Growing regulatory requirements set barriers around genetic data sharing and collaborations. Moreover, existing privacy-aware paradigms are challenging to deploy in collaborative settings. We present ...COLLAGENE, a tool base for building secure collaborative genomic data analysis methods. COLLAGENE protects data using shared-key homomorphic encryption and combines encryption with multiparty strategies for efficient privacy-aware collaborative method development. COLLAGENE provides ready-to-run tools for encryption/decryption, matrix processing, and network transfers, which can be immediately integrated into existing pipelines. We demonstrate the usage of COLLAGENE by building a practical federated GWAS protocol for binary phenotypes and a secure meta-analysis protocol. COLLAGENE is available at https://zenodo.org/record/8125935 .
Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is an evolutionarily conserved nicotinamide adenine dinucleotide (NAD+) synthase located in the cytoplasm and Golgi apparatus. NMNAT2 has an ...important role in neurodegenerative diseases, malignant tumors, and other diseases that seriously endanger human health. NMNAT2 exerts a neuroprotective function through its NAD synthase activity and chaperone function. Among them, the NMNAT2-NAD+-Sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) axis is closely related to Wallerian degeneration. Physical injury or pathological stimulation will cause a decrease in NMNAT2, which activates SARM1, leading to axonal degeneration and the occurrence of amyotrophic lateral sclerosis (ALS), Alzheimer's disease, peripheral neuropathy, and other neurodegenerative diseases. In addition, NMNAT2 exerts a cancer-promoting role in solid tumors, including colorectal cancer, lung cancer, ovarian cancer, and glioma, and is closely related to tumor occurrence and development. This paper reviews the chromosomal and subcellular localization of NMNAT2 and its basic biological functions. We also summarize the NMNAT2-related signal transduction pathway and the role of NMNAT2 in diseases. We aimed to provide a new perspective to comprehensively understand the relationship between NMNAT2 and its associated diseases.
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•NMNAT2 is an evolutionarily conserved NAD+ synthase located in the cytoplasm and Golgi apparatus.•NMNAT2 plays an axonal protective role in neurodegenerative diseases by the NMNAT2-NAD+-SARM1 signal axis.•NMNAT2 promotes the occurrence and development of solid tumors.•NMNAT2 is an important molecular target affecting disease treatment.
The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry and the focus for development of protective antibodies and vaccines. Structural studies show ...exposed sites on the spike trimer that might be targeted by antibodies with cross-species specificity. Here we isolated two human monoclonal antibodies from immunized humanized mice that display a remarkable cross-reactivity against distinct spike proteins of betacoronaviruses including SARS-CoV, SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both cross-reactive antibodies target the stem helix in the spike S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle. Both antibodies block MERS-CoV infection in cells and provide protection to mice from lethal MERS-CoV challenge in prophylactic and/or therapeutic models. Our work highlights an immunogenic and vulnerable site on the betacoronavirus spike protein enabling elicitation of antibodies with unusual binding breadth.
Along with the intensification of global ecological problems, corporate environmental, social, and governance (ESG) issues have attracted extensive attention from the investment community, and ...solving these issues is crucial for sustainable development. However, little is known about the research on equity structure reform on corporate ESG performance, especially state-owned capital on private firms' ESG performance. To this end, we utilize the panel data of 1,589 privately listed firms in China from 2013 to 2021 to explore the impact of state-owned capital on the ESG performance of private firms. The findings suggest that state-owned capital significantly improves the ESG performance of private firms. In addition, the results of mechanism analysis indicate that state-owned capital stimulates ESG performance through the dual path of improving the mitigation of external financial constraint problems and internal control environment problems. We also find that firms' external environmental shocks enhance the extent to which state capital injection into private firms enhances ESG performance, and these external environmental shocks include the strength of environmental regulation in the region, whether the firms' attribute is that of heavily polluting industries, and the strength of external media attention. In summary, our findings support the conjecture that state capital injection into private firms will be followed by enhanced ESG performance, and the external environment is a factor that influences this process. Our study may provide lessons for the sustainable development of private firms and dig deeper into the internal root causes and external shock factors.
