New records of florivory on dipterocarp flowers

Peer reviewedPreprin

Socioeconomic determinants of multimorbidity: a population-based household survey of Hong Kong Chinese

<b>Introduction</b> Multimorbidity has been well researched in terms of consequences and healthcare implications. Nevertheless, its risk factors and determinants, especially in the Asian context, remain understudied. We tested the hypothesis of a negative relationship between socioeconomic status and multimorbidity, with contextually different patterns from those observed in the West.<p></p> <b>Methods</b> We conducted our study in the general Hong Kong (HK) population. Data on current health conditions, health behaviours, socio-demographic and socioeconomic characteristics was obtained from HK Government’s Thematic Household Survey. 25,780 individuals aged 15 or above were sampled. Binary logistic and negative binomial regression analyses were conducted to identify risk factors for presence of multimorbidity and number of chronic conditions, respectively. Sub-analysis of possible mediation effect through financial burden borne by private housing residents on multimorbidity was also conducted.<p></p> <b>Results</b> Unadjusted and adjusted models showed that being female, being 25 years or above, having an education level of primary schooling or below, having less than HK$15,000 monthly household income, being jobless or retired, and being past daily smoker were significant risk factors for the presence of multimorbidity and increased number of chronic diseases. Living in private housing was significantly associated with higher chance of multimorbidity and increased number of chronic diseases only after adjustments.<p></p> <b>Conclusions</b>Less advantaged people tend to have higher risks of multimorbidity and utilize healthcare from the public sector with poorer primary healthcare experience. Moreover, middle-class people who are not eligible for government subsidized public housing may be of higher risk of multimorbidity due to psychosocial stress from paying for the severely unaffordable private housing

Molecular mechanisms of amyotrophic lateral sclerosis as broad therapeutic targets for gene therapy applications utilizing adeno-associated viral vectors

Despite the devastating clinical outcome of the neurodegenerative disease, amyotrophic lateral sclerosis (ALS), its etiology remains mysterious. Approximately 90% of ALS is characterized as sporadic, signifying that the patient has no family history of the disease. The development of an impactful disease modifying therapy across the ALS spectrum has remained out of grasp, largely due to the poorly understood mechanisms of disease onset and progression. Currently, ALS is invariably fatal and rapidly progressive. It is hypothesized that multiple factors can lead to the development of ALS, however, treatments are often focused on targeting specific familial forms of the disease (10% of total cases). There is a strong need to develop disease modifying treatments for ALS that can be effective across the full ALS spectrum of familial and sporadic cases. Although the onset of disease varies significantly between patients, there are general disease mechanisms and progressions that can be seen broadly across ALS patients. Therefore, this review explores the targeting of these widespread disease mechanisms as possible areas for therapeutic intervention to treat ALS broadly. In particular, this review will focus on targeting mechanisms of defective protein homeostasis and RNA processing, which are both increasingly recognized as design principles of ALS pathogenesis. Additionally, this review will explore the benefits of gene therapy as an approach to treating ALS, specifically focusing on the use of adeno-associated virus (AAV) as a vector for gene delivery to the CNS and recent advances in the field

Learning to identify contrast-defined letters in peripheral vision

AbstractPerformance for identifying luminance-defined letters in peripheral vision improves with training. The purpose of the present study was to examine whether performance for identifying contrast-defined letters also improves with training in peripheral vision, and whether any improvement transfers to luminance-defined letters. Eight observers were trained to identify contrast-defined letters presented singly at 10° eccentricity in the inferior visual field. Before and after training, we measured observers’ thresholds for identifying luminance-defined and contrast-defined letters, embedded within a field of white luminance noise (maximum luminance contrast=0, 0.25, and 0.5), at the same eccentric location. Each training session consisted of 10 blocks (100 trials per block) of identifying contrast-defined letters at a background noise contrast of 0.5. Letters (x-height=4.2°) were the 26 lowercase letters of the Times-Roman alphabet. Luminance-defined letters were generated by introducing a luminance difference between the stimulus letter and its mid-gray background. The background noise covered both the letter and its background. Contrast-defined letters were generated by introducing a differential noise contrast between the group of pixels that made up the stimulus letter and the group of pixels that made up the background. Following training, observers showed a significant reduction in threshold for identifying contrast-defined letters (p<0.0001). Averaged across observers and background noise contrasts, the reduction was 25.8%, with the greatest reduction (32%) occurring at the trained background noise contrast. There was virtually no transfer of improvement to luminance-defined letters, or to an untrained letter size (2× original), or an untrained retinal location (10° superior field). In contrast, learning transferred completely to the untrained contralateral eye. Our results show that training improves performance for identifying contrast-defined letters in peripheral vision. This perceptual learning effect seems to be stimulus-specific, as it shows no transfer to the identification of luminance-defined letters. The complete interocular transfer, and the retinotopic (retinal location) and size specificity of the learning effect are consistent with the properties of neurons in early visual area V2

