Scaling of the strange-metal scattering in unconventional superconductors.

Marked evolution of properties with minute changes in the doping level is a hallmark of the complex chemistry that governs copper oxide superconductivity as manifested in the celebrated superconducting domes and quantum criticality taking place at precise compositions1-4. The strange-metal state, in which the resistivity varies linearly with temperature, has emerged as a central feature in the normal state of copper oxide superconductors5-9. The ubiquity of this behaviour signals an intimate link between the scattering mechanism and superconductivity10-12. However, a clear quantitative picture of the correlation has been lacking. Here we report the observation of precise quantitative scaling laws among the superconducting transition temperature (Tc), the linear-in-T scattering coefficient (A1) and the doping level (x) in electron-doped copper oxide La2-xCexCuO4 (LCCO). High-resolution characterization of epitaxial composition-spread films, which encompass the entire overdoped range of LCCO, has enabled us to systematically map its structural and transport properties with unprecedented accuracy and with increments of Δx = 0.0015. We have uncovered the relations Tc ~ (xc - x)0.5 ~ (A1□)0.5, where xc is the critical doping in which superconductivity disappears and A1□ is the coefficient of the linear resistivity per CuO2 plane. The striking similarity of the Tc versus A1□ relation among copper oxides, iron-based and organic superconductors may be an indication of a common mechanism of the strange-metal behaviour and unconventional superconductivity in these systems.

Tetrameric Assembly of K+ Channels Requires ER-Located Chaperone Proteins.

Tetrameric assembly of channel subunits in the endoplasmic reticulum (ER) is essential for surface expression and function of K+ channels, but the molecular mechanism underlying this process remains unclear. In this study, we found through genetic screening that ER-located J-domain-containing chaperone proteins (J-proteins) are critical for the biogenesis and physiological function of ether-a-go-go-related gene (ERG) K+ channels in both Caenorhabditis elegans and human cells. Human J-proteins DNAJB12 and DNAJB14 promoted tetrameric assembly of ERG (and Kv4.2) K+ channel subunits through a heat shock protein (HSP) 70-independent mechanism, whereas a mutated DNAJB12 that did not undergo oligomerization itself failed to assemble ERG channel subunits into tetramers in vitro and in C. elegans. Overexpressing DNAJB14 significantly rescued the defective function of human ether-a-go-go-related gene (hERG) mutant channels associated with long QT syndrome (LQTS), a condition that predisposes to life-threatening arrhythmia, by stabilizing the mutated proteins. Thus, chaperone proteins are required for subunit stability and assembly of K+ channels.

Theoretical study of filtered and amplified PRBS phase modulation for SBS suppression in a 2.5†kW, 10†GHz monolithic fiber amplifier.

We report a theoretical and experimental study on stimulated Brillouin scattering (SBS) suppression in a monolithic fiber amplifier with filtered and amplified pseudo-random binary sequence (PRBS) phase modulation. Theoretically, we use a time-dependent three-wave coupled nonlinear system considering both active fiber and passive fiber to describe the acoustic phonon, laser, and Stokes characteristics in a fiber amplifier. The SBS threshold power after filtered PRBS phase modulation is numerically evaluated to obtain the optimal parameters, and the time-averaged distributions of the counter-pump power, laser power, and Stokes power at different positions along the fiber length of the fiber system are simulated. Also, we established a four-stage fiber amplifier system to verify our theory. The configuration of the fiber amplifier system includes a filtered and amplified PRBS phase-modulated single-frequency fiber laser, a three-stage pre-amplifier, and a counter-pumping main stage, subsequently. 2.5 kW output power with an FWHM linewidth of 9.63 GHz is accomplished by a domestic ytterbium-doped double-clad fiber with core/cladding diameters of 20.2/400  µm. The reflectivity of the main stage is 0.049‰ at the maximum output power, which indicates the proposed architecture is under the SBS threshold. The experiments verify the accuracy of the theoretical model, which provides a reliable reference for evaluating the SBS suppression capability of the high-power narrow-linewidth fiber amplifier phase modulated by the filtered and amplified PRBS signal.

