2,559 research outputs found
Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau.
While a number of genome-wide association studies have identified microtubule-associated protein tau as a strong risk factor for Parkinson's disease (PD), little is known about the mechanism through which human tau can predispose an individual to this disease. Here, we demonstrate that expression of human wild-type tau is sufficient to disrupt the survival of dopaminergic neurons in a Drosophila model. Tau triggers a synaptic pathology visualized by vesicular monoamine transporter-pHGFP that precedes both the age-dependent formation of tau-containing neurofibrillary tangle-like pathology and the progressive loss of DA neurons, thereby recapitulating the pathological hallmarks of PD. Flies overexpressing tau also exhibit progressive impairments of both motor and learning behaviors. Surprisingly, contrary to common belief that hyperphosphorylated tau could aggravate toxicity, DA neuron degeneration is alleviated by expressing the modified, hyperphosphorylated tau(E14). Together, these results show that impairment of VMAT-containing synaptic vesicle, released to synapses before overt tauopathy may be the underlying mechanism of tau-associated PD and suggest that correction or prevention of this deficit may be appropriate targets for early therapeutic intervention
Towards Assumption-free Bias Mitigation
Despite the impressive prediction ability, machine learning models show
discrimination towards certain demographics and suffer from unfair prediction
behaviors. To alleviate the discrimination, extensive studies focus on
eliminating the unequal distribution of sensitive attributes via multiple
approaches. However, due to privacy concerns, sensitive attributes are often
either unavailable or missing in real-world scenarios. Therefore, several
existing works alleviate the bias without sensitive attributes. Those studies
face challenges, either in inaccurate predictions of sensitive attributes or
the need to mitigate unequal distribution of manually defined non-sensitive
attributes related to bias. The latter requires strong assumptions about the
correlation between sensitive and non-sensitive attributes. As data
distribution and task goals vary, the strong assumption on non-sensitive
attributes may not be valid and require domain expertise. In this work, we
propose an assumption-free framework to detect the related attributes
automatically by modeling feature interaction for bias mitigation. The proposed
framework aims to mitigate the unfair impact of identified biased feature
interactions. Experimental results on four real-world datasets demonstrate that
our proposed framework can significantly alleviate unfair prediction behaviors
by considering biased feature interactions
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Kinetic study of shock formation and particle acceleration in laser-driven quasi-parallel magnetized collisionless shocks
Clinical significance of erythropoietin receptor expression in oral squamous cell carcinoma
BACKGROUND: Hypoxic tumors are refractory to radiation and chemotherapy. High expression of biomarkers related to hypoxia in head and neck cancer is associated with a poorer prognosis. The present study aimed to evaluate the clinicopathological significance of erythropoietin receptor (EPOR) expression in oral squamous cell carcinoma (OSCC). METHODS: The study included 256 patients who underwent primary surgical resection between October 1996 and August 2005 for treatment of OSCC without previous radiotherapy and/or chemotherapy. Clinicopathological information including gender, age, T classification, N classification, and TNM stage was obtained from clinical records and pathology reports. The mRNA and protein expression levels of EPOR in OSCC specimens were evaluated by Q-RT-PCR, Western blotting and immunohistochemistry assays. RESULTS: We found that EPOR were overexpressed in OSCC tissues. The study included 17 women and 239 men with an average age of 50.9 years (range, 26–87 years). The mean follow-up period was 67 months (range, 2–171 months). High EPOR expression was significantly correlated with advanced T classification (p < 0.001), advanced TNM stage (p < 0.001), and positive N classification (p = 0.001). Furthermore, the univariate analysis revealed that patients with high tumor EPOR expression had a lower 5-year overall survival rate (p = 0.0011) and 5-year disease-specific survival rate (p = 0.0017) than patients who had low tumor levels of EPOR. However, the multivariate analysis using Cox’s regression model revealed that only the T and N classifications were independent prognostic factors for the 5-year overall survival and 5-year disease-specific survival rates. CONCLUSIONS: High EPOR expression in OSCC is associated with an aggressive tumor behavior and poorer prognosis in the univariate analysis among patients with OSCC. Thus, EPOR expression may serve as a treatment target for OSCC in the future
Polymicrobial bloodstream infection involving Aeromonas species: Analysis of 62 cases
AbstractObjectiveTo better understand Aeromonas-involved polymicrobial bacteremia (AIPMB).Materials and MethodsWe conducted a retrospective analysis of patients with AIPMB admitted to three large referral hospitals in Taiwan between 2001 and 2008.ResultsOf a total of 62 patients with AIPMB, 22 had healthcare-associated infection and 40 had community-acquired infection. Enterobacteriaceae was the most common concurrent pathogen (82%). The leading underlying diseases/conditions in the affected patients were solid cancers (45%), recent gastric acid suppressant therapy (39%) and liver cirrhosis (26%). More than 95% of the Aeromonas isolates were susceptible to an aminoglycoside, a third- or fourth-generation cephalosporin, imipenem or ciprofloxacin. Antibiotic susceptibilities did not significantly differ between Aeromonas isolates in patients with healthcare-associated AIPMBs and those in patients with community-acquired AIPMBs. Coinfection with Enterobacteriaceae occurred more commonly in community-acquired AIPMB (93% vs. 64%; p=0.012).ConclusionsAIPMB occurred commonly in patients with liver cirrhosis, solid cancers or recent gastric acid suppressant therapy. Enterobacteriaceae were the most common concurrent pathogens. Similar antibiotic profiles were found in Aeromonas isolates of healthcare-associated and community-acquired AIPMBs
Type-II Topological Dirac Semimetals: Theory and Materials Prediction (VAl3 family)
The discoveries of Dirac and Weyl semimetal states in spin-orbit compounds
led to the realizations of elementary particle analogs in table-top
experiments. In this paper, we propose the concept of a three-dimensional
type-II Dirac fermion and identify a new topological semimetal state in the
large family of transition-metal icosagenides, MA3 (M=V, Nb, Ta; A=Al, Ga, In).
We show that the VAl3 family features a pair of strongly Lorentz-violating
type-II Dirac nodes and that each Dirac node consists of four type-II Weyl
nodes with chiral charge +/-1 via symmetry breaking. Furthermore, we predict
the Landau level spectrum arising from the type-II Dirac fermions in VAl3 that
is distinct from that of known Dirac semimetals. We also show a topological
phase transition from a type-II Dirac semimetal to a quadratic Weyl semimetal
or a topological crystalline insulator via crystalline distortions. The new
type-II Dirac fermions, their novel magneto-transport response, the topological
tunability and the large number of compounds make VAl3 an exciting platform to
explore the wide-ranging topological phenomena associated with
Lorentz-violating Dirac fermions in electrical and optical transport,
spectroscopic and device-based experiments.Comment: 28 pages, 7 Figure
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