Abnormal Silicon Etching Behaviors in Nanometer-Sized Channels.

Modern semiconductor fabrication is challenged by difficulties in overcoming physical and chemical constraints. A major challenge is the wet etching of dummy gate silicon, which involves the removal of materials inside confined spaces of a few nanometers. These chemical processes are significantly different in the nanoscale and bulk. Previously, electrical double-layer formation, bubble entrapment, poor wettability, and insoluble intermediate precipitation have been proposed. However, the exact suppression mechanisms remain unclear due to the lack of direct observation methods. Herein, we investigate limiting factors for the etching kinetics of silicon with tetramethylammonium hydroxide at the nanoscale by using liquid-phase transmission electron microscopy, three-dimensional electron tomography, and first-principles calculations. We reveal suppressed chemical reactions, unstripping phenomena, and stochastic etching behaviors that have never been observed on a macroscopic scale. We expect that solutions can be suggested from this comprehensive insight into the scale-dependent limiting factors of fabrication.

Enhanced Electrochemical Stability and Extended Cycle Life in Sulfide-Based All-Solid-State Batteries: The Role of Li10 SnP2 S12 Coating on Ni-Rich NCM Cathode.

Recently, sulfide-based all-solid-state batteries (ASSBs) have attracted great attention because of their excellent safety and high energy density. However, by-products formed from side-reactions between the oxide-based cathodes and sulfide-based solid electrolytes (SEs) increase the interfacial resistance and degrade the cell performance. Suppression of this interfacial resistance is thus critical. In this study, the extraordinarily high stability of the cathode/SE interface is discovered when a Li10 SnP2 S12 (LSnPS) is applied to a cathode buffer layer. The electrochemical properties of the cathode interface at high potential are improved by synthesizing a core-shell structure cathode using LSnPS. The synthesized LSnPS is uniformly coated on a Li2 ZrO3 -coated LiNi0.8 Co0.1 Mn0.1 O2 (LZO-NCM) surface using the cost-efficient mechano-fusion method. The ASSB with LSnPS-coated LZO-NCM as the cathode and Li6 PS5 Cl (argyrodite, LPSCl) as the SE exhibited a capacity of 192 mAh g-1 and excellent cycle retention of ≈75% after 500 charge/discharge cycles. In addition, the degradation mechanism at the cathode/SE interface is investigated. The results indicated that LSnPS stabilizes the interface between NCM and argyrodite, thereby inhibiting the decomposition of the SE. This technology is expected to contribute to the commercialization of cathode materials for sulfide-based ASSBs due to its enhanced cycle performance, low-cost material application, and eco-friendly process.

Predicting oxygen tension along the ureter.

Continuous measurement of bladder urine oxygen tension (Po2) is a method to potentially detect renal medullary hypoxia in patients at risk of acute kidney injury (AKI). To assess its practicality, we developed a computational model of the peristaltic movement of a urine bolus along the ureter and the oxygen exchange between the bolus and ureter wall. This model quantifies the changes in urine Po2 as urine transits from the renal pelvis to the bladder. The model parameters were calibrated using experimental data in rabbits, such that most of the model predictions are within ±1 SE of the reported mean in the experiment, with the average percent difference being 7.0%. Based on parametric experiments performed using a model scaled to the geometric dimensions of a human ureter, we found that bladder urine Po2 is strongly dependent on the bolus volume (i.e., bolus volume-to-surface area ratio), especially at a volume less than its physiological (baseline) volume (<0.2 mL). For the model assumptions, changes in peristaltic frequency resulted in a minimal change in bladder urine Po2 (<1 mmHg). The model also predicted that there exists a family of linear relationships between the bladder-urine Po2 and pelvic urine Po2 for different input conditions. We conclude that it may technically be possible to predict renal medullary Po2 based on the measurement of bladder urine Po2, provided that there are accurate real-time measurements of model input parameters.NEW & NOTEWORTHY Measurement of bladder urine oxygen tension has been proposed as a new method to potentially detect the risk of acute kidney injury in patients. A computational model of oxygen exchange between urine bolus and ureteral tissue shows that it may be technically possible to determine the risk of acute kidney injury based on the measurement of bladder urine oxygen tension, provided that the measurement data are properly interpreted via a computational model.