3.05 kW, 13.7 GHz linewidth fiber amplifier based on PRBS phase modulation for SBS suppression.

In this paper, we establish a multi-stage fiber amplifier with pseudo-random binary sequence (PRBS) phase modulation. The stimulated Brillouin gain spectra of the main amplifier with both the unmodulated and pseudo-random binary sequence phase modulated configuration are measured (with corresponding output power), and the stimulated Brillouin scattering (SBS) threshold is investigated experimentally and theoretically. The pseudo-random binary sequence phase modulation parameters are optimized by theoretical simulation. With a two-stage preamplifier chain and a counter-pumping main amplifier stage, a maximum 3.05 kW output power with a slope efficiency of 85.9% is obtained experimentally. The central wavelength of the fiber amplifier is 1050 nm, associated with a full-width at half-maximum linewidth of 13.7 GHz. The stimulated Brillouin scattering reflectivity is below 0.01% at 3.05 kW at 13.7 GHz, which indicates that stimulated Brillouin scattering can be suppressed efficiently at this power and linewidth level.

Theoretical analysis of combining efficiency and beam quality degradation in a misaligned diffractive coherent combining system.

We theoretically investigate the combining efficiency and combined beam quality degradation induced by beam array misalignment in a coherent combining system based on diffractive optical elements. Theoretical model is established based on the Fresnel diffraction. We consider pointing aberration, positioning error and beam size deviation in array emitters as typical misalignments, and discuss their influences on beam combining by this model. The statistical analysis results and the accurate fitting curves of the degradation have been given based on the repetitive simulations with normal distributed random misalignments. According to the results, the combining efficiency is affected greatly by the pointing aberration and position error of the laser array, while the combined beam quality is just affected by the pointing aberration generally. Based on calculation with a series of typical parameters, the standard deviations of the laser array's pointing aberration and position error are required to less than 15µrad and 1µm respectively to maintain an excellent combining efficiency. If we only concentrate on the beam quality, the pointing aberration need to be less than 70µrad.

Comprehensive Analysis for Predicting Prognoses and Immune Responses of m6A-Related lncRNAs in Women with Lung Adenocarcinoma.

During the past decade, the average 5-year survival rate of patients with Lung adenocarcinoma (LUAD) has remained < 20%, although the targeted therapies and novel immunotherapy approaches have held promise. Epigenetic modifications could provide prognostic value as molecular biomarkers, and we aimed to identify the independent risk of m6A-related lncRNAs to establish a risk model for the clinical prediction of prognoses in women with LUAD. In this study, we first assessed 31 N6-methyladenosine (m6A)-related lncRNAs associated with overall survival. Moreover, we evaluated the expression of the oncogenic driver and the tumor immune microenvironment (TIME) in two female LUAD subtypes (clusters 1 and 2) using consensus clustering. We also found 16 m6A-related lncRNAs as the independent prognostic indicator of women with LUAD and established a risk model developed from these lncRNAs. We comprehensively investigated the correlation between the TIME and m6A-related lncRNA and found that m6A-related lncRNA may significantly affect the immune cell infiltration level in LUAD. In conclusion, our study provides evidence on the prognostic prediction in women with LUAD and may help elucidate the processes and mechanisms of m6A-regulated lncRNAs.

A Novel Deep Learning Model Based on Multi-Scale and Multi-View for Detection of Pulmonary Nodules.

Lung cancer manifests as pulmonary nodules in the early stage. Thus, the early and accurate detection of these nodules is crucial for improving the survival rate of patients. We propose a novel two-stage model for lung nodule detection. In the candidate nodule detection stage, a deep learning model based on 3D context information roughly segments the nodules detects the preprocessed image and obtain candidate nodules. In this model, 3D image blocks are input into the constructed model, and it learns the contextual information between the various slices in the 3D image block. The parameters of our model are equivalent to those of a 2D convolutional neural network (CNN), but the model could effectively learn the 3D context information of the nodules. In the false-positive reduction stage, we propose a multi-scale shared convolutional structure model. Our lung detection model has no significant increase in parameters and computation in both stages of multi-scale and multi-view detection. The proposed model was evaluated by using 888 computed tomography (CT) scans from the LIDC-IDRI dataset and achieved a competition performance metric (CPM) score of 0.957. The average detection sensitivity per scan was 0.971/1.0 FP. Furthermore, an average detection sensitivity of 0.933/1.0 FP per scan was achieved based on data from Shanghai Pulmonary Hospital. Our model exhibited a higher detection sensitivity, a lower false-positive rate, and better generalization than current lung nodule detection methods. The method has fewer parameters and less computational complexity, which provides more possibilities for the clinical application of this method.

