237 research outputs found
A Validation Approach to Over-parameterized Matrix and Image Recovery
In this paper, we study the problem of recovering a low-rank matrix from a
number of noisy random linear measurements. We consider the setting where the
rank of the ground-truth matrix is unknown a prior and use an overspecified
factored representation of the matrix variable, where the global optimal
solutions overfit and do not correspond to the underlying ground-truth. We then
solve the associated nonconvex problem using gradient descent with small random
initialization. We show that as long as the measurement operators satisfy the
restricted isometry property (RIP) with its rank parameter scaling with the
rank of ground-truth matrix rather than scaling with the overspecified matrix
variable, gradient descent iterations are on a particular trajectory towards
the ground-truth matrix and achieve nearly information-theoretically optimal
recovery when stop appropriately. We then propose an efficient early stopping
strategy based on the common hold-out method and show that it detects nearly
optimal estimator provably. Moreover, experiments show that the proposed
validation approach can also be efficiently used for image restoration with
deep image prior which over-parameterizes an image with a deep network.Comment: 29 pages and 9 figure
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Immediate Antiretroviral Therapy Decreases Mortality Among Patients With High CD4 Counts in China: A Nationwide, Retrospective Cohort Study.
BackgroundClinical trials have demonstrated that immediate initiation of antiretroviral therapy (ART) reduces AIDS-related morbidity and mortality. We tested the hypothesis that initiating ART ≤30 days after human immunodeficiency virus (HIV) diagnosis would be associated with reduced mortality among people living with HIV (PLWH) with CD4 counts >500 cells/μL.MethodsPLWH enrolled in the Chinese National HIV Information System between January 2012 and June 2014 with CD4 counts >500 cells/μL were followed for 12 months. Cox proportional hazards model was used to determine hazard ratios (HRs) for PLWH who initiated ART after HIV diagnosis. ART initiation was treated as a time-dependent variable.ResultsWe enrolled 34581 PLWH with CD4 >500 cells/μL; 1838 (5.3%) initiated ART ≤30 days after diagnosis (immediate ART group), and 19 deaths were observed with a mortality rate of 1.04 per 100 person-years (PY). Fifty-eight deaths were documented among the 5640 PLWH in the delayed ART group with a mortality rate of 2.25 per 100 PY. There were 713 deaths among the 27103 PLWH in the no ART group with a mortality rate of 2.39 per 100 PY. After controlling for potential confounding factors, ART initiation at ≤30 days (adjusted HR, 0.37 [95% confidence interval, .23-.58]) was a statistically significant protective factor.ConclusionsWe found that immediate ART is associated with a 63% reduction in overall mortality among PLWH with CD4 counts >500 cells/μL in China, supporting the recommendation to initiate ART immediately following HIV diagnosis
Design and Synthesis of Neuroprotective Methylthiazoles and Modification as NO-Chimeras for Neurodegenerative Therapy
Learning and memory deficits in Alzheimer’s disease (AD) result from synaptic failure and neuronal loss, the latter caused in part by excitotoxicity and oxidative stress. A therapeutic approach is described that uses NO-chimeras directed at restoration of both synaptic function and neuroprotection. 4-Methylthiazole (MZ) derivatives were synthesized, based upon a lead neuroprotective pharmacophore acting in part by GABAA receptor potentiation. MZ derivatives were assayed for protection of primary neurons against oxygen−glucose deprivation and excitotoxicity. Selected neuroprotective derivatives were incorporated into NO-chimera prodrugs, coined nomethiazoles. To provide proof of concept for the nomethiazole drug class, selected examples were assayed for restoration of synaptic function in hippocampal slices from AD-transgenic mice, reversal of cognitive deficits, and brain bioavailability of the prodrug and its neuroprotective MZ metabolite. Taken together, the assay data suggest that these chimeric nomethiazoles may be of use in treatment of multiple components of neurodegenerative disorders, such as AD
Two-dimensional germanium islands with Dirac signature on Ag2Ge surface alloy
Two-dimensional (2D) Dirac materials have attracted intense research efforts
due to their promise for applications ranging from field-effect transistors and
low-power electronics to fault-tolerant quantum computation. One key challenge
is to fabricate 2D Dirac materials hosting Dirac electrons. Here, monolayer
germanene is successfully fabricated on a Ag2Ge surface alloy. Scanning
tunneling spectroscopy measurements revealed a linear energy dispersion
relation. The latter was supported by density functional theory calculations.
These results demonstrate that monolayer germanene can be realistically
fabricated on a Ag2Ge surface alloy. The finding opens the door to exploration
and study of 2D Dirac material physics and device applications
Association of Aβ with Ceramide-Enriched Astrosomes Mediates Aβ Neurotoxicity
Amyloid-β (Aβ) associates with extracellular vesicles termed exosomes. It is not clear whether and how exosomes modulate Aβ neurotoxicity in Alzheimer\u27s disease (AD). We show here that brain tissue and serum from the transgenic mouse model of familial AD (5xFAD) and serum from AD patients contains ceramide-enriched and astrocyte-derived exosomes (termed astrosomes) that are associated with Aβ. In Neuro-2a cells, primary cultured neurons, and human induced pluripotent stem cell-derived neurons, Aβ-associated astrosomes from 5xFAD mice and AD patient serum were specifically transported to mitochondria, induced mitochondrial clustering, and upregulated the fission protein Drp-1 at a concentration corresponding to 5 femtomoles Aβ/L of medium. Aβ-associated astrosomes, but not wild type or control human serum exosomes, mediated binding of Aβ to voltage-dependent anion channel 1 (VDAC1) and subsequently, activated caspases. Aβ-associated astrosomes induced neurite fragmentation and neuronal cell death, suggesting that association with astrosomes substantially enhances Aβ neurotoxicity in AD and may comprise a novel target for therapy
Failure of early mycological clearance in HIV-negative cryptococcal meningitis
BACKGROUND: Negative cerebrospinal fluid (CSF) cultures at 2 weeks after antifungal treatment (early mycological clearance [EMC]) should be a treatment goal of cryptococcal meningitis (CM). However, EMC in human immunodeficiency virus (HIV)-negative patients with CM is poorly understood.
METHODS: We conducted a retrospective review of medical records and 1-year follow-up of 141 HIV-negative patients with CM with an initial positive CSF culture for
RESULTS: Of 141 patients, 28 (19.9%) had EMC failure. The 1-year mortality rate was 5.7% (8/141). Multivariate analysis showed that non-amphotericin B (AmB)-based regimens, baseline log
CONCLUSIONS: EMC failure in HIV-negative CM is attributed to non-AmB-based therapy and is associated with lo
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