Effectiveness of pirfenidone in idiopathic pulmonary fibrosis according to the autoantibody status: a retrospective cohort study.

BACKGROUND: Pirfenidone is an anti-fibrotic agent shown to slow the progression of idiopathic pulmonary fibrosis (IPF). However, its effectiveness in association with serological autoimmune features in IPF remains unclear. METHODS: We retrospectively reviewed the medical records of patients with IPF treated at a tertiary care hospital in South Korea. The autoantibody status was defined as positive if we detected autoantibodies meeting the serological domain criteria for interstitial pneumonia with autoimmune features or anti-neutrophil cytoplasmic antibodies. RESULTS: We included 142 patients with IPF treated with pirfenidone for over six months (93 were autoantibody-positive and 49 were autoantibody-negative). The mean age was 69.5 ± 7.3 years, and 77.5% of the patients were male. The adjusted mean changes over one year were - 34.4 and - 112.2 mL (p = 0.168) in forced vital capacity (FVC), and - 0.53 and - 0.72 mL/mmHg/min (p = 0.356) in the lungs diffusion capacity for carbon monoxide (DLCO) in the autoantibody-negative and autoantibody-positive groups, respectively. CONCLUSIONS: Reductions in FVC and DLCO were similar in autoantibody-positive and autoantibody-negative patients with IPF treated with pirfenidone. Pirfenidone is effective in attenuating the progression of IPF, irrespective of the autoantibody status.

Attention-Based Joint Training of Noise Suppression and Sound Event Detection for Noise-Robust Classification.

Sound event detection (SED) recognizes the corresponding sound event of an incoming signal and estimates its temporal boundary. Although SED has been recently developed and used in various fields, achieving noise-robust SED in a real environment is typically challenging owing to the performance degradation due to ambient noise. In this paper, we propose combining a pretrained time-domain speech-separation-based noise suppression network (NS) and a pretrained classification network to improve the SED performance in real noisy environments. We use group communication with a context codec method (GC3)-equipped temporal convolutional network (TCN) for the noise suppression model and a convolutional recurrent neural network for the SED model. The former significantly reduce the model complexity while maintaining the same TCN module and performance as a fully convolutional time-domain audio separation network (Conv-TasNet). We also do not update the weights of some layers (i.e., freeze) in the joint fine-tuning process and add an attention module in the SED model to further improve the performance and prevent overfitting. We evaluate our proposed method using both simulation and real recorded datasets. The experimental results show that our method improves the classification performance in a noisy environment under various signal-to-noise-ratio conditions.

Luminance-Degradation Compensation Based on Multistream Self-Attention to Address Thin-Film Transistor-Organic Light Emitting Diode Burn-In.

We propose a deep-learning algorithm that directly compensates for luminance degradation because of the deterioration of organic light-emitting diode (OLED) devices to address the burn-in phenomenon of OLED displays. Conventional compensation circuits are encumbered by high cost of the development and manufacturing processes because of their complexity. However, given that deep-learning algorithms are typically mounted onto systems on chip (SoC), the complexity of the circuit design is reduced, and the circuit can be reused by only relearning the changed characteristics of the new pixel device. The proposed approach comprises deep-feature generation and multistream self-attention, which decipher the importance of the variables, and the correlation between burn-in-related variables. It also utilizes a deep neural network that identifies the nonlinear relationship between extracted features and luminance degradation. Thereafter, luminance degradation is estimated from burn-in-related variables, and the burn-in phenomenon can be addressed by compensating for luminance degradation. Experiment results revealed that compensation was successfully achieved within an error range of 4.56%, and demonstrated the potential of a new approach that could mitigate the burn-in phenomenon by directly compensating for pixel-level luminance deviation.

Direct Visualization of Lithium Polysulfides and Their Suppression in Liquid Electrolyte.