A novel nonsense PKD1L1 variant cause heterotaxy syndrome with congenital asplenia in a Han Chinese patient.

Heterotaxy syndrome is a very rare congenital disease, which is caused by the disorder of left-right asymmetry during visceral development. However, pathogenic genetic lesions are found in less than 20% of HS patients. In this cohort study, whole-exome sequencing was performed for 110 patients with situs inversus or situs ambiguous. We identified a novel nonsense variant in PKD1L1(c.1387 C > T; p.463Gln*) in a Chinese patient with heterotaxy syndrome and congenital asplenia. This homozygous variant caused the domain of PKD1L1 complete absence. To our knowledge, this novel variant is the first phenotype of congenital asplenia found in patients with PKD1L1 variants, and the first PKD1L1 variant found in China. Our findings expand the spectrum of PKD1L1 variants and provide support for PKD1L1 variant and congenital asplenia, and the critical role of PKD1L1 during left-right patterning in the Han Chinese population.

Successful biventricular repair in a 14-year-old patient of asplenia with congenital heart disease syndrome.

Heterotaxy syndrome is a rare disease, and asplenia with congenital heart disease syndrome, also known as Ivemark syndrome, is a special form of heterotaxy syndrome. These patients usually have severe cardiovascular malformations and a poor prognosis. Their surgical outcomes are rarely satisfactory. We report the case of a 14-year-old patient who underwent successful corrective surgery treatment.

The influence of white matter hyperintensities severity on functional brain activity in cerebral small vessel disease: An rs-fMRI study.

OBJECTIVE: To investigate relationships between the severity of white matter hyperintensities (WMH), functional brain activity, and cognition in cerebral small vessel disease (CSVD) based on resting-state functional magnetic resonance imaging (rs-fMRI) data. METHODS: A total of 103 subjects with CSVD were included. The amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo), functional connectivity (FC) and their graph properties were applied to explore the influence of WMH burden on functional brain activity. We also investigated whether there are correlations between different functional brain characteristics and cognitive assessments. Finally, we selected disease-related rs-fMRI features in combination with ensemble learning to classify CSVD patients with low WMH load and with high WMH load. RESULTS: The high WMH load group demonstrated significantly abnormal functional brain activity based on rs-MRI data, relative to the low WMH load group. ALFF and graph properties in specific brain regions were significantly correlated with patients' cognitive assessments in CSVD. Moreover, altered rs-fMRI signal can help predict the severity of WMH in CSVD patients with an overall accuracy of 92.23%. CONCLUSIONS: This study provided a comprehensive analysis and evidence for a pattern of altered functional brain activity under different WMH load in CSVD based on rs-fMRI data, enabling accurately individual prediction of status of WMH.

Rational Design of Zinc/Zeolite Catalyst: Selective Formation of p-Xylene from Methanol to Aromatics Reaction.

The production of p-xylene from the methanol to aromatics (MTA) reaction is challenging. The catalytic stability, which is inversely proportional to the particle size of the zeolite, is not always compatible with p-xylene selectivity, which is inversely proportional to the external acid sites. In this study, based on a nano-sized zeolite, we designed hollow triple-shelled Zn/MFI single crystals using the ultra-dilute liquid-phase growth technique. The obtained composites possessed one ZSM-5 layer (≈30 nm) in the middle and two silicalite-1 layers (≈20 nm) epitaxially grown on two sides of ZSM-5, which exhibited a considerably long lifetime (100 % methanol conversion >40 h) as well as an enhanced shape selectivity of p-xylene (>35 %) with a p-xylene/xylene ratio of ≈90 %. Importantly, using this sandwich-like zeolite structure, we directly imaged the Zn species in the micropores of only the ZSM-5 layer and further determined the specific structure and anchor location of the Zn species.

