273 research outputs found
Biomechanical evaluation of three surgical scenarios of posterior lumbar interbody fusion by finite element analysis
BACKGROUND: For the treatment of low back pain, the following three scenarios of posterior lumbar interbody fusion (PLIF) were usually used, i.e., PLIF procedure with autogenous iliac bone (PAIB model), PLIF with cages made of PEEK (PCP model) or titanium (Ti) (PCT model) materiel. But the benefits or adverse effects among the three surgical scenarios were still not fully understood. METHOD: Finite element analysis (FEA), as an efficient tool for the analysis of lumbar diseases, was used to establish a three-dimensional nonlinear L1-S1 FE model (intact model) with the ligaments of solid elements. Then it was modified to simulate the three scenarios of PLIF. 10 Nm moments with 400 N preload were applied to the upper L1 vertebral body under the loading conditions of extension, flexion, lateral bending and torsion, respectively. RESULTS: Different mechanical parameters were calculated to evaluate the differences among the three surgical models. The lowest stresses on the bone grafts and the greatest stresses on endplate were found in the PCT model. The PCP model obtained considerable stresses on the bone grafts and less stresses on ligaments. But the changes of stresses on the adjacent discs and endplate were minimal in the PAIB model. CONCLUSIONS: The PCT model was inferior to the other two models. Both the PCP and PAIB models had their own relative merits. The findings provide theoretical basis for the choice of a suitable surgical scenario for different patients
Weak Collocation Regression for Inferring Stochastic Dynamics with L\'{e}vy Noise
With the rapid increase of observational, experimental and simulated data for
stochastic systems, tremendous efforts have been devoted to identifying
governing laws underlying the evolution of these systems. Despite the broad
applications of non-Gaussian fluctuations in numerous physical phenomena, the
data-driven approaches to extracting stochastic dynamics with L\'{e}vy noise
are relatively few. In this work, we propose a Weak Collocation Regression
(WCR) to explicitly reveal unknown stochastic dynamical systems, i.e., the
Stochastic Differential Equation (SDE) with both -stable L\'{e}vy noise
and Gaussian noise, from discrete aggregate data. This method utilizes the
evolution equation of the probability distribution function, i.e., the
Fokker-Planck (FP) equation. With the weak form of the FP equation, the WCR
constructs a linear system of unknown parameters where all integrals are
evaluated by Monte Carlo method with the observations. Then, the unknown
parameters are obtained by a sparse linear regression. For a SDE with L\'{e}vy
noise, the corresponding FP equation is a partial integro-differential equation
(PIDE), which contains nonlocal terms, and is difficult to deal with. The weak
form can avoid complicated multiple integrals. Our approach can simultaneously
distinguish mixed noise types, even in multi-dimensional problems. Numerical
experiments demonstrate that our method is accurate and computationally
efficient.Comment: 19 pages, 5 figures, 10 table
The relationship between BSP mRNA expression and 25(OH)D/OPG in peripheral blood of newly diagnosed T2DM patients with different bone mass
Introduction: The objective of the study was to detect the levels of osteoprotegerin (OPG) and 25-hydroxyvitamin D [25(OH)D], as well as the expression of bone sialoprotein (BSP) mRNA, in the peripheral blood of patients with newly diagnosed type 2 diabetes mellitus (T2DM) under different bone mass conditions, and to explore its role and significance in the development process of T2DM combined with osteoporosis (OP). Material and methods: A total of 225 patients hospitalised in the Endocrinology Department and General Department from May 2017 to May 2018 were enrolled and categorised into five groups: the pure T2DM group (group A, 45 patients), the bone mass reduction group (group B, 45 patients), the T2DM + bone mass reduction group (group C, 45 patients), the OP group (group D, 45 patients), and the T2DM + OP group (group E, 45 patients); meanwhile, age-matched healthy subjects undergoing physical examination in our hospital were collected as the normal control group (group NC, 45 cases). Logistic regression analysis was used to analyse the influencing factors of bone mass in patients with T2DM. Results: Compared with group B, the expression levels of glycated haemoglobin (HbA1c), 25(OH)D, N-terminal propeptide of type I procollagen (PINP), fasting plasma glucose (FPG), fasting plasma insulin (FINS), high-density lipoprotein cholesterol (HDL-C), and BSP mRNA were significantly increased while OPG and b-collagen degradation products (b-CTX) were significantly decreased in group A. Conclusion: The expression of BSP mRNA and the decrease of 25(OH)D and OPG in peripheral blood may participate in the development of diabetes and osteoporosis
A Single {frame}
1 volume, 6 pages. Numbered edition of 12 copies. printed in Caslon Old Style on French paper with watercolor and lino-cuts --colophon. .. [Produced] spring 2019 [for] Art 136: The Artist\u27s Book course, taught by Tia Blassingame --colophon. Combines handset letterpress, linocuts, watercolor, papercutting and an interactive element to express the significance of self. --Scripts Press.https://digitalcommons.risd.edu/specialcollections_artistsbooks/1194/thumbnail.jp
The Janus Interface: How Fine-Tuning in Large Language Models Amplifies the Privacy Risks
The era post-2018 marked the advent of Large Language Models (LLMs), with
innovations such as OpenAI's ChatGPT showcasing prodigious linguistic prowess.