Understanding of lithium polysulfide (Li-PS) formation and the shuttle phenomenon is essential for practical application of the lithium/sulfur (Li/S) cell, which has superior theoretical specific energy (2600 Wh/kg). However, it suffers from the lack of direct observation on behaviors of soluble Li-PS in liquid electrolytes. Using in situ graphene liquid cell electron microscopy, we have visualized formation and diffusion of Li-PS simultaneous with morphological and phase evolutions of sulfur nanoparticles during lithiation. We found that the morphological changes and Li-PS diffusion are retarded by ionic liquid (IL) addition into electrolyte. Chronoamperometric shuttle current measurement confirms that IL addition lowers the experimental diffusion coefficient of Li-PS by 2 orders of magnitude relative to that in IL-free electrolyte and thus suppresses the Li-PS shuttle current, which accounts for better cyclability and Coulombic efficiency of the Li/S cell. This study provides significant insights into electrolyte design to inhibit the polysulfide shuttle phenomenon.

An adipocyte-specific defect in oxidative phosphorylation increases systemic energy expenditure and protects against diet-induced obesity in mouse models.

AIMS/HYPOTHESIS: Mitochondrial oxidative phosphorylation (OxPhos) is essential for energy production and survival. However, the tissue-specific and systemic metabolic effects of OxPhos function in adipocytes remain incompletely understood. METHODS: We used adipocyte-specific Crif1 (also known as Gadd45gip1) knockout (AdKO) mice with decreased adipocyte OxPhos function. AdKO mice fed a normal chow or high-fat diet were evaluated for glucose homeostasis, weight gain and energy expenditure (EE). RNA sequencing of adipose tissues was used to identify the key mitokines affected in AdKO mice, which included fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). For in vitro analysis, doxycycline was used to pharmacologically decrease OxPhos in 3T3L1 adipocytes. To identify the effects of GDF15 and FGF21 on the metabolic phenotype of AdKO mice, we generated AdKO mice with global Gdf15 knockout (AdGKO) or global Fgf21 knockout (AdFKO). RESULTS: Under high-fat diet conditions, AdKO mice were resistant to weight gain and exhibited higher EE and improved glucose tolerance. In vitro pharmacological and in vivo genetic inhibition of OxPhos in adipocytes significantly upregulated mitochondrial unfolded protein response-related genes and secretion of mitokines such as GDF15 and FGF21. We evaluated the metabolic phenotypes of AdGKO and AdFKO mice, revealing that GDF15 and FGF21 differentially regulated energy homeostasis in AdKO mice. Both mitokines had beneficial effects on obesity and insulin resistance in the context of decreased adipocyte OxPhos, but only GDF15 regulated EE in AdKO mice. CONCLUSIONS/INTERPRETATION: The present study demonstrated that the adipose tissue adaptive mitochondrial stress response affected systemic energy homeostasis via cell-autonomous and non-cell-autonomous pathways. We identified novel roles for adipose OxPhos and adipo-mitokines in the regulation of systemic glucose homeostasis and EE, which facilitated adaptation of an organism to local mitochondrial stress.

Risk Factors for Cytomegalovirus Reactivation in Lung Transplant Recipients.

PURPOSE: We examined risk factors that may have contributed to Cytomegalovirus (CMV) reactivation among patients who underwent lung transplantation (LTx). METHODS: We reviewed medical records of patients who underwent LTx at a tertiary healthcare hospital in South Korea between January 2013 and May 2017. We excluded patients who died within the first year after LTx and those lost to follow-up. CMV reactivation was defined as the detection of CMV titers above 3000 copies/ml regardless of specific symptoms after prophylaxis cessation. RESULTS: Of 89 patients included, 39 (43.8%) developed CMV reactivation. Of those 39 patients, 16 (41.0%) experienced additional CMV reactivation. Multivariate analysis identified lymphocyte counts below 1.0 × 103/µl (hazard ratio [HR] 49.33, p < 0.001) and use of steroids at more than twice the standard dose (HR 8.07, p < 0.001) as risk factors for CMV reactivation. The multivariate model also identified chronic kidney disease (CKD; HR 5.19, p = 0.016) and pneumonia (HR 17.22, p = 0.013) as risk factors for repetitive CMV reactivation. CONCLUSION: This study suggests that lymphopenia and high doses of steroids may be important risk factors for CMV reactivation in LTx patients. Our results also suggest that repetitive CMV reactivation may be associated with CKD and pneumonia.