Bi-allelic BRWD1 variants cause male infertility with asthenoteratozoospermia and likely primary ciliary dyskinesia.

Genetics-associated asthenoteratozoospermia is often seen in patients with multiple morphological abnormalities of the sperm flagella (MMAF). Although 24 causative genes have been identified, these explain only approximately half of patients with MMAF. Since sperm flagella and motile cilia (especially respiratory cilia) have similar axonemal structures, many patients with MMAF also exhibit respiratory symptoms, such as recurrent airway infection, chronic sinusitis, and bronchiectasis, which are frequently associated with primary ciliary dyskinesia (PCD), another recessive disorder. Here, exome sequencing was conducted to evaluate the genetic cause in 53 patients with MMAF and classic PCD/PCD-like symptoms. Two homozygous missense variants and a compound-heterozygous variant in the BRWD1 gene were identified in three unrelated individuals. BRWD1 staining was detected in the whole flagella and respiratory cilia of normal controls but was absent in BRWD1-mutated individuals. Transmission electron microscopy and immunostaining demonstrated that BRWD1 deficiency in human affected respiratory cilia and sperm flagella differently, as the absence of outer and inner dynein arms in sperm flagellum and respiratory cilia, while with a decreased number and outer doublet microtubule defects of respiratory cilia. To our knowledge, this is the first report of a BRWD1-variant-related disease in humans, manifesting as an autosomal recessive form of MMAF and PCD/PCD-like symptoms. Our data provide a basis for further exploring the molecular mechanism of BRWD1 gene during spermatogenesis and ciliogenesis.

High power pump and signal combiner for backward pumping structure with two different fused fiber bundle designs by means of pretapered pump fibers.

We report on two high power backward (6 + 1) × 1 pump and signal combiners with different optical designs based on end-pumping technique, each achieving more than 95% coupling ratio of signal light, 98% coupling ratio of pump light, and a total pump power of 2.95kW. Both designs solve the problem of non-uniform arrangement in asymmetric fiber bundles by the pretreatment of the pump fibers and signal fiber. Asymmetric fiber bundle in backward pump and signal combiners means the pump input fibers and signal output fiber have different cladding diameters. Two 3D simulation models were built to calculate the parameters of the fused fiber bundles for matching the mode field diameter between the signal input and the output fibers. Both optical designs of backward combiners were developed based on the beam propagation method and confirmed by experimental results.

Optimization and visualization of phase modulation with filtered and amplified maximal-length sequence for SBS suppression in a short fiber system: a theoretical treatment.

We use a model to investigate both the temporal and spectral characteristics of a signal lightwave which has been spectrally broadened through phase modulation with a maximal-length sequence (MLS), which is a common type of pseudo-random bit sequence. The enhancement of the stimulated Brillouin scattering (SBS) threshold of the modulated lightwave in a fiber system is evaluated by numerically simulating the coupled three-wave SBS interaction equations. We find that SBS can build up on a nanosecond-level time scale in a short fiber, which can reduce the SBS suppressing capability of MLS modulation waveforms with GHz-level clock rate, if the sub-sequence ("run") lengths with the same symbol (zero or one) of the MLS extend over several nanoseconds. To ensure the SBS buildup is perturbed and thus suppressed also during these long sub-sequences, we introduce a low-pass filter to average the signal over several bits so that the modulation waveform changes gradually even during long runs and amplify the RF modulation waveforms to the level required for sufficient spectral broadening and carrier suppression of the optical signal. We find that the SBS suppression depends non-monotonically on the parameters of the filtered and amplified MLS waveform such as pattern length, modulation depth, and the ratio of low-pass filter cutoff frequency to clock rate for maximum SBS mitigation. We optimize the SBS suppression through numerical simulations and discuss it in terms of the temporal and spectral characteristics of the lightwave and modulation waveform using derived analytical expressions and numerical simulations. The simulations indicate that the normalized SBS threshold reaches a maximum for a RMS modulation depth of 0.56π and a ratio of filter cutoff frequency to clock rate of 0.54 and that MLS9 is superior to other investigated patterns.

