Site-1 protease deficiency causes human skeletal dysplasia due to defective inter-organelle protein trafficking

Site-1 protease (S1P), encoded by MBTPS1, is a serine protease in the Golgi. S1P regulates lipogenesis, endoplasmic reticulum (ER) function, and lysosome biogenesis in mice and in cultured cells. However, how S1P differentially regulates these diverse functions in humans has been unclear. In addition, no human disease with S1P deficiency has been identified. Here, we report a pediatric patient with an amorphic and a severely hypomorphic mutation in MBTPS1. The unique combination of these mutations results in a frequency of functional MBTPS1 transcripts of approximately 1%, a finding that is associated with skeletal dysplasia and elevated blood lysosomal enzymes. We found that the residually expressed S1P is sufficient for lipid homeostasis but not for ER and lysosomal functions, especially in chondrocytes. The defective S1P function specifically impairs activation of the ER stress transducer BBF2H7, leading to ER retention of collagen in chondrocytes. S1P deficiency also causes abnormal secretion of lysosomal enzymes due to partial impairment of mannose-6-phosphate-dependent delivery to lysosomes. Collectively, these abnormalities lead to apoptosis of chondrocytes and lysosomal enzyme-mediated degradation of the bone matrix. Correction of an MBTPS1 variant or reduction of ER stress mitigated collagen-trafficking defects. These results define a new congenital human skeletal disorder and, more importantly, reveal that S1P is particularly required for skeletal development in humans. Our findings may also lead to new therapies for other genetic skeletal diseases, as ER dysfunction is common in these disorders

Water vapour corrosion of rare earth monosilicates for environmental barrier coatings application

Water vapour corrosion resistance of five rare earth monosilicates Y2SiO5, Gd2SiO5, Er2SiO5, Yb2SiO5, and Lu2SiO5 was investigated during testing at 1350 ˚C for up to 166 h in static air with 90% water vapour. Four of the RE-silicates showed little weight gain (0.859 mg cm-2) after 166 h of exposure. Prior to testing the microstrucre consists of equiaxed grains of 4- 7 ± 0.4 µm. XRD analysis showed that after 50 h exposure to water vapour corrosion Y, Er, Yb and Lu-silicates had both mono and disilicates present on their surfaces as a result of the reaction between monosilicate and water vapour to form disilicate, while Gd-silicate has converted completely to G4.67Si3O13 making it less stable for environmental barrier coatings application. The microstructures of corroded Y, Er, Yb and Lu-silicates contain ridges and cracks, while that of Gd-silicate contains rounded grains suggesting melting along with striped contract grains

Greykite: Deploying Flexible Forecasting at Scale at LinkedIn

Forecasts help businesses allocate resources and achieve objectives. At LinkedIn, product owners use forecasts to set business targets, track outlook, and monitor health. Engineers use forecasts to efficiently provision hardware. Developing a forecasting solution to meet these needs requires accurate and interpretable forecasts on diverse time series with sub-hourly to quarterly frequencies. We present Greykite, an open-source Python library for forecasting that has been deployed on over twenty use cases at LinkedIn. Its flagship algorithm, Silverkite, provides interpretable, fast, and highly flexible univariate forecasts that capture effects such as time-varying growth and seasonality, autocorrelation, holidays, and regressors. The library enables self-serve accuracy and trust by facilitating data exploration, model configuration, execution, and interpretation. Our benchmark results show excellent out-of-the-box speed and accuracy on datasets from a variety of domains. Over the past two years, Greykite forecasts have been trusted by Finance, Engineering, and Product teams for resource planning and allocation, target setting and progress tracking, anomaly detection and root cause analysis. We expect Greykite to be useful to forecast practitioners with similar applications who need accurate, interpretable forecasts that capture complex dynamics common to time series related to human activity.Comment: In Proceedings of the 28th ACM SIGKDD Conference on Knowledge Discovery and Data Mining (KDD '22), August 14-18, 2022, Washington, DC, USA. ACM, New York, NY, USA, 11 page

Search for charged lepton flavor violating decays of ϒ (1S)

We present a search for the charged lepton-flavor-violating decays ϒ(1S) →ℓ±ℓ′∓ and radiative charged lepton-flavour-violating decays ϒ(1S) → γℓ±ℓ′∓ [ℓ,ℓ′ = e, μ, τ] using the 158 million ϒ(2S) sample collected by the Belle detector at the KEKB collider. This search uses ϒ(1S) mesons produced in ϒ(2S) → π+π− ϒ(1S) transitions. We do not find any significant signal, so we provide upper limits on the branching fractions at the 90% confidence level. [Figure not available: see fulltext.] © 2022, The Author(s)

Propagation of squeezed radiation through amplifying or absorbing random media

We analyse how nonclassical features of squeezed radiation (in particular the sub-Poissonian noise) are degraded when it is transmitted through an amplifying or absorbing medium with randomly located scattering centra. Both the cases of direct photodetection and of homodyne detection are considered. Explicit results are obtained for the dependence of the Fano factor (the ratio of the noise power and the mean current) on the degree of squeezing of the incident state, on the length and the mean free path of the medium, the temperature, and on the absorption or amplification rate.Comment: 8 pages, 4 figure