Joint Optimization of Deep Neural Network-Based Dereverberation and Beamforming for Sound Event Detection in Multi-Channel Environments.

In this paper, we propose joint optimization of deep neural network (DNN)-supported dereverberation and beamforming for the convolutional recurrent neural network (CRNN)-based sound event detection (SED) in multi-channel environments. First, the short-time Fourier transform (STFT) coefficients are calculated from multi-channel audio signals under the noisy and reverberant environments, which are then enhanced by the DNN-supported weighted prediction error (WPE) dereverberation with the estimated masks. Next, the STFT coefficients of the dereverberated multi-channel audio signals are conveyed to the DNN-supported minimum variance distortionless response (MVDR) beamformer in which DNN-supported MVDR beamforming is carried out with the source and noise masks estimated by the DNN. As a result, the single-channel enhanced STFT coefficients are shown at the output and tossed to the CRNN-based SED system, and then, the three modules are jointly trained by the single loss function designed for SED. Furthermore, to ease the difficulty of training a deep learning model for SED caused by the imbalance in the amount of data for each class, the focal loss is used as a loss function. Experimental results show that joint training of DNN-supported dereverberation and beamforming with the SED model under the supervision of focal loss significantly improves the performance under the noisy and reverberant environments.

Multi-TALK: Multi-Microphone Cross-Tower Network for Jointly Suppressing Acoustic Echo and Background Noise.

In this paper, we propose a multi-channel cross-tower with attention mechanisms in latent domain network (Multi-TALK) that suppresses both the acoustic echo and background noise. The proposed approach consists of the cross-tower network, a parallel encoder with an auxiliary encoder, and a decoder. For the multi-channel processing, a parallel encoder is used to extract latent features of each microphone, and the latent features including the spatial information are compressed by a 1D convolution operation. In addition, the latent features of the far-end are extracted by the auxiliary encoder, and they are effectively provided to the cross-tower network by using the attention mechanism. The cross tower network iteratively estimates the latent features of acoustic echo and background noise in each tower. To improve the performance at each iteration, the outputs of each tower are transmitted as the input for the next iteration of the neighboring tower. Before passing through the decoder, to estimate the near-end speech, attention mechanisms are further applied to remove the estimated acoustic echo and background noise from the compressed mixture to prevent speech distortion by over-suppression. Compared to the conventional algorithms, the proposed algorithm effectively suppresses the acoustic echo and background noise and significantly lowers the speech distortion.

Analysis of the critical determinants of renal medullary oxygenation.

We have previously developed a three-dimensional computational model of oxygen transport in the renal medulla. In the present study, we used this model to quantify the sensitivity of renal medullary oxygenation to four of its major known determinants: medullary blood flow (MBF), medullary oxygen consumption rate (V̇o2,M), hemoglobin (Hb) concentration in the blood, and renal perfusion pressure. We also examined medullary oxygenation under special conditions of hydropenia, extracellular fluid volume expansion by infusion of isotonic saline, and hemodilution during cardiopulmonary bypass. Under baseline (normal) conditions, the average medullary tissue Po2 predicted for the whole renal medulla was ~30 mmHg. The periphery of the interbundle region in the outer medulla was identified as the most hypoxic region in the renal medulla, which demonstrates that the model prediction is qualitatively accurate. Medullary oxygenation was most sensitive to changes in renal perfusion pressure followed by Hb, MBF, and V̇o2,M, in that order. The medullary oxygenation also became sensitized by prohypoxic changes in other parameters, leading to a greater fall in medullary tissue Po2 when multiple parameters changed simultaneously. Hydropenia did not induce a significant change in medullary oxygenation compared with the baseline state, while volume expansion resulted in a large increase in inner medulla tissue Po2 (by ~15 mmHg). Under conditions of cardiopulmonary bypass, the renal medulla became severely hypoxic, due to hemodilution, with one-third of the outer stripe of outer medulla tissue having a Po2 of <5 mmHg.

