UniHeap: Managing Persistent Objects Across Managed Runtimes for Non-Volatile Memory

Byte-addressable, non-volatile memory (NVM) is emerging as a promising technology. To facilitate its wide adoption, employing NVM in managed runtimes like JVM has proven to be an effective approach (i.e., managed NVM). However, such an approach is runtime specific, which lacks a generic abstraction across different managed languages. Similar to the well-known filesystem primitives that allow diverse programs to access same files via the block I/O interface, managed NVM deserves the same system-wide property for persistent objects across managed runtimes with low overhead. In this paper, we present UniHeap, a new NVM framework for managing persistent objects. It proposes a unified persistent object model that supports various managed languages, and manages NVM within a shared heap that enables cross-language persistent object sharing. UniHeap reduces the object persistence overhead by managing the shared heap in a log-structured manner and coalescing object updates during the garbage collection. We implement UniHeap as a generic framework and extend it to different managed runtimes that include HotSpot JVM, cPython, and JavaScript engine SpiderMonkey. We evaluate UniHeap with a variety of applications, such as key-value store and transactional database. Our evaluation shows that UniHeap significantly outperforms state-of-the-art object sharing approaches, while introducing negligible overhead to the managed runtimes.Comment: A 2 page extended abstract for NVMW 2022

SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect of immunotherapy on retinoblastoma

Purpose: Retinoblastoma (RB) is the most common primary intraocular tumor in children. Chemotherapy is currently the main method of RB treatment. Unfortunately, RB often becomes chemoresistant and turns lethal. Here, we used in vitro cell immunotherapy to explore whether adoptive immunotherapy could be used as a potential treatment for RB. We focused on spleen tyrosine kinase (SYK), which is significantly upregulated in RB cells and serves as a marker for RB cells. Methods: Using lentiviruses, we genetically modified dendritic cells (DCs) to express and present the SYK peptide antigen to cytotoxic T lymphocytes (CTLs) in vitro. We used SYK-negative cell lines (MDA-MB-231, MCF-10A, and hTERT-RPE1) and SYK-positive cell lines (MCF-7 and RB-Y79) to evaluate the specificity and cytotoxicity of DC presented CTLs using FACS, live-cell imaging, and RNA interference. Results: The cytotoxicity of CTLs induced by SYK-overexpressing DCs (SYK-DC–CTLs) was enhanced more than three times in SYK-positive cell lines compared with SYK-negative cell lines. DCs primed with SYK could drive CTL cytotoxicity against SYK-positive cell lines but not against SYK-negative cell lines. Moreover, SYK-silenced RB-Y79 cells successfully evaded the cytotoxic attack from SYK-DC–CTLs. However, SYK-DC–CTLs could target SYK overexpressed hTERT-RPE1 cells, suggesting that SYK is a specific antigen for RB. Furthermore, SYK-DC–CTL exhibited specific cytotoxicity against carboplatin-resistant RB-Y79 cells in vitro. Conclusions: Our data showed that SYK could be a potential immunotherapy target mediated by DCs. We propose SYK as a candidate target for treatment of chemoresistant RB.Fil: Chen, Xuemei. Xi'an Jiaotong University; ChinaFil: Kunda, Patricia Elena. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Lin, Jianwei. Shenzhen University; ChinaFil: Zhou, Meiling. Shenzhen Luohu Peoples Hospital; China. Shenzhen University; ChinaFil: Huang, Jinghan. Shenzhen Luohu Peoples Hospital; ChinaFil: Zhang, Huqin. Xi'an Jiaotong University; ChinaFil: Liu, Tao. Shenzhen University; China. Shenzhen Luohu Peoples Hospital; Chin

Assessing spatiotemporal bikeability using multi-source geospatial big data:A case study of Xiamen, China

This study focuses on the development of a new framework for evaluating bikeability in urban environments with the aim of enhancing sustainable urban transportation planning. To close the research gap that previous studies have disregarded the dynamic environmental factors and trajectory data, we propose a framework that comprises four sub-indices: safety, comfort, accessibility, and vitality. Utilizing open-source data, advanced deep neural networks, and GIS spatial analysis, the framework eliminates subjective evaluations and is more efficient and comprehensive than prior methods. The experimental results on Xiamen, China, demonstrate the effectiveness of the framework in identifying areas for improvement and enhancing cycling mobility. The proposed framework provides a structured approach for evaluating bikeability in different geographical contexts, making reproducing bikeability indices easier and more comprehensive to policymakers, transportation planners, and environmental decision-makers.</p

