Photoreceptor Cell Differentiation Requires Regulated Proteolysis of the Transcriptional Repressor Tramtrack

AbstractThe transcription repressor Tramtrack (TTK) is found in cone cells but not photoreceptor cells of the Drosophila eye. We show that down-regulation of TTK expression occurs in photoreceptor cells and is required for their fate determination. Down-regulation requires the presence of Phyllopod (PHYL), which is induced by the RAS pathway, and Seven In Absentia (SINA). Loss of either gene causes accumulation of TTK in photoreceptor cells, and TTK does not accumulate in cone cells if both PHYL and SINA are present. We report that SINA and PHYL promote ubiquitination and rapid degradation of TTK by the proteasome pathway in cell culture, and both SINA and PHYL bind to the N-terminal domain of TTK. These results argue that photoreceptor differentiation is regulated by the RAS pathway through targeted proteolysis of the TTK repressor

The Research of Reverse-Time Migration for Cross-Hole Seismic

Cross-hole seismic is the leading technology of development seismology, which is still developing and improving. With the development of down-hole acquisition equipment, cross-hole seismic acquisition technology is getting mature, providing better data for imaging. According to the features of cross-hole survey and cross-hole data, we put forward a reverse-time migration method which is suitable for the wave equation for cross-hole seismic data. We propose finite difference scheme of higher order, and then derive its stability condition in cross-hole seismic. The frequency dispersion problem in cross-hole seismic wave field extrapolation is also discussed. Cross correlation imaging condition is used to realize migration, and Laplace filter is applied to remove low-frequency noise from migration section. Thus finite-difference reverse-time migration method for cross-hole seismic is established. Finally, we build geological models with anomalous ellipsoids, and apply cross-hole seismic wave field simulation and migration to them, thus our method proves its effectiveness. When dealing with real cross-hole seismic data with this method, high-resolution migration sections can be achieved.Key words: Cross-hole seismic; Reverse-time migration; Model tes

Patterns of transcriptional parallelism and variation in the developing olfactory system of Drosophila species

Organisms have evolved strikingly parallel phenotypes in response to similar selection pressures suggesting that there may be shared constraints limiting the possible evolutionary trajectories. For example, the behavioral adaptation of specialist Drosophila species to specific host plants can exhibit parallel changes in their adult olfactory neuroanatomy. We investigated the genetic basis of these parallel changes by comparing gene expression during the development of the olfactory system of two specialist Drosophila species to that of four other generalist species. Our results suggest that the parallelism observed in the adult olfactory neuroanatomy of ecological specialists extends more broadly to their developmental antennal expression profiles, and to the transcription factor combinations specifying olfactory receptor neuron (ORN) fates. Additionally, comparing general patterns of variation for the antennal transcriptional profiles in the adult and developing olfactory system of the six species suggest the possibility that specific, non-random components of the developmental programs underlying the Drosophila olfactory system harbor a disproportionate amount of interspecies variation. Further examination of these developmental components may be able to inform a deeper understanding of how traits evolve

Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB

ObjectivesTo identify the molecular subtypes and develop a scoring system for the tumor immune microenvironment (TIME) and prognostic features of bladder cancer (BLCA) based on the platinum-resistance-related (PRR) genes analysis while identifying P4HB as a potential therapeutic target.MethodsIn this study, we analyzed gene expression data and clinical information of 594 BLCA samples. We used unsupervised clustering to identify molecular subtypes based on the expression levels of PRR genes. Functional and pathway enrichment analyses were performed to understand the biological activities of these subtypes. We also assessed the TIME and developed a prognostic signature and scoring system. Moreover, we analyzed the efficacy of immune checkpoint inhibitors. Then we conducted real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) experiments to detect the expression level of prolyl 4-hydroxylase subunit beta (P4HB) in BLCA cell lines. Transfection of small interference ribonucleic acid (siRNA) was performed in 5637 and EJ cells to knock down P4HB, and the impact of P4HB on cellular functions was evaluated through wound-healing and transwell assays. Finally, siRNA transfection of P4HB was performed in the cisplatin-resistant T24 cell to assess its impact on the sensitivity of BLCA to platinum-based chemotherapy drugs.ResultsIn a cohort of 594 BLCA samples (TCGA-BLCA, n=406; GSE13507, n=188), 846 PRR-associated genes were identified by intersecting BLCA expression data from TCGA and GEO databases with the PRR genes from the HGSOC-Platinum database. Univariate Cox regression analysis revealed 264 PRR genes linked to BLCA prognosis. We identified three molecular subtypes (Cluster A-C) and the PRR scoring system based on PRR genes. Cluster C exhibited a better prognosis and lower immune cell infiltration compared to the other Clusters A and B. The high PRR score group was significantly associated with an immunosuppressive tumor microenvironment, poor clinical-pathological features, and a poor prognosis. Furthermore, the high PRR group showed higher expression of immune checkpoint molecules and a poorer response to immune checkpoint inhibitors than the low PRR group. The key PRR gene P4HB was highly expressed in BLCA cell lines, and cellular functional experiments in vitro indicate that P4HB may be an important factor influencing BLCA migration and invasion.ConclusionOur study demonstrates that the PRR signatures are significantly associated with clinical-pathological features, the TIME, and prognostic features. The key PRR gene, P4HB, s a biomarker for the individualized treatment of BLCA patients

A 4 - 32 GHz SiGe Multi-Octave Power Amplifier with 20 dBm Peak Power, 18.6 dB Peak Gain and 156% Power Fractional Bandwidth