Stimulation of erythropoietin release by hypoxia and hypoxemia: similar but different.

Erythropoietin is released from the kidney in response to tissue hypoxia. Montero and Lundby found that increases in plasma erythropoietin induced by reducing arterial oxygen content in healthy humans were independent of arterial oxygen tension. Their observations accord with the established physiology of kidney oxygenation and can be predicted by a computational model of renal oxygen transport. However, model simulations indicate that the interpretation implicit in the title of their paper may be an oversimplification.

Thoracic skeletal muscle quantification: low muscle mass is related with worse prognosis in idiopathic pulmonary fibrosis patients.

BACKGROUND: Sarcopenia can contribute to negative outcomes in patients with various lung diseases. However, whether sarcopenia affects prognosis in patients with idiopathic pulmonary fibrosis (IPF) has not been reported. Simple measures of muscle mass, derived from chest computed tomography (CT), are increasingly being used to identify patients with sarcopenia. We hypothesized that skeletal muscle mass could be a predictor of prognosis in IPF patients. METHODS: We retrospectively evaluated 180 patients diagnosed with IPF between January 2010 and December 2015 at a tertiary care hospital in South Korea. We measured thoracic muscle volume by using the cross-sectional area (CSA) of the pectoralis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA) and the erector spinae muscle (ESMCSA) at the 12th vertebral region. CT scans at the time of diagnosis were used for analysis and respective CSA were divided by height squared to normalize for stature. Survival times were estimated with the Kaplan-Meier method and compared with the log-rank test. Multivariate Cox proportional hazards models were performed to investigate relationships between clinical parameters and mortality. RESULTS: Male patients in the lowest quartile of T4CSA divided by height squared (m2) (T4MI) and in the lowest quartile of ESMCSA divided by height squared (m2) (T12MI) were more likely to have higher Gender-Age-Physiology Index scores (T4MI, 3.3 ± 1.3 vs 4.0 ± 1.6, P = 0.012; T12MI, 3.2 ± 1.3 vs 4.1 ± 1.6, P = 0.002). Male patients in the lowest quartile of T4MI exhibited a significantly lower survival rate (P = 0.035). After multivariate Cox proportional hazards analysis, T4MI was a significant risk factor for all-cause mortality (HR, 0.955; 95% CI, 0.913-0.998; P = 0.041), whereas T12MI was not (HR, 0.980; 95% CI, 0.856-1.121; P = 0.766). CONCLUSIONS: Low skeletal mass normalized for stature at the level of 4th vertebrae which can be acquired by quantifying thoracic skeletal muscle on single-slice axial chest CT, may be a strong risk factor for all-cause mortality in patients with IPF. TRIAL REGISTRATION: The research protocol was approved by the Institutional Review Board of Severance Hospital, South Korea (IRB No.4-2018-0454).

Prognostic impact of the ratio of the main pulmonary artery to that of the aorta on chest computed tomography in patients with idiopathic pulmonary fibrosis.

BACKGROUND: In many clinical disorders, there is a relationship between the ratio of the diameter of the main pulmonary artery (mPA) to that of the aorta (Ao) on chest computed tomography (CT). The aim of this study was to determine if the mPA/Ao ratio at diagnosis is associated with the clinical characteristics and outcomes in patients with idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively reviewed the diameters of the pulmonary artery and aorta on chest CT, clinical characteristics, and results of other examinations in 303 patients at the time of initial diagnosis of IPF at our tertiary care center between 2011 and 2015. The primary outcomes were death and lung transplantation. The patients were followed up until June 2017. RESULTS: One hundred and eight patients (35.6%) died and 58 (19.1%) underwent lung transplantation during follow-up. The mean mPA and Ao diameters were 28.3 mm and 34.0 mm, respectively, and the mean mPA/Ao ratio was 0.84. Thirty-one patients (10.2%) had an mPA/Ao ratio > 1.0 and 182 (60.1%) had an mPA/Ao ratio > 0.8. Patients with an mPA/Ao ratio > 0.8 had a lower DLco value than those with an mPA/Ao ratio ≤ 0.8. In Kaplan-Meier analysis, patients with an mPA/Ao ratio > 1.0 or > 0.8 had worse outcomes than those with an mPA/Ao ratio ≤ 1.0 and ≤ 0.8, respectively. CONCLUSIONS: A higher mPA/Ao ratio based on 1.0 and 0.8 is associated with unfavorable prognosis in patients with IPF.

