724 . 1
ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor

Drugs that target specific gene alterations have proven beneficial in the treatment of cancer. Because cancer cells have multiple resistance mechanisms, it is important to understand the downstream pathways of the target genes and monitor the pharmacodynamic markers associated with therapeutic efficacy. We performed a transcriptome analysis to characterize the response of various cancer cell lines to a selective fibroblast growth factor receptor (FGFR) inhibitor (CH5183284/Debio 1347), a mitogen-activated protein kinase kinase (MEK) inhibitor, or a phosphoinositide 3-kinase (PI3K) inhibitor. FGFR and MEK inhibition produced similar expression patterns, and the extracellular signal–regulated kinase (ERK) gene signature was altered in several FGFR inhibitor–sensitive cell lines. Consistent with these findings, CH5183284/Debio 1347 suppressed phospho-ERK in every tested FGFR inhibitor–sensitive cell line. Because the mitogen-activated protein kinase (MAPK) pathway functions downstream of FGFR, we searched for a pharmacodynamic marker of FGFR inhibitor efficacy in a collection of cell lines with the ERK signature and identified dual-specificity phosphatase 6 (DUSP6) as a candidate marker. Although a MEK inhibitor suppressed the MAPK pathway, most FGFR inhibitor–sensitive cell lines are insensitive to MEK inhibitors and we found potent feedback activation of several pathways via FGFR. We therefore suggest that FGFR inhibitors exert their effect by suppressing ERK signaling without feedback activation. In addition, DUSP6 may be a pharmacodynamic marker of FGFR inhibitor efficacy in FGFR-addicted cancers. Mol Cancer Ther; 14(12); 2831–9. ©2015 AACR.
N-Salicyloyltryptamine, an N-Benzoyltryptamine Analogue, Induces Vasorelaxation through Activation of the NO/sGC Pathway and Reduction of Calcium Influx

Benzoyltryptamine analogues act as neuroprotective and spasmolytic agents on smooth muscles. In this study, we investigated the ability of N-salicyloyltryptamine (STP) to produce vasorelaxation and determined its underlying mechanisms of action. Isolated rat mesenteric arteries with and without functional endothelium were studied in an isometric contraction system in the presence or absence of pharmacological inhibitors. Amperometric experiments were used to measure the nitric oxide (NO) levels in CD31+ cells using flow cytometry. GH3 cells were used to measure Ca2+ currents using the whole cell patch clamp technique. STP caused endothelium-dependent and -independent relaxation in mesenteric rings. The endothelial-dependent relaxations in response to STP were markedly reduced by L-NAME (endothelial NO synthase—eNOS—inhibitor), jHydroxocobalamin (NO scavenger, 30 µM) and ODQ (soluble Guanylyl Cyclase—sGC—inhibitor, 10 µM), but were not affected by the inhibition of the formation of vasoactive prostanoids. These results were reinforced by the increased NO levels observed in the amperometric experiments with freshly dispersed CD31+ cells. The endothelium-independent effect appeared to involve the inhibition of voltage-gated Ca2+ channels, due to the inhibition of the concentration-response Ca2+ curves in depolarizing solution, the increased relaxation in rings that were pre-incubated with high extracellular KCl (80 mM), and the inhibition of macroscopic Ca2+ currents. The present findings show that the activation of the NO/sGC/cGMP pathway and the inhibition of gated-voltage Ca2+ channels are the mechanisms underlying the effect of STP on mesenteric arteries.
Seasonal differences in the testicular transcriptome profile of free-living European beavers (Castor fiber L.) determined by the RNA-Seq method

The European beaver (Castor fiber L.) is an important free-living rodent that inhabits Eurasian temperate forests. Beavers are often referred to as ecosystem engineers because they create or change existing habitats, enhance biodiversity and prepare the environment for diverse plant and animal species. Beavers are protected in most European Union countries, but their genomic background remains unknown. In this study, gene expression patterns in beaver testes and the variations in genetic expression in breeding and non-breeding seasons were determined by high-throughput transcriptome sequencing. Paired-end sequencing in the Illumina HiSeq 2000 sequencer produced a total of 373.06 million of high-quality reads. De novo assembly of contigs yielded 130,741 unigenes with an average length of 1,369.3 nt, N50 value of 1,734, and average GC content of 46.51%. A comprehensive analysis of the testicular transcriptome revealed more than 26,000 highly expressed unigenes which exhibited the highest homology with Rattus norvegicus and Ictidomys tridecemlineatus genomes. More than 8,000 highly expressed genes were found to be involved in fundamental biological processes, cellular components or molecular pathways. The study also revealed 42 genes whose regulation differed between breeding and non-breeding seasons. During the non-breeding period, the expression of 37 genes was up-regulated, and the expression of 5 genes was down-regulated relative to the breeding season. The identified genes encode molecules which are involved in signaling transduction, DNA repair, stress responses, inflammatory processes, metabolism and steroidogenesis. Our results pave the way for further research into season-dependent variations in beaver testes.
Time-frequency complexity and information

Many functions have been proposed for estimating signal information content and complexity on the time-frequency plane, including moment-based measures such as the time-bandwidth product and the Shannon and Renyi(see 4th Berkeley Symp. Math., Stat., Prob., vol.1) entropies. When applied to a time-frequency representation from Cohen's (1989) class, the Renyi entropy conforms closely to the visually based notion of complexity that we use when inspecting time-frequency images. A detailed discussion reveals many of the desirable properties of the Renyi information measure for both deterministic and random signals. <<ETX>>
Using complete system simulation to characterize SPECjvm98 benchmarks