This letter presents the design and characterization results of a multi-octave power amplifier fabricated in a 0.13μm SiGe-BiCMOS technology. The single stage power amplifier is implemented as the stack of a cascode amplifier combining broadband input matching network with resistive feedback, and a common-base amplifier with base capacitive feedback. Measurement results show that the design delivers a peak saturated output power level of 20.2 dBm, with output 1 dB compression at 19.4 dBm. The measured 3 dB power bandwidth is from 4 GHz to 32 GHz, covering three octaves. The corresponding power fractional bandwidth is 156 %. The measured peak power added efficiency is 20.6 %, and peak small signal gain is 18.6 dB. The fabricated integrated circuit occupies an area of 0.71mm2. To compare state-of-the-art multi-octave power amplifiers, the power amplifier figure of merit defined by the international technology roadmap for semiconductors is modified to include power fractional bandwidth and area. To the knowledge of the authors, the presented design achieves the highest figure of merit among multi-octave power amplifiers in a silicon based integrated circuit technology reported in literature

Research on Bearing Capacity of Simply Supported Skew Bridge Based on Load Test

The purpose of this paper is to use static and dynamic load tests to evaluate the mechanical performance of a simply supported skew slab bridge and to evaluate its actual bearing capacity. Firstly, the Midas Civil software is used for theoretical simulation, and secondly, the deflection, strain, and dynamic response of the key section of the bridge are studied through static and dynamic load tests. Finally, the measured values and theoretical values are compared and analyzed. The results show that: under static load, the relative residual deflection and relative residual strain of the measuring point of the structure are between -13.8%～-0.4% and -16.7%～1.8% respectively; Under dynamic load, the first-order vertical natural frequency of the test section is 7.813, and the damping ratio is 0.0316, indicating that the bridge is in an elastic working state under the test load, and the stiffness and bearing capacity can meet the requirements of the current code

SAFETY ASSESSMENT OF CONTINUOUS CONCRETE GIRDER BRIDGES SUBJECTED TO RANDOM TRAFFIC LOADS CONSIDERING FLEXURAL-SHEAR COUPLED FAILURE

Bridges generally perform complicated mechanical behaviors under external loads, such as flexural-shear coupling, compression-bending coupling, and flexural-shear-torsion coupling. In the context of deterministic design approaches such as design codes, these complicated coupled issues are generally simplified to the safety verification of bridge components under a single mechanical state (i.e. flexural, shear, torsion). At present, the rapid development of sensor and information technologies makes it possible to collect the external loads acted on bridges and understand bridge performance under these stochastic external loads. In this manner, the reliability-based full probabilistic approach could be applied to investigate the performance of bridges over their lifetime. However, the current bridge reliability assessment incorporating realistic traffic load measurements mainly focuses on the analysis of bridge components under a single mechanical state. In this paper, a reliability-based probabilistic analytical framework of the flexural-shear performance of girder bridges under random traffic loading is established. The flexural-shear coupled failure path of bridge girders under random traffic loading is characterized for the first time, where the bivariate extreme value theory is incorporated to develop the extreme value distribution of combined flexural and shear load effects. The modified compression field theory recommended by AASHTO is employed to establish the coupled flexural-shear coupling resistances. Finally, the reliability of the flexural-shear performance of bridge girders is evaluated by solving the multivariate ultimate limit state equation. The proposed analytical framework is applied to a realistic bridge. The results show that the reliability index of the flexural-shear coupling evaluation is lower than that of the flexural or shear evaluation, which highlights the importance of the flexural-shear performance checking in the reliability assessment of bridges under random traffic loading. The proposed analytical framework could be further applied to the probabilistic assessment of bridge components subjected to combined loading mechanisms under random loadings

Phyllopod Acts as an Adaptor Protein To Link the Sina Ubiquitin Ligase to the Substrate Protein Tramtrack

The RING domain protein Sina, together with Phyllopod and the F-box protein Ebi, forms a Ras-regulated E3 ubiquitin ligase complex that activates photoreceptor cell differentiation in the eye of Drosophila melanogaster. The expression of Phyllopod is induced upon Ras activation, allowing the complex to degrade the transcription repressor Tramtrack and removing its block of neuronal development in photoreceptor precursors. We show that Phyllopod functions as an adaptor in the complex, physically linking Sina with Tramtrack via separate binding domains. One 19-amino-acid domain in Phyllopod interacts with a region of Sina's SBD domain. Another domain in Phyllopod interacts with a C-terminal helix in the POZ domain of Tramtrack. This interaction is specific to the Tramtrack POZ domain and not to other POZ domain proteins present in photoreceptor precursors. Degradation of Tramtrack is dependent upon association of Sina with its cognate binding site in Phyllopod. These results illustrate how Ras signaling can modulate an E3 ligase activity not by the phosphorylation of substrate proteins but by regulating the expression of specific E3 adaptors

A K-band SiGe Super-Regenerative Amplifier for FMCW Radar Active Reflector Applications

A K-band integrated super-regenerative amplifier (SRA) in a 130nm SiGe BiCMOS technology is designed and characterized. The circuit is based on a novel stacked transistor differential cross-coupled oscillator topology, with a controllable tail current for quenching the oscillations. The fabricated integrated circuit (IC) occupies an area of 0.63mm2, and operates at the free-running center frequency of 25.3 GHz. Characterization results show circuit operation from a minimum input power level required for a phase coherent output as −110 dBm, and the input power level corresponding to the linear to logarithmic mode transition of −85 dBm, the lowest reported for K-band integrated logarithmic mode SRAs to date to the knowledge of the authors. The measured output power is 7.8dBm into a 100 differential load. The power consumption of the circuit is 110mW with no quench signal applied, and 38mW with 30 % duty cycle quenching. The quench waveform designed for the reported measurement result is also discussed