rMAPS: RNA map analysis and plotting server for alternative exon regulation.

RNA-binding proteins (RBPs) play a critical role in the regulation of alternative splicing (AS), a prevalent mechanism for generating transcriptomic and proteomic diversity in eukaryotic cells. Studies have shown that AS can be regulated by RBPs in a binding-site-position dependent manner. Depending on where RBPs bind, splicing of an alternative exon can be enhanced or suppressed. Therefore, spatial analyses of RBP motifs and binding sites around alternative exons will help elucidate splicing regulation by RBPs. The development of high-throughput sequencing technologies has allowed transcriptome-wide analyses of AS and RBP-RNA interactions. Given a set of differentially regulated alternative exons obtained from RNA sequencing (RNA-seq) experiments, the rMAPS web server (http://rmaps.cecsresearch.org) performs motif analyses of RBPs in the vicinity of alternatively spliced exons and creates RNA maps that depict the spatial patterns of RBP motifs. Similarly, rMAPS can also perform spatial analyses of RBP-RNA binding sites identified by cross-linking immunoprecipitation sequencing (CLIP-seq) experiments. We anticipate rMAPS will be a useful tool for elucidating RBP regulation of alternative exon splicing using high-throughput sequencing data

The Minnesota Haptic Function Test

Haptic loss severely compromises the fine motor control of many daily manual tasks. Today, no widely accepted assessment protocols of haptic function are in clinical use. This is primarily due to the scarcity of fast, objective measures capable of characterizing mild to severe forms of haptic dysfunction with appropriate resolution. This study introduces a novel curvature-perception assessment system called the Minnesota Haptic Function Test™ that seeks to overcome the shortcomings of current clinical assessments.Aims: The purpose of this study was threefold: (1) apply the test to a sample of young healthy adults to establish test-specific adult norms for haptic sensitivity and acuity; (2) establish the reliability of this instrument; (3) demonstrate clinical efficacy in a limited sample of cancer survivors who may exhibit haptic dysfunction due to chemotherapy-induced peripheral neuropathy.Method: Participants manually explored two curved surfaces successively and made verbal judgments about their curvature. A Bayesian-based adaptive algorithm selected presented stimulus pairs based on a subject’s previous responses, which ensured fast convergence toward a threshold. Haptic sensitivity was assessed by obtaining detection thresholds in 26 adults (19–34 years). Haptic acuity was assessed by obtaining just-noticeable-difference thresholds in a second sample of 28 adults (19–25 years). Nine cancer survivors (18–25 years) with suspected peripheral neuropathy completed the acuity assessment. Test-retest reliability of the algorithm was calculated.Results: First, the test yielded values that are consistent with those reported in the literature. Mean detection threshold for curvature of the healthy adults was 0.782 (SD ± 0.320 m−1). The corresponding mean discrimination threshold was 1.030 (SD ± 0.462 m−1). Second, test-retest reliability of the algorithm was assessed in a simulation, yielding an average correlation between repeated simulated thresholds of r = 0.93. Third, the test documented that 86% of the cancer survivors had acuity thresholds above the 75th percentile of the normative cohort, and 29% had thresholds above the normal range, indicating that the instrument can detect and differentiate between unaffected perception, and mild or more severe forms of haptic loss.Conclusion: We here provide evidence that this new method to assess haptic perception of curvature is valid, reliable, and clinically practicable

Neuroprotective Effects of San-Huang-Xie-Xin-Tang in the MPP+/MPTP Models of Parkinson's Disease In Vitro and In Vivo

San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix, and Rhei rhizoma, is a traditional Chinese medicine used for complementary and alternative therapy of cardiovascular and neurodegenerative diseases via its anti-inflammatory and antioxidative effects. The aim of this study is to investigate the protective effects of SHXT in the 1–methyl–4–phenylpyridinium (MPP+)/1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP) models of Parkinson's disease. Rat primary mesencephalic neurons and mouse Parkinson disease model were used in this study. Oxidative stress was induced by MPP+ in vitro and MPTP in vivo. In MPP+-treated mesencephalic neuron cultures, SHXT significantly increased the numbers of TH-positive neurons. SHXT reduced apoptotic signals (cytochrome and caspase) and apoptotic death. MPP+-induced gp91phox activation and ROS production were attenuated by SHXT. In addition, SHXT increased the levels of GSH and SOD in MPP+-treated neurons. In MPTP animal model, SHXT markedly increased TH-positive neurons in the substantia nigra pars compacta (SNpc) and improved motor activity of mice. In conclusion, the present results reveal the evidence that SHXT possesses beneficial protection against MPTP-induced neurotoxicity in this model of Parkinson's disease via its antioxidative and antiapoptotic effects. SHXT might be a potentially alternative and complementary medicine for neuroprotection