Sports injury and illness incidence in the PyeongChang 2018 Olympic Winter Games: a prospective study of 2914 athletes from 92 countries.

OBJECTIVE: To describe the incidence of injuries and illnesses sustained during the XXIII Olympic Winter Games, hosted by PyeongChang on 9-25 February 2018. METHODS: We recorded the daily number of athlete injuries and illnesses (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the PyeongChang 2018 medical staff. RESULTS: In total, 2914 athletes (1210 women, 42%; 1704 men, 58%) from 92 NOCs were observed for occurrence of injury and illness. NOC and PyeongChang 2018 medical staff reported 376 injuries and 279 illnesses, equalling 12.6 injuries and 9.4 illnesses per 100 athletes over the 17-day period. Altogether, 12% of the athletes incurred at least one injury and 9% at least one illness. The injury incidence was highest in ski halfpipe (28%), snowboard cross (26%), ski cross (25%), snowboard slopestyle (21%) and aerials (20%), and lowest in Nordic combined, biathlon, snowboard slalom, moguls and cross-country skiing (2%-6%). Of the 376 injuries recorded, 33% and 13% were estimated to lead to ≥1 day and >7 days of absence from sport, respectively. The highest incidences of illness were recorded in biathlon (15%), curling (14%), bobsleigh (14%) and snowboard slalom (13%). Thirty per cent of the illnesses were expected to result in time loss, and 70% affected the respiratory system. Women suffered 61% more illnesses than men. CONCLUSION: Overall, 12% of the athletes incurred at least one injury during the Games and 9% an illness, incidences that are similar to the Olympic Winter Games of 2010 and 2014.

Erythropoietin-Producing Hepatoma Receptor Tyrosine Kinase A2 Modulation Associates with Protective Effect of Prone Position in Ventilator-induced Lung Injury.

The erythropoietin-producing hepatoma (Eph) receptor tyrosine kinase A2 (EphA2) and its ligand, ephrinA1, play a pivotal role in inflammation and tissue injury by modulating the epithelial and endothelial barrier integrity. Therefore, EphA2 receptor may be a potential therapeutic target for modulating ventilator-induced lung injury (VILI). To support this hypothesis, here, we analyzed EphA2/ephrinA1 signaling in the process of VILI and determined the role of EphA2/ephrinA1 signaling in the protective mechanism of prone positioning in a VILI model. Wild-type mice were ventilated with high (24 ml/kg; positive end-expiratory pressure, 0 cm; 5 h) tidal volume in a supine or prone position. Anti-EphA2 receptor antibody or IgG was administered to the supine position group. Injury was assessed by analyzing the BAL fluid, lung injury scoring, and transmission electron microscopy. Lung lysates were evaluated using cytokine/chemokine ELISA and Western blotting of EphA2, ephrinA1, PI3Kγ, Akt, NF-κB, and P70S6 kinase. EphA2/ephrinA1 expression was higher in the supine high tidal volume group than in the control group, but it did not increase upon prone positioning or anti-EphA2 receptor antibody treatment. EphA2 antagonism reduced the extent of VILI and downregulated the expression of PI3Kγ, Akt, NF-κB, and P70S6 kinase. These findings demonstrate that EphA2/ephrinA1 signaling is involved in the molecular mechanism of VILI and that modulation of EphA2/ehprinA1 signaling by prone position or EphA2 antagonism may be associated with the lung-protective effect. Our data provide evidence for EphA2/ehprinA1 as a promising therapeutic target for modulating VILI.