Investigation of combining-efficiency loss induced by a diffractive optical element in a single-aperture coherent beam combining system.

Filled-aperture geometries can be obtained using a diffractive optical element (DOE) in the coherent beam combining (CBC) architecture. Minimizing the beam deviation is crucial to maintain single-aperture output and reduce the combining-efficiency losses. In this study, we developed a theoretical model for investigating the combining-efficiency losses with beam deviation in a DOE-based CBC architecture. The beam deviations induced by the DOE-mount-tilt error, emitter-incident angular error, and DOE-groove-tilt error are discussed theoretically in detail and verified experimentally. The combining-efficiency losses caused by the three error sources are calculated. Meanwhile, the combining-efficiency losses affected by the beam size and the DOE period are analyzed. For an 11-channel CBC architecture with a DOE period of 50 µm and a beam size of 30 mm, the maximum combining-efficiency losses caused by the three error sources were 3.2%, 1.87%, and 36.41%, respectively, whereas those in case of a DOE period of 20 µm and a beam size of 10 mm were 14.34%, 8.58%, and 25.29%, respectively. We found that the combining-efficiency loss is most sensitive to the DOE-groove-tilt error.

Instantaneous response and suppression of SBS process in a short fiber system with binary sequence phase modulation.

We study the instantaneous response of stimulated Brillouin scattering (SBS) in a fiber system phase modulated by a binary sequence waveform. The buildup time constant of SBS kinetics is investigated analytically and experimentally. A series of binary sequences with adjustable dwell time and sequence period is constructed in order to examine both buildup and suppressing processes for SBS in 15 m short fiber. For a fiber system with SBS buildup time constant within several nanoseconds, the Stokes intensity can be effectively suppressed by implementing a binary sequence phase modulation with a dwell time close to or even less than the buildup time constant. Stokes intensity can be suppressed in several sequence periods, which exhibit a damped-oscillation-like trend.

RIP1/RIP3/MLKL-mediated necroptosis contributes to vinblastine-induced myocardial damage.

Vinblastine (VBL) has been considered as a first-line anti-tumor drug for many years. However, vinblastine-caused myocardial damage has been continually reported. The underlying molecular mechanism of the myocardial damage remains unknown. Here, we show that vinblastine induces myocardial damage and necroptosis is involved in the vinblastine-induced myocardial damage both in vitro and in vivo. The results of WST-8 and flow cytometry analysis show that vinblastine causes damage to H9c2 cells, and the results of animal experiments show that vinblastine causes myocardial cell damage. The necrosome components, receptor-interacting protein 1 (RIP1) receptor-interacting protein 3 (RIP3), are significantly increased in vinblastine-treated H9c2 cells, primary neonatal rat ventricular myocytes and rat heart tissues. And the downstream substrate of RIP3, mixed lineage kinase domain like protein (MLKL) was also increased. Pre-treatment with necroptosis inhibitors partially inhibits the necrosome components and MLKL levels and alleviates vinblastine-induced myocardial injury both in vitro and in vivo. This study indicates that necroptosis participated in vinblastine-evoked myocardial cell death partially, which would be a potential target for relieving the chemotherapy-related myocardial damage.

The impact of atrial fibrillation on outcomes in patients undergoing radical prostatectomy.