說圖──崇禎本《金瓶梅》繡像研究

[[abstract]]　　小說繡像的出現原本只是做為書坊銷售手法，然而文字與圖像的表現特性不同，使繡像極可能是含讀者意識的再創作。《金瓶梅》小說本身的風月筆墨、大量窺視場景，以及人物語言和市井主題都造就了作畫之難度，崇禎本《金瓶梅》繡像卻能嘗試突破困難，以大量留白和多變視角、新增窺視人物等，展現畫工閱讀態度，並帶領讀者領會隱藏主旨。繡像因此隱含畫工的道德及審美判斷等讀者意識，具備了評點性質，在諸家評點外，提供另一種形式的觀看角度與閱讀態度。本論文因此以繡像主要限制條件「回目」作為主要分界，討論崇禎本《金瓶梅》繡像於回目之內的詮釋，甚至不惜突破回目限制的再創造。藉此論證畫工是否是聰明的讀者，若是，其觀點與同行的崇禎本評點，甚至其後的張竹坡、文龍評點，是否有異同之處，藉此論證繡像既是《金瓶梅》由俗而雅的出版環節之一，又同是讀者意識的展現，乃晚明《金瓶梅》讀者接受與批評不可忽視之材料。 論文第二章首先討論崇禎本《金瓶梅》繡像的形成背景，小說本身的情色描寫與文字特性難以作畫，使崇禎本繡像成為今日唯一流傳之版畫，與其他小說繡像有著文本主題和語言、大量留白、視角、場景等特殊之處，當中可見畫工之詮釋。 　　第三章論證繡像在回目之內的詮釋。視角的選取，代表了畫工面對文本並帶領讀者觀看的閱讀位置，突出隱藏焦點，迫使讀者反思。版畫傳統原本就如傳統繪畫習慣以鳥瞰式「以大觀小」的構圖繡像。無論是版畫傳統下全知視角的客觀，或小說版畫甚少使用的主觀限知視角，其實都可見畫工完全依從回目下仍有著「詮釋」甚至「創作」的企圖心。場景的選擇，崇禎本《金瓶梅》繡像場景大多選擇劇情頂點來表現，或是採取散點透視並置場面突顯衝突性與戲劇性，或是自行選取最能代表人物性格的場面隱藏或彰顯主旨；對於某些情色場景或兇殺、死亡場景等，為了避免混淆重心，或迴避表現頂點的可怖醜陋，畫工就會選擇最富孕育的場景，使讀者用自己的想像去填補其後的發展，並透過最富孕育的場景彰顯此回隱藏的真正重心也暗寓對人物的褒貶。兩種選取的標準各有長處，而畫工能靈活劇情頂點或頂點前之懸念，隱藏世情醜惡並彰顯重心。 　　窺視場景亦不同於其餘艷情小說以女性作為被看的客體，小說本身窺視情色的敘述以及窺視者的性別比例，亦可知《金瓶梅》不同於其餘色情小說是以女性作為被看的客體，事實上比起將女性物化的許多作品，《金瓶梅》本身已暗寓了對弱勢女性生存必需不擇手段的憐憫與同情。小說中偷窺與竊聽層出不窮除了是窺淫的惡趣外，最主要的因素仍是來自人物之間彼此的窺伺偵防。透過視角與佈局指引讀者每一個窺視或潛聽場景，暗示聽覷不僅侵犯並展現了私密空間，此空間更是妻妾為鞏固彼此地位爭寵引妒的戰場，女性或男性都會以自己的身體做為籌碼為自己的生存空間奮鬥，亦或是作為利益交換。每一次的窺視潛聽也都是表現人物心理以及許多險惡人情浮現的契機，是故繡像透過窺視人物指引觀看的劇情場景或情色場面，實際上真正的重心與批判皆在「險之人情」。 　　第四章論繡像在回目限制條件之外的發揮。畫工突破版畫傳統運用大量留白，崇禎本《金瓶梅》繡像與其他小說的不同之處在於有大量的留白，且留白常用於三種場景與作用，另外後二十回的留白則又其他特殊之處。由出現比例與留白則可知，畫工理解小說非淫書，所以不大量強調情色作為宣傳，作畫也不以春宮圖的繁複為傳統，反而有許多留白，此留白不僅是情色的沖淡與遮蓋，更是畫工理解情色場面其實是要帶出小說人物的生存困境與處世態度的昇華與同情。 密謀場景則採取高俯角，將主要場景邊緣化暗寓褒貶；情節相對應之處，採取雷同的構圖，暗示讀者兩相對照。且徽派畫工向來以構圖佈局精麗、變化多端著稱，在崇禎本《金瓶梅》繡像卻有許多重複之處，其實是透過雷同構圖暗示讀者兩相對照，劇情互為因果或有所對應時，畫工往往透過雷同構圖行不言之批判。小說敘述者與評點者未明言提示的興衰以對劇情，畫工亦能透過類似的構圖提示兩相對照，並在構圖中以不同的視角或人物的顯隱去突顯身分以及心理狀態。可見畫工確實對小說有著深刻的理解，能關注到連續敘述者和評點家都未明言的劇情，體會到同樣節慶或場景下照應的是怎樣的世情興衰與境遇浮沉，並能宕出小說與回目之外進行改動，以視角的轉換突出景是人非，以背景的繁疏暗示團圓下的不團圓與其後的悲涼，或是以人物的顯隱突顯姦情之罪總歸咎於何人。繡像之「同」是畫工提醒兩相對照的顯筆，「異」則是表示了畫工理解詮釋所在與隱藏主題的彰顯，可見得除了小說類似說書人的敘述與評點之外，畫工也透過了繡像提供了另一種聲音表達了自己的閱讀態度。 　　甚至新增小說未有之窺視者，指引閱讀隱藏主題，使讀者得以此有利觀看位置入手，避免曲解了小說本文真正的意涵。用意在發揮晚明窺視私密空間甚至窺視情色的風氣，更指引閱讀隱藏主題，繡像新增這些宕出回目與小說文本之外的窺視者，目的是讓讀者透過圖像這樣直觀容易受到制約的強勢媒體，配合小說與評點等各種聲音之外作為一個有利的觀看位置出發觀看小說。 第五章反省崇禎本繡像詮釋文本之缺憾與批評觀點之比較。其缺憾如無法表現豪奢或與小說反諷不符，乃圖像難以突破之限制，以及集體創作之缺陷。然而相較於其他沒有文人介入創作的小說繡像，崇禎本《金瓶梅》繡像已具備更多詮釋性與創新，其觀點與同行之崇批、清代張評、文龍評不盡相同。可見畫工之詮釋乃出自獨創非受書坊指引，所表現的文學意識有著更多的嶄新視角與詮釋態度，改變了我們對小說版畫的刻版印象。