Complete system simulation to understand the influence of architecture and operating systems on application execution has been identified to be crucial for systems design. While there have been previous attempts at understanding the architectural impact of Java programs, there has been no prior work investigating the operating system (kernel) activity during their executions. This problem is particularly interesting in the context of Java since it is not only the application that can invoke kernel services, but so does the underlying Java Virtual Machine (JVM) implementation which runs these programs. Further, the JVM style (JIT compiler or interpreter) and the manner in which the different JVM components (such as the garbage collector and class loader) are exercised, can have a significant impact on the kernel activities. To investigate these issues, this research uses complete system simulation of the SPECjvm98 benchmarks on the SimOS simulation platform. The execution of these benchmarks on both JIT compilers and interpreters is profiled in detail, to identify and quantify where time is spent in each component. The kernel activity of SPECjvm98 applications constitutes up to 17% of the execution time in the large dataset and up to 31% in the small dataset. The average kernel activity in the large dataset is approximately 10%, in comparison to around 2% in four SPECInt benchmarks studied. Of the kernel services, TLB miss handling is the most dominant in all applications. The TLB miss rates in the JIT compiler, dynamic class loader and garbage collector portions of the JVM are individually analyzed. In addition to such execution profiles, the ILP in the user and kernel mode are also quantified. The Java code is seen to limit exploitable parallelism and aggressive instruction issue is seen to be less efficient for SPECjvm98 benchmarks in comparison to SPEC95 programs. Also, the kernel mode of execution does not exhibit as much ILP as the user mode.
MOTIFSIM 2.1: An Enhanced Software Platform for Detecting Similarity in Multiple DNA Motif Data Sets

Abstract Finding binding site motifs plays an important role in bioinformatics as it reveals the transcription factors that control the gene expression. The development for motif finders has flourished in the past years with many tools have been introduced to the research community. Although these tools possess exceptional features for detecting motifs, they report different results for an identical data set. Hence, using multiple tools is recommended because motifs reported by several tools are likely biologically significant. However, the results from multiple tools need to be compared for obtaining common significant motifs. MOTIFSIM web tool and command-line tool were developed for this purpose. In this work, we present several technical improvements as well as additional features to further support the motif analysis in our new release MOTIFSIM 2.1.
Pathology and virus dispersion in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus via different inoculation routes

Severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV) causes SARS. The pathogenic mechanisms of SARS‐CoV remain poorly understood. Six cynomolgus monkeys were inoculated with the HKU39849 isolate of SARS‐CoV via four routes. After intranasal inoculation, the virus was isolated from respiratory swabs on days 2–7 postinoculation (p.i.) and virus genome was detected in intestinal tissues on day 7 p.i. Virus was not detected after intragastric inoculation. After intravenous inoculation, infectious virus was isolated from rectal swabs, and virus antigen was detected in intestinal cells on day 14 p.i. After intratracheal (i.t.) inoculation, virus antigen‐positive alveolar cells and macrophages were found in lung and infectious virus was detected in lymphoid and intestinal tissues. The peribronchial lymph nodes showed evidence of an immune response. Lung tissue and/or fluid and/or the peribronchial lymph node of the intratracheally inoculated animals had high TNF‐α, IL‐8 and IL‐12 levels. SARS lung lesions are only generated in monkeys by i.t. inoculation. The virus appears to spread into and perhaps via the intestinal and lymphatic systems. It has been suggested previously that viraemia may cause intestinal infections in SARS patients.
JustModeling: An MDE Approach to Develop Android Business Applications

The continuous growth of the Android market has resulted in greater demand for applications and shorter development cycles. Developers and companies are adopting solutions to increase productivity and reduce development time and effort. Among them, Model-driven Engineering (MDE) has emerged as a concrete alternative to automatically generate Android applications. However, the current MDE propositions generate only part of the application, forcing developers to spend time in implementation tasks. To tackle that, we propose JustModeling, an MDE approach formed by JBModel, a graphical modeling tool with which the user models the application business classes using the UML class diagram and that provides a set of model transformations to generate code for the JustBusiness framework, which automatically generates all necessary resources of the mobile application. This allows developers to work on a higher level of abstraction, focusing on the application design rather than implementation issues. The approach was validated by a case study that showed better results than JustBusiness and the traditional development.
Actin- and Dynamin-Dependent Maturation of Bulk Endocytosis Restores Neurotransmission following Synaptic Depletion

Bulk endocytosis contributes to the maintenance of neurotransmission at the amphibian neuromuscular junction by regenerating synaptic vesicles. How nerve terminals internalize adequate portions of the presynaptic membrane when bulk endocytosis is initiated before the end of a sustained stimulation is unknown. A maturation process, occurring at the end of the stimulation, is hypothesised to precisely restore the pools of synaptic vesicles. Using confocal time-lapse microscopy of FM1-43-labeled nerve terminals at the amphibian neuromuscular junction, we confirm that bulk endocytosis is initiated during a sustained tetanic stimulation and reveal that shortly after the end of the stimulation, nerve terminals undergo a maturation process. This includes a transient bulging of the plasma membrane, followed by the development of large intraterminal FM1-43-positive donut-like structures comprising large bulk membrane cisternae surrounded by recycling vesicles. The degree of bulging increased with stimulation frequency and the plasmalemma surface retrieved following the transient bulging correlated with the surface membrane internalized in bulk cisternae and recycling vesicles. Dyngo-4a, a potent dynamin inhibitor, did not block the initiation, but prevented the maturation of bulk endocytosis. In contrast, cytochalasin D, an inhibitor of actin polymerization, hindered both the initiation and maturation processes. Both inhibitors hampered the functional recovery of neurotransmission after synaptic depletion. Our data confirm that initiation of bulk endocytosis occurs during stimulation and demonstrates that a delayed maturation process controlled by actin and dynamin underpins the coupling between exocytosis and bulk endocytosis.