mRNA vaccines are becoming a feasible alternative for treating cancer. To develop mRNA vaccines against LUAD, potential antigens were identified and LUAD ferroptosis subtypes distinguished for ...selecting appropriate patients. The genome expression omnibus, cancer genome atlas (TCGA) and FerrDB were used to collect gene expression profiles, clinical information, and the genes involved in ferroptosis, respectively. cBioPortal was used to visualize and compare genetic alterations, GEPIA2 to calculate prognostic factors of the selected antigens, and TIMER to visualize the relationship between potential antigens and tumor immune cell infiltration. Consensus clustering analysis was utilized to identify ferroptosis subtypes and their prognostic value assessed by Log-rank and cox regression tests. The modules of ferroptosis-related gene screening were conducted by weight gene co-expression network analysis. The LUAD ferroptosis landscape was visualized through dimensionality reduction and graph learning. Six tumor antigens had obvious LUAD-mutations, positively correlated with different antigen-presenting cells, and might induce tumor cell ferroptosis. LUAD patients were stratified into three ferroptosis subtypes (FS1, FS2, and FS3) according to diverse molecular, cellular, and clinical characteristics. FS3 showed the highest tumor mutation burden and the most somatic mutations, deemed potential indicators of mRNA vaccine effectiveness. Moreover, different ferroptosis subtypes expressed distinct immune checkpoints and immunogenic cell death modulators. AGPS, NRAS, MTDH, PANX1, NOX4, and PPARD are potentially suitable for mRNA vaccinations against LUAD, specifically in patients with FS3 tumors. This study defines vaccination candidates and establishes a theoretical basis for LUAD mRNA vaccinations.
Depression, a common worldwide mental disorder, which brings huge challenges to family and social burden around the world is different from fluctuant emotion and psychological pressure in their daily ...life. Although body signs have been shown to present manifestations of depression in general, few researches focus on whole body kinematic cues with the help of machine learning methods to aid depression recognition. Using the Kinect V2 device to record participants' simple kinematic skeleton data of the participant's body joints, the presented spatial features and low-level features is directly extracted from the record original Kinect-3D coordinates. This research aimed to constructed machine learning model with the preprocessed data importing, which could be used for depression automatic classification.
Considering some patients' conditions and current status and refer to psychiatrists' advices, simple and significant designed stimulus task will lead human skeleton data collection job. With original Kinect skeleton data extracting and preprocessing, the proposed experiment demonstrated four strong machine learning tools: Support Vector Machine, Logistic Regression, Random Forest and Gradient Boosting. Using the precision, recall, sensitivity, specificity, roc-curve, confusion matrix et.al, indicators were calculated as the measurement of methods, which were commonly used to evaluate classification methodologies.
Across screened 64 pairs with age and gender totally matching in depression and control group, and Gradient Boosting achieved the best performance with the prediction accuracy of 76.92%. Sorted by female (54.69%) and male for the gender-based depression recognition, we applied best performance classifier Gradient Boosting got prediction accuracy of 66.67% in the male group, and 71.73% in the female group. Utilizing the best model Gradient Boosting for age-based classification, prediction accuracy got 76.92% in the older group (age >40, 50% of total) and 53.85% accuracy in the younger group (age <= 40).