The QKI-6 and QKI-7 RNA Binding Proteins Block Proliferation and Promote Schwann Cell Myelination

BACKGROUND:The quaking viable (qk(v)) mice have uncompacted myelin in their central and peripheral nervous system (CNS, PNS). The qk gene encodes 3 major alternatively spliced isoforms that contain unique sequence at their C-terminus dictating their cellular localization. QKI-5 is a nuclear isoform, whereas QKI-6 and QKI-7 are cytoplasmic isoforms. The qk(v) mice harbor an enhancer/promoter deletion that prevents the expression of isoforms QKI-6 and QKI-7 in myelinating cells resulting in a dysmyelination phenotype. It was shown that QKI regulates the differentiation of oligodendrocytes, the myelinating cells of the CNS, however, little is known about the role of the QKI proteins, or RNA binding proteins in PNS myelination. METHODOLOGY/PRINCIPAL FINDINGS:To define the role of the QKI proteins in PNS myelination, we ectopically expressed QKI-6 and QKI-7 in primary rat Schwann cell/neuron from dorsal root ganglia cocultures. We show that the QKI isoforms blocked proliferation and promoted Schwann cell differentiation and myelination. In addition, these events were coordinated with elevated proteins levels of p27(KIP1) and myelin basic protein (MBP), markers of Schwann cell differentiation. QKI-6 and QKI-7 expressing co-cultures contained myelinated fibers that had directionality and contained significantly thicker myelin, as assessed by electron microscopy. Moreover, QKI-deficient Schwann cells had reduced levels of MBP, p27(KIP1) and Krox-20 mRNAs, as assessed by quantitative RT-PCR. CONCLUSIONS/SIGNIFICANCE:Our findings suggest that the QKI-6 and QKI-7 RNA binding proteins are positive regulators of PNS myelination and show that the QKI RNA binding proteins play a key role in Schwann cell differentiation and myelination

Case report: A novel case of COVID-19 triggered tumefactive demyelinating lesions in one multiple sclerosis patient

The epidemic of COVID-19 is mainly manifested by respiratory symptoms caused by SARS-CoV-2 infection. Recently, reports of central nervous system diseases caused or aggravated by SARS-CoV-2 infection are also increasing. Thus, the COVID-19 pandemic poses an unprecedented challenge to the diagnosis and management of neurological disorders, especially to those diseases which have overlapping clinical and radiologic features with each other. In this study, a 31-year-old female patient had been diagnosed with relapsing–remitting multiple sclerosis (RRMS) initially and subsequently developed tumefactive demyelinating lesions (TDLs) following an infection with SARS-CoV-2. After immunotherapy (glucocorticoid pulses), a significant improvement was observed in her both clinical and radiological characteristics. The patient was started on disease-modifying therapy (DMT) with teriflunomide after cessation of oral glucocorticoids. Following two months of DMT treatment, the imaging follow-up revealed that the patient’s condition continued to deteriorate. This case was characterized by the transformation of a multiple sclerosis patient (MS) infected with SARS-CoV-2 into TDLs and the ineffectiveness of DMT treatment, which added complexity to its diagnosis and treatment. The case also gave us a hint that SARS-CoV-2 has a potential contributory role in inducing or exacerbating demyelinating diseases of the central nervous system that warrants further investigation

A literature review: mechanisms of antitumor pharmacological action of leonurine alkaloid

Leonurine refers to the desiccated aerial portion of a plant in the Labiatae family. The primary bioactive constituent of Leonurine is an alkaloid, Leonurine alkaloid (Leo), renowned for its substantial therapeutic efficacy in the treatment of gynecological disorders, in addition to its broad-spectrum antineoplastic capabilities. Over recent years, the pharmacodynamic mechanisms of Leo have garnered escalating scholarly interest. Leo exhibits its anticancer potential by means of an array of mechanisms, encompassing the inhibition of neoplastic cell proliferation, induction of both apoptosis and autophagy, and the containment of oncogenic cell invasion and migration. The key signal transduction pathways implicated in these processes include the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), the Phosphoinositide3-Kinase/Serine/Threonine Protein Kinase (PI3K/AKT), the Signal Transducer and Activator of Transcription 3 (STAT3), and the Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase (MAP/ERK). This paper commences with an exploration of the principal oncogenic cellular behaviors influenced by Leo and the associated signal transduction pathways, thereby scrutinizing the mechanisms of Leo in the antineoplastic sequence of events. The intention is to offer theoretical reinforcement for the elucidation of more profound mechanisms underpinning Leo’s anticancer potential and correlating pharmaceutical development