As the industry galloped toward augmenting model parameters and capitalizing on
vast swaths of human language data, security and privacy challenges also
emerged. Foremost among these is the potential inadvertent accrual of Personal
Identifiable Information (PII) during web-based data acquisition, posing risks
of unintended PII disclosure. While strategies like RLHF during training and
Catastrophic Forgetting have been marshaled to control the risk of privacy
infringements, recent advancements in LLMs, epitomized by OpenAI's fine-tuning
interface for GPT-3.5, have reignited concerns. One may ask: can the
fine-tuning of LLMs precipitate the leakage of personal information embedded
within training datasets? This paper reports the first endeavor to seek the
answer to the question, particularly our discovery of a new LLM exploitation
avenue, called the Janus attack. In the attack, one can construct a PII
association task, whereby an LLM is fine-tuned using a minuscule PII dataset,
to potentially reinstate and reveal concealed PIIs. Our findings indicate that,
with a trivial fine-tuning outlay, LLMs such as GPT-3.5 can transition from
being impermeable to PII extraction to a state where they divulge a substantial
proportion of concealed PII. This research, through its deep dive into the
Janus attack vector, underscores the imperative of navigating the intricate
interplay between LLM utility and privacy preservation
Physical activity improves the visual–spatial working memory of individuals with mild cognitive impairment or Alzheimer’s disease: a systematic review and network meta-analysis
ObjectiveOur network meta-analysis aimed to ascertain the effect of physical activity on the visual–spatial working memory of individuals with mild cognitive impairment and Alzheimer’s disease as well as to propose tailored exercise interventions for each group.MethodsEmploying a frequentist approach, we performed a network meta-analysis to compare the effectiveness of different exercise interventions in improving the visual–spatial working memory of individuals with mild cognitive impairment and Alzheimer’s disease. Subsequently, we explored the moderating variables influencing the effectiveness of the exercise interventions through a subgroup analysis.ResultsWe included 34 articles involving 3,074 participants in the meta-analysis, comprised of 1,537 participants from studies on mild cognitive impairment and 1,537 participants from studies on Alzheimer’s disease. The articles included exhibited an average quality score of 6.6 (score studies) and 6.75 (reaction time [RT] studies), all passing the inconsistency test (p > 0.05). In the mild cognitive impairment literature, mind–body exercise emerged as the most effective exercise intervention (SMD = 0.61, 95% CI: 0.07–1.14). In Alzheimer’s disease research, aerobic exercise was identified as the optimal exercise intervention (SMD = 0.39, 95% CI: 0.06–0.71).ConclusionThe results of the subgroup analysis suggest that the most effective approach to enhancing the visual–spatial working memory of individuals with mild cognitive impairment entails exercising at a frequency of three or more times per week for over 60 min each time and at a moderate intensity for more than 3 months. Suitable exercise options include mind–body exercise, multicomponent exercise, resistance exercise, and aerobic exercise. For individuals with Alzheimer’s disease, we recommend moderately intense exercise twice per week for over 90 min per session and for a duration of 3 months or longer, with exercise options encompassing aerobic exercise and resistance exercise
Exosomal cell-to-cell transmission of alpha synuclein oligomers