PURPOSE: To assess the role of atrial fibrillation (AF) on complicating inpatient outcomes of radical prostatectomy (RP). MATERIALS AND METHODS: We identified patients treated with RP during 2012-2014 within National Inpatient Sample (NIS) database. Length of stay, cost of hospitalization, and in-hospital complications were compared between patients with or without diagnosis of AF. Propensity score matching methods and multivariable regression analysis were used to adjust for potential confounders and a trend analysis was conducted. RESULTS: Patients with AF had a significantly longer hospital stay (coefficient 0.19, 95% CI 0.09-0.29, P < 0.001) and higher cost (coefficient 0.10, 95% CI 0.06-0.15, P < 0.001). Post-operative cardiac complications were significantly higher for patients with AF (OR 16.38, 95% CI 7.72-34.74, P < 0.001), while no differences were found in other complications between the two groups. Similar results were shown in propensity score matching methods. The cardiac complications after laparoscopic RP (OR: 37.71, 95% CI 1.85-768.73, P = 0.018) and open RP (OR: 16.78, 95% CI 1.41-199.51, P = 0.026) were significantly higher than robot-assisted RP (RARP) in patients with AF. The results of trend study indicated that postoperative cardiac complication rates showed a trend of decreasing year by year while the prevalence of AF was rising. CONCLUSIONS: Perioperative AF is associated with increased cardiac complications, longer hospital stay and higher cost in PCa patients undergoing RP. RARP may be a preferred choice for patients with AF. Attention should be paid to this special patient population. Reasonable pre-operative risk stratification and standardized management should be done to decrease perioperative complications.

The M310T mutation in the GATA4 gene is a novel pathogenic target of the familial atrial septal defect.

BACKGROUND: Although most cases of atrial septal defect (ASD) are sporadic, familial cases have been reported, which may be caused by mutation of transcription factor GATA binding protein 4 (GATA4). Herein we combined whole-exome sequencing and bioinformatics strategies to identify a novel mutation in GATA4 accounting for the etiology in a Chinese family with ASD. METHODS: We identified kindred spanning 3 generations in which 3 of 12 (25.0%) individuals had ASD. Punctilious records for the subjects included complete physical examination, transthoracic echocardiography, electrocardiograph and surgical confirming. Whole-exome capture and high-throughput sequencing were performed on the proband III.1. Sanger sequencing was used to validate the candidate variants, and segregation analyses were performed in the family members. RESULTS: Direct sequencing of GATA4 from the genomic DNA of family members identified a T-to-C transition at nucleotide 929 in exon 5 that predicted a methionine to threonine substitution at codon 310 (M310T) in the nuclear localization signal (NLS) region. Two affected members (II.2 and III.3) and the proband (III.1) who was recognized as a carrier exhibited this mutation, whereas the other unaffected family members or control individuals did not. More importantly, the mutation GATA4 (c.T929C: p.M310T) has not been reported previously in either familial or sporadic cases of congenital heart defects (CHD). CONCLUSIONS: We identified for the first time a novel M310T mutation in the GATA4 gene that is located in the NLS region and leads to family ASD with arrhythmias. However, the mechanism by which this pathogenic mutation contributes to the development of heart defect and tachyarrhythmias remains to be ascertained.

Detecting the Mechanism behind the Transition from Fixed Two-Dimensional Patterned Sika Deer (Cervus nippon) Dermal Papilla Cells to Three-Dimensional Pattern.

The hair follicle dermal papilla is critical for hair generation and de novo regeneration. When cultured in vitro, dermal papilla cells from different species demonstrate two distinguishable growth patterns under the conventional culture condition: a self-aggregative three dimensional spheroidal (3D) cell pattern and a two dimensional (2D) monolayer cell pattern, correlating with different hair inducing properties. Whether the loss of self-aggregative behavior relates to species-specific differences or the improper culture condition remains unclear. Can the fixed 2D patterned dermal papilla cells recover the self-aggregative behavior and 3D pattern also remains undetected. Here, we successfully constructed the two growth patterns using sika deer (Cervus nippon) dermal papilla cells and proved it was the culture condition that determined the dermal papilla growth pattern. The two growth patterns could transit mutually as the culture condition was exchanged. The fixed 2D patterned sika deer dermal papilla cells could recover the self-aggregative behavior and transit back to 3D pattern, accompanied by the restoration of hair inducing capability when the culture condition was changed. In addition, the global gene expressions during the transition from 2D pattern to 3D pattern were compared to detect the potential regulating genes and pathways involved in the recovery of 3D pattern and hair inducing capability.