Defining the role of Quaking RNA binding protein and arginine methyltransferase PRMT5 in myelination

Oligodendrocyte differentiation is controlled by a complex network of epigenetic regulators, transcription factors, RNA binding proteins, and cell cycle regulators. The involvement of QKI, an RNA binding protein that regulates mRNA stability, splicing and transport, is only well characterized in rodent myelin development. QKI regulates oligodendrocyte differentiation by controlling in part the expression of cyclin-dependent kinase inhibitor p27 (p27Kip1), a cell cycle inhibitor, and myelin basic protein (MBP), a major myelin component. In this thesis, we first show that human glial progenitor cells readily expressed QKI-6 and QKI-7 but not QKI-5. These cells increased the expression of all three major QKI isoforms as they commit to the OPC lineage and become mature oligodendrocytes. The ectopic QKI-6 and QKI-7 expression promoted human oligodendrocyte differentiation, while QKI-5 played a negative role in this process. Second, we show that protein arginine methyl transferase 5 (PRMT5), an enzyme known to symmetrically dimethylate both QKI and MBP in vitro, was up-regulated during myelin development and indeed methylated MBP in vivo. PRMT5 deficient oligodendrocytes demonstrated impaired differentiation, which was reflected by both the morphology and the transcription factor expression profile. Our findings implicate that QKI-6, QKI-7 and PRMT5 are promoters of oligodendrocyte differentiation, while QKI-5 is an inhibitor of the maturation process.La différenciation d'oligodendrocyte est contrôlée par un réseau complexe de régulateurs épigéniques, de facteurs de transcription, de protéines de liaison à l'ARN ainsi que de régulateurs du cycle cellulaire. L'implication de QKI, une protéine de liaison à l'ARN qui régule la stabilité, l'épissage et le transport de l'ARNm, n'est que bien caractérisée dans le développement de la myéline chez les rongeurs. En régulant l'expression de p27Kip1, un inhibiteur du cycle cellulaire, ainsi que MBP, un composant majeur de la myéline, QKI-6 et QKI-7 stimulent tandis que QKI-5 réprime la différenciation d'oligodendrocytes. Nous avons démontré que les effets d'une expression exogène de QKI chez des oligodendrocytes humains sont consistants avec ceux observés chez les cellules des rongeurs. On a d'ailleurs établi que PRMT5, une enzyme capable de méthyler QKI ainsi que MBP in vitro, est régulée positivement pendant le développement de la myéline du SNC. De plus, nous avons confirmé que MBP est méthylé par PRMT5 in vivo. L'ablation de PRMT5 dans les oligodendrocytes résulte en une différenciation anormale, ainsi caractérisée morphologiquement et en étudiant le profil des facteurs de transcription. Prise ensemble, ces résultats suggèrent que PRMT5 est un promoteur de la différenciation d'oligodendrocytes

Research on Adversarial Domain Adaptation Method and Its Application in Power Load Forecasting

Domain adaptation has been used to transfer the knowledge from the source domain to the target domain where training data is insufficient in the target domain; thus, it can overcome the data shortage problem of power load forecasting effectively. Inspired by Generative Adversarial Networks (GANs), adversarial domain adaptation transfers knowledge in adversarial learning. Existing adversarial domain adaptation faces the problems of adversarial disequilibrium and a lack of transferability quantification, which will eventually decrease the prediction accuracy. To address this issue, a novel adversarial domain adaptation method is proposed. Firstly, by analyzing the causes of the adversarial disequilibrium, an initial state fusion strategy is proposed to improve the reliability of the domain discriminator, thus maintaining the adversarial equilibrium. Secondly, domain similarity is calculated to quantify the transferability of source domain samples based on information entropy; through weighting in the process of domain alignment, the knowledge is transferred selectively and the negative transfer is suppressed. Finally, the Building Data Genome Project 2 (BDGP2) dataset is used to validate the proposed method. The experimental results demonstrate that the proposed method can alleviate the problem of adversarial disequilibrium and reasonably quantify the transferability to improve the accuracy of power load forecasting