Background: Biomarkers for neurodegenerative diseases are essential to facilitate disease diagnosis. Application of proteomics has greatly hastened the search for novel biomarkers. In this study, new potential biomarkers were discovered, and a diagnostic pattern was established for idiopathic Parkinson’s disease (PD) by using proteomic technology. Methods: Serum proteins from PD patients and controls were captured by magnetic bead-based weak cation exchange. The molecular weight of the proteins in bead-binding fraction was detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Biomarker Wizard 3.1 and Biomarker Patterns Software were used for data analysis and constructing a model of biomarkers. A blinded testing set was used to validate the model. Results: A total of 17 discriminating m/z peaks related to PD were identified. The model based on the 5 biomarkers generated an excellent separation between PD and healthy controls with 98.36% for the sensitivity and 83.05% for the specificity. Blind test data demonstrated the model could recognize patients with PD with a sensitivity of 85.0% and a specificity of 70.0%. Conclusions: The preliminary data suggested a potential application of MALDI-TOF-MS combined with magnetic beads. The model comprising 5 promising biomarkers can differentiate individuals with PD and the healthy subjects precisely.
Untreated invasive fungal infection is one of the important risk factors affecting the prognosis of pediatric patients with hematologic tumors. Voriconazole (VOR) is the first‐line antifungal drug for the treatment of Aspergillus infections. In order to reduce the risk of adverse drug reactions while producing an ideal antifungal effect, therapeutic drug monitoring was performed to maintain the VOR plasma concentration in a range of 1,000–5,500 ng/ml. In the present study, a reliable, accurate, sensitive and quick ultra‐high performance liquid chromatograph–tandem mass spectrometry (UPLC–MS/MS) method was developed for the determination of the VOR level. Protein precipitation was performed using acetonitrile, and then the chromatographic separation was carried out by UPLC using a C18 column with the gradient mobile phases comprising 0.1% methanoic acid in acetonitrile (A) and 0.1% methanoic acid in water (B). In the selective reaction monitor mode, the mass spectrometric detection was carried out using an TSQ Endura triple quadruple mass spectrometer. The performance of this UPLC–MS/MS method was validated as per the National Medical Products Administration for Bioanalytical Method Validation. Additionally, the plasma concentrations of VOR in pediatric patients with hematologic tumors were detected using this method, and the analyzed results were used for personalized therapy.
Internet is composed of thousands of autonomous systems (AS). The Border Gateway Protocol (BGP) is the exterior routing protocol used to exchange network reachability information between border routers of each AS. The correctness of the exchanged information in BGP messages is crucial to the Internet routing system. Unfortunately, BGP is vulnerable to different attacks that have considerable impacts on routing system. Network prefix hijacking, where an AS illegitimately originates a prefix is one of the most important attacks. It allows the attacker to receive traffic in destination to the prefix owner. The attacker is then able to blackhole the traffic or to force it to take another path. Proposed solutions rely on public key infrastructures and cryptographic mechanisms to prevent incorrect routing information propagation. In practice these approaches involve many parties (Internet Service Providers, Operators, Vendors, and Regional Internet Registries) and are difficult to deploy. In this paper we formally define routing information correctness, especially the legitimacy of an AS to originate a prefix. We also propose a method to associate with an AS a legitimacy level to originate a prefix. We use Regional Internet Registry databases to initialize the legitimacy level. We also use received announcements and public routing data to update this legitimacy level. We finally describe all conceivable reactions facing origin AS changes.
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