Background: Aggregation of alpha-synuclein (αsyn) and resulting cytotoxicity is a hallmark of sporadic and familial Parkinson’s disease (PD) as well as dementia with Lewy bodies, with recent evidence implicating oligomeric and pre-fibrillar forms of αsyn as the pathogenic species. Recent in vitro studies support the idea of transcellular spread of extracellular, secreted αsyn across membranes. The aim of this study is to characterize the transcellular spread of αsyn oligomers and determine their extracellular location. Results: Using a novel protein fragment complementation assay where αsyn is fused to non-bioluminescent amino-or carboxy-terminus fragments of humanized Gaussia Luciferase we demonstrate here that αsyn oligomers can be found in at least two extracellular fractions: either associated with exosomes or free. Exosome-associated αsyn oligomers are more likely to be taken up by recipient cells and can induce more toxicity compared to free αsyn oligomers. Specifically, we determine that αsyn oligomers are present on both the outside as well as inside of exosomes. Notably, the pathway of secretion of αsyn oligomers is strongly influenced by autophagic activity. Conclusions: Our data suggest that αsyn may be secreted via different secretory pathways. We hypothesize that exosome-mediated release of αsyn oligomers is a mechanism whereby cells clear toxic αsyn oligomers when autophagic mechanisms fail to be sufficient. Preventing the early events in αsyn exosomal release and uptake by inducing autophagy may be a novel approach to halt disease spreading in PD and other synucleinopathies
Recommended from our members
Direct detection of alpha synuclein oligomers in vivo
Background: Rat models of Parkinson’s disease are widely used to elucidate the mechanisms underlying disease etiology or to investigate therapeutic approaches. Models were developed using toxins such as MPTP or 6-OHDA to specifically target dopaminergic neurons resulting in acute neuronal loss in the substantia nigra or by using viral vectors to induce the specific and gradual expression of alpha synuclein in the substantia nigra. The detection of alpha- synuclein oligomers, the presumed toxic species, in these models and others has been possible using only indirect biochemical approaches to date. Here we coinjected AAVs encoding alpha-synuclein fused to the N- or C-terminal half of VenusYFP in rat substantia nigra pars compacta and describe for the first time a novel viral vector rodent model with the unique ability to directly detect and track alpha synuclein oligomers ex vivo and in vivo. Results: Viral coinjection resulted in widespread VenusYFP signal within the nigrostriatal pathway, including cell bodies in the substantia nigra and synaptic accumulation in striatal terminals, suggestive of in vivo alpha-synuclein oligomers formation. Transduced rats showed alpha-synuclein induced dopaminergic neuron loss in the substantia nigra, the appearance of dystrophic neurites, and gliosis in the striatum. Moreover, we have applied in vivo imaging techniques in the living mouse to directly image alpha-synuclein oligomers in the cortex. Conclusion: We have developed a unique animal model that provides a tool for the Parkinson’s disease research community with which to directly detect alpha- synuclein oligomers in vivo and screen therapeutic approaches targeting alpha-synuclein oligomers
Identification and Characterization of \u3cem\u3eOGG1\u3c/em\u3e Mutations in Patients with Alzheimer\u27s Disease
Patients with Alzheimer\u27s disease (AD) exhibit higher levels of 8-oxo-guanine (8-oxoG) DNA lesions in their brain, suggesting a reduced or defective 8-oxoG repair. To test this hypothesis, this study investigated 14 AD patients and 10 age-matched controls for mutations of the major 8-oxoG removal gene OGG1. Whereas no alterations were detected in any control samples, four AD patients exhibited mutations in OGG1, two carried a common single base (C796) deletion that alters the carboxyl terminal sequence of OGG1, and the other two had nucleotide alterations leading to single amino acid substitutions. In vitro biochemical assays revealed that the protein encoded by the C796-deleted OGG1 completely lost its 8-oxoG glycosylase activity, and that the two single residue-substituted OGG1 proteins showed a significant reduction in the glycosylase activity. These results were consistent with the fact that nuclear extracts derived from a limited number of AD patients with OGG1 mutations exhibited greatly reduced 8-oxoG glycosylase activity compared with age-matched controls and AD patients without OGG1 alterations. Our findings suggest that defects in OGG1 may be important in the pathogenesis of AD in a significant fraction of AD patients and provide new insight into the molecular basis for the disease
- …