Chloroquine and hydroxychloroquine for the prevention and treatment of COVID-19: A fiction, hope or hype? An updated review

In December 2019, the novel coronavirus disease pandemic (COVID-19) that began in China had infected so far more than 109,217,366 million individuals worldwide and accounted for more than 2,413,912 fatalities. With the dawn of this novel coronavirus (SARS-CoV-2), there was a requirement to select potential therapies that might effectively kill the virus, accelerate the recovery, or decrease the case fatality rate. Besides the currently available antiviral medications for human immunodeficiency virus (HIV) and hepatitis C virus (HCV), the chloroquine/hydroxychloroquine (CQ/HCQ) regimen with or without azithromycin has been repurposed in China and was recommended by the National Health Commission, China in mid-February 2020. By this time, the selection of this regimen was based on its efficacy against the previous SARS-CoV-1 virus and its potential to inhibit viral replication of the SARS-CoV-2 in vitro. There was a shortage of robust clinical proof about the effectiveness of this regimen against the novel SARS-CoV-2. Therefore, extensive research effort has been made by several researchers worldwide to investigate whether this regimen is safe and effective for the management of COVID-19. In this review, we provided a comprehensive overview of the CQ/HCQ regimen, summarizing data from in vitro studies and clinical trials for the protection against or the treatment of SARS-CoV-2. Despite the initial promising results from the in vitro studies and the widespread use of CQ/HCQ in clinical settings during the 1st wave of COVID-19, current data from well-designed randomized controlled trials showed no evidence of benefit from CQ/HCQ supplementation for the treatment or prophylaxis against SARS-CoV-2 infection. Particularly, the two largest randomized controlled trials to date (RECOVERY and WHO SOLIDARITY trials), both confirmed that CQ/HCQ regimen does not provide any clinical benefit for COVID-19 patients. Therefore, we do not recommend the use of this regimen in COVID-19 patients outside the context of clinical trials

Oxidation behaviour of SiC/SiC ceramic matrix composites in air

Oxidation of silicon melt infiltrated SiC/SiC ceramic matrix composites (CMC) was studied in air at 1200–1400 °C for 1, 5, 24 and 48 h. Weight gain and oxide layer thickness measurements revealed the oxidation follows parabolic reaction kinetics with increase in temperature and time. XRD showed the extent of oxide layer (SiO2) formation was greatest after 48 h at 1400 °C: an observation confirmed by X-ray photoelectron spectroscopy (XPS), energy dispersive spectroscopy (EDS) and transmission electron microscopy (TEM) analyses. Oxide layer thickness varied from 1 μm after 48 h at 1200 °C to 8 μm after 48 h at 1400 °C. Oxidation of SiC/SiC composites is both temperature and time dependent with an activation energy of 619 kJ mol−1. BN coatings around SiC fibres showed good resistance to oxidation even after 48 h at 1400 °C

Phosphate ion removal from synthetic and real wastewater using MnFe2O4 nanoparticles: a reusable adsorbent

The purpose of this study was to eliminate phosphate (P) from wastewater using MnFe2O4 nanoparticles. BET, TGA/DTG, FTIR, SEM, TEM, VSM, XRD and EDX/Map analyses were used to determine the MnFe2O4 surface properties. The specific surface area of the adsorbent was 196.56 m2/g and VSM analysis showed that the adsorbent has a ferromagnetic property. The maximum P sorption efficiency using MnFe2O4 (98.52%) was achieved at pH 6, temperature of 55 °C, P concentration of 10 mg/L, time of 60 min, and sorbent dosage of 2.5 g/L, which is a significant value. Also, the thermodynamic study indicated that the P sorption process is spontaneous and endothermic. Moreover, the utmost sorption capacity of P using MnFe2O4 was 39.48 mg/g. Besides, MnFe2O4 can be used for up to 6 reuse cycles with high sorption efficiency (>91%). Also, MnFe2O4 was able to remove phosphate, COD, and BOD5 from municipal wastewater with considerable removal efficiencies of 82.7%, 75.8%, and 77.3%, respectively.Campus Lima Centr

An Efficient Ultrasound-Assisted Synthesis of Cu/Zn Hybrid MOF Nanostructures With High Microbial Strain Performance

Metal organic frameworks (MOFs) are a promising choice for antibacterial and antifungal activity due to their composition, unique architecture, and larger surface area. Herein, the ultrasonic method was used to synthesize the Cu/Zn-MOF material as an effective hybrid nanostructure with ideal properties. SEM images were used to investigate the product’s morphology and particle size distribution. The XRD pattern revealed that the Cu/Zn hybrid MOF nanostructures had a smaller crystalline size distribution than pure Cu and Zn-MOF samples. Furthermore, the BET technique determined that the hybrid MOF nanostructures had a high specific surface area. TG analysis revealed that the hybrid MOF structures were more thermally stable than pure samples. The final product, with remarkable properties, was used as a new option in the field of antibacterial studies. Antibacterial activity was assessed using MIC and MBC against Gram negative and Gram positive strains, as well as antifungal activity using MIC and MFC. The antimicrobial properties of the synthesized Cu/Zn hybrid MOF nanostructures revealed that they were more effective than commercial drugs in some cases. This study’s protocol could be a new strategy for introducing new hybrid nanostructures with specific applications