A model of oxygen transport in the rat renal medulla.

The renal medulla is prone to hypoxia. Medullary hypoxia is postulated to be a leading cause of acute kidney injury, so there is considerable interest in predicting the oxygen tension in the medulla. Therefore we have developed a computational model for blood and oxygen transport within a physiologically normal rat renal medulla, using a multilevel modeling approach. For the top-level model we use the theory of porous media and advection-dispersion transport through a realistic three-dimensional representation of the medulla's gross anatomy to describe blood flow and oxygen transport throughout the renal medulla. For the lower-level models, we employ two-dimensional reaction-diffusion models describing the distribution of oxygen through tissue surrounding the vasculature. Steady-state model predictions at the two levels are satisfied simultaneously, through iteration between the levels. The computational model was validated by simulating eight sets of experimental data regarding renal oxygenation in rats (using 4 sets of control groups and 4 sets of treatment groups, described in 4 independent publications). Predicted medullary tissue oxygen tension or microvascular oxygen tension for control groups and for treatment groups that underwent moderate perturbation in hemodynamic and renal functions is within ±2 SE values observed experimentally. Diffusive shunting between descending and ascending vasa recta is predicted to be only 3% of the oxygen delivered. The validation tests confirm that the computational model is robust and capable of capturing the behavior of renal medullary oxygenation in both normal and early-stage pathological states in the rat.

Anosmin-1 is essential for neural crest and cranial placodes formation in Xenopus.

During embryogenesis vertebrates develop a complex craniofacial skeleton associated with sensory organs. These structures are primarily derived from two embryonic cell populations the neural crest and cranial placodes, respectively. Neural crest cells and cranial placodes are specified through the integrated action of several families of signaling molecules, and the subsequent activation of a complex network of transcription factors. Here we describe the expression and function of Anosmin-1 (Anos1), an extracellular matrix protein, during neural crest and cranial placodes development in Xenopus laevis. Anos1 was identified as a target of Pax3 and Zic1, two transcription factors necessary and sufficient to generate neural crest and cranial placodes. Anos1 is expressed in cranial neural crest progenitors at early neurula stage and in cranial placode derivatives later in development. We show that Anos1 function is required for neural crest and sensory organs development in Xenopus, consistent with the defects observed in Kallmann syndrome patients carrying a mutation in ANOS1. These findings indicate that anos1 has a conserved function in the development of craniofacial structures, and indicate that anos1-depleted Xenopus embryos represent a useful model to analyze the pathogenesis of Kallmann syndrome.

Inhibition of insulin-like growth factor receptor-1 reduces necroptosis-related markers and attenuates LPS-induced lung injury in mice.

Insulin-like growth factor-1 (IGF-1) levels are known to increase in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome. Herein, we investigated the role of IGF-1 in lipopolysaccharide (LPS)-induced lung injury. In LPS-treated cells, expressions of receptor-interacting protein 3 (RIP3) and phosphorylated mixed lineage kinase domain-like protein (MLKL) were decreased in IGF-1 receptor small interfering RNA (siRNA)-treated cells compared to control cells. The levels of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, IL-10, tumour necrosis factor-α, and macrophage inflammatory protein 2/C-X-C motif chemokine ligand 2 in the supernatant were significantly reduced in IGF-1 receptor siRNA-treated cells compared to control cells. In LPS-induced murine lung injury model, total cell counts, polymorphonuclear leukocytes counts, and pro-inflammatory cytokine levels in the BALF were significantly lower and histologically detected lung injury was less common in the group treated with IGF-1 receptor monoclonal antibody compared to the non-treated group. On western blotting, RIP3 and phosphorylated MLKL expressions were relatively decreased in the IGF-1 receptor monoclonal antibody group compared to the non-treated group. IGF-1 may be associated with RIP3-mediated necroptosis in vitro, while blocking of the IGF-1 pathway may reduce LPS-induced lung injuries in vivo.