Lightly Weighted Automatic Audio Parameter Extraction for the Quality Assessment of Consensus Auditory-Perceptual Evaluation of Voice

The Consensus Auditory-Perceptual Evaluation of Voice is a widely employed tool in clinical voice quality assessment that is significant for streaming communication among clinical professionals and benchmarking for the determination of further treatment. Currently, because the assessment relies on experienced clinicians, it tends to be inconsistent, and thus, difficult to standardize. To address this problem, we propose to leverage lightly weighted automatic audio parameter extraction, to increase the clinical relevance, reduce the complexity, and enhance the interpretability of voice quality assessment. The proposed method utilizes age, sex, and five audio parameters: jitter, absolute jitter, shimmer, harmonic-to-noise ratio (HNR), and zero crossing. A classical machine learning approach is employed. The result reveals that our approach performs similar to state-of-the-art (SOTA) methods, and outperforms the latent representation obtained by using popular audio pre-trained models. This approach provide insights into the feasibility of different feature extraction approaches for voice evaluation. Audio parameters such as jitter and the HNR are proven to be suitable for characterizing voice quality attributes, such as roughness and strain. Conversely, pre-trained models exhibit limitations in effectively addressing noise-related scorings. This study contributes toward more comprehensive and precise voice quality evaluations, achieved by a comprehensively exploring diverse assessment methodologies.Comment: Published in IEEE 42th International Conference on Consumer Electronics (ICCE 2024

DPRP: a database of phenotype-specific regulatory programs derived from transcription factor binding data

Gene expression profiling has been extensively used in the past decades, resulting in an enormous amount of expression data available in public databases. These data sets are informative in elucidating transcriptional regulation of genes underlying various biological and clinical conditions. However, it is usually difficult to identify transcription factors (TFs) responsible for gene expression changes directly from their own expression, as TF activity is often regulated at the posttranscriptional level. In recent years, technical advances have made it possible to systematically determine the target genes of TFs by ChIP-seq experiments. To identify the regulatory programs underlying gene expression profiles, we constructed a database of phenotype-specific regulatory programs (DPRP, http://syslab.nchu.edu.tw/DPRP/) derived from the integrative analysis of TF binding data and gene expression data. DPRP provides three methods: the Fisher's Exact Test, the Kolmogorov-Smirnov test and the BASE algorithm to facilitate the application of gene expression data for generating new hypotheses on transcriptional regulatory programs in biological and clinical studies