Prolonged Aβ treatment leads to impairment in the ability of primary cortical neurons to maintain K+ and Ca2+ homeostasis

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterised by the formation of insoluble amyloidogenic plaques and neurofibrillary tangles. Beta amyloid (Aβ) peptide is one of the main constituents in Aβ plaques, and is thought to be a primary causative agent in AD. Neurons are likely to be exposed to chronic, sublethal doses of Aβ over an extended time during the pathogenesis of AD, however most studies published to date using <it>in vitro </it>models have focussed on acute studies. To experimentally model the progressive pathogenesis of AD, we exposed primary cortical neurons daily to 1 μM of Aβ_1-40over 7 days and compared their survival with age-similar untreated cells. We also investigated whether chronic Aβ exposure affects neuronal susceptibility to the subsequent acute excitotoxicity induced by 10 μM glutamate and assessed how Ca²⁺and K⁺homeostasis were affected by either treatment.</p> <p>Results</p> <p>We show that continuous exposure to 1 μM Aβ_1-40for seven days decreased survival of cultured cortical neurons by 20%. This decrease in survival correlated with increased K⁺efflux from the cells. One day treatment with 1 μM Aβ followed by glutamate led to a substantially higher K⁺efflux than in the age-similar untreated control. This difference further increased with the duration of the treatment. K⁺efflux also remained higher in Aβ treated cells 20 min after glutamate application leading to 2.8-fold higher total K⁺effluxed from the cells compared to controls. Ca²⁺uptake was significantly higher only after prolonged Aβ treatment with 2.5-fold increase in total Ca²⁺uptake over 20 min post glutamate application after six days of Aβ treatment or longer (P < 0.05).</p> <p>Conclusions</p> <p>Our data suggest that long term exposure to Aβ is detrimental because it reduces the ability of cortical neurons to maintain K⁺and Ca²⁺homeostasis in response to glutamate challenge, a response that might underlie the early symptoms of AD. The observed inability to maintain K⁺homeostasis might furthermore be useful in future studies as an early indicator of pathological changes in response to Aβ.</p

Training strategy for a lightweight countermeasure model for automatic speaker verification

The countermeasure (CM) model is developed to protect Automatic Speaker Verification (ASV) systems from spoof attacks and prevent resulting personal information leakage. Based on practicality and security considerations, the CM model is usually deployed on edge devices, which have more limited computing resources and storage space than cloud-based systems. This work proposes training strategies for a lightweight CM model for ASV, using generalized end-to-end (GE2E) pre-training and adversarial fine-tuning to improve performance, and applying knowledge distillation (KD) to reduce the size of the CM model. In the evaluation phase of the ASVspoof 2021 Logical Access task, the lightweight ResNetSE model reaches min t-DCF 0.2695 and EER 3.54%. Compared to the teacher model, the lightweight student model only uses 22.5% of parameters and 21.1% of multiply and accumulate operands of the teacher model.Comment: ASVspoof202

A quantitative microfluidic angiogenesis screen for studying anti-angiogenic therapeutic drugs

Anti-angiogenic therapy, which suppresses tumor growth by disrupting oxygen and nutrient supply from blood to the tumor, is now widely accepted as a treatment for cancer. To investigate the mechanisms of action of these anti-angiogenesis drugs, new three dimensional (3D) cell culture-based drug screening models are increasingly employed. However, there is no in vitro high-throughput screening (HTS) angiogenesis assay that can provide uniform culture conditions for the quantitative assessment of physiological responses to chemoattractant reagents under various concentrations of anti-angiogenesis drugs. Here we describe a method for screening and quantifying the vascular endothelial growth factor (VEGF)-induced chemotactic response on human umbilical vein endothelial cells (HUVECs) cultured with different concentrations of bortezomib, a selective 26S proteasome inhibitor. With this quantitative microfluidic angiogenesis screen (QMAS), we demonstrate that bortezomib-induced endothelial cell death is preceded by a series of morphological changes that develop over several days. We also explore the mechanisms by which bortezomib can inhibit angiogenesis.National Institutes of Health (U.S.) (R33 CA174550)National Science Foundation (U.S.) (CBET-0939511)National Research Foundation of Korea (Pioneer Research Center Program 2012-0009565 and 2014M3A7B4052193)Korea (South). Sanggong Chawŏnbu (No. 2012401020325