The depression and non-depression individuals can be well classified by computational models using Kinect captured skeletal data. The Gradient Boosting, an excellent machine learning tool, get the performance in the four methods we demonstrated. Meanwhile, in the gender-based depression classification also gets reasonable accuracy. In particular, the recognition results of the old group are significantly better than that of the young group. All these findings suggest that kinematic skeletal data based depression recognition can be applied as an effective tool for assisting in depression analysis.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cluster of differentiation 38 (CD38) is a cell surface glycoprotein and multifunctional extracellular enzyme. As a NADase, CD38 produces adenosine through the adenosine energy pathway to cause ...immunosuppression. As a cell surface receptor, CD38 is necessary for immune cell activation and proliferation. The aggregation and polarization of macrophages are affected by the knockout of
. Intracellular NAD
levels are reduced by nuclear receptor liver X receptor-alpha (LXR) agonists in a CD38-dependent manner, thereby reducing the infection of macrophages. Previous studies suggested that CD38 plays an important role in the regulation of macrophage function. Therefore, as a new marker of macrophages, the effect of CD38 on macrophage proliferation, polarization and function; its possible mechanism; the relationship between the expression level of CD38 on macrophage surfaces and disease diagnosis, treatment, etc; and the role of targeting CD38 in macrophage-related diseases are reviewed in this paper to provide a theoretical basis for a comprehensive understanding of the relationship between CD38 and macrophages.
Solar irradiation of chlorine-containing waters enhances inactivation of chlorine-resistant pathogens (e.g., Cryptosporidium oocysts), through in situ formation of ozone, hydroxyl radical, and other ...reactive species during photolysis of free available chlorine (FAC) at UVB-UVA wavelengths of solar light (290–400 nm). However, corresponding effects on regulated disinfection byproduct (DBP) formation and associated dissolved organic matter (DOM) properties remain unclear. In this work, when compared to dark chlorination, sunlight-driven FAC photolysis over a range of conditions was found to yield higher DBP levels, depletion of DOM chromophores and fluorophores, preferential removal of phenolic groups versus carboxylic acid groups, and degradation of larger humic substances to smaller molecular weight compounds. Control experiments showed that increased DBP levels were not due to direct DOM photolysis and subsequent dark reactions with FAC, but to co-exposure of DOM to FAC and reactive species (e.g., O3, HO•, Cl•, Cl2•-, ClO•) generated by FAC photolysis. Because solar chlorine photolysis can enable inactivation of chlorine-resistant pathogens at far lower CTFAC values than chlorination alone, the increases in DBP formation inherent to this approach can likely be offset to some extent by the ability to operate at significantly decreased CTFAC. Nonetheless, these findings demonstrate that applications of solar chlorine photolysis will require careful attention to potential impacts on DBP formation.
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•Solar chlorine photolysis increases THM and HAA formation in DOM-containing waters.•DBP formation correlates with extensive photobleaching and decreased MW of DOM.•Photogenerated ROS, RHS, and O3 drive DBP precursor generation and destruction.•THM and HAA levels can be maintained below MCLs in waters with low DOC and bromide.•Use of solar chlorine photolysis for disinfection requires attention to DBP impacts.
An edge displacement sensor is one of the key technologies for building large segmented mirror astronomical optical telescopes. A digital interface is one novel approach for sensor technologies, ...digital transformation and the Internet of Things (IoT) in particular. Frequency output sensors and inductance-to-digital converter (LDC) demonstrated significant advantages in comparison with conventional sensors with analog-to-digital converter (ADC) interfaces. In order for the differential inductive frequency output displacement (DIFOD) sensor to meet the high-stability requirements of segmented mirror astronomical telescopes, it is important to understand the factors for time drift of the sensor. This paper focuses on the investigation of key factors of sensor structure and material, signal conditioning and interface, and fixtures for time drift to permanently installed applications. First, the measurement principle and probe structural characteristics of the sensor are analyzed. Then, two kinds of signal conditioning and digitalization methods using resonance circuits and LDC chips are implemented and compared. Finally, the time drift stability experiments are performed on the sensors with different signal conditioning methods and fixtures under controlled temperature. Experimental results show that the magnetic shield ring effectively improves the sensitivity and quality factor of the sensors, the time drift stability of the sensor using the signal conditioning based on resonance circuits is better than that of the sensors using LDC chips, and the root mean square (RMS) of the sensor time drift meets the requirement of 0.01 μm/24 h. This study will help further development of high-stability of frequency output sensors and IoT-based systems for scaled-up applications in the future.
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