TENSILE: A Tensor granularity dynamic GPU memory scheduling method towards multiple dynamic workloads system

Recently, deep learning has been an area of intense research. However, as a kind of computing-intensive task, deep learning highly relies on the scale of GPU memory, which is usually prohibitive and scarce. Although there are some extensive works have been proposed for dynamic GPU memory management, they are hard to be applied to systems with multiple dynamic workloads, such as in-database machine learning systems. In this paper, we demonstrated TENSILE, a method of managing GPU memory in tensor granularity to reduce the GPU memory peak, considering the multiple dynamic workloads. TENSILE tackled the cold-starting and across-iteration scheduling problem existing in previous works. We implement TENSILE on a deep learning framework built by ourselves and evaluated its performance. The experiment results show that TENSILE can save more GPU memory with less extra time overhead than prior works in both single and multiple dynamic workloads scenarios

WolfPath : accelerating iterative traversing-based graph processing algorithms on GPU

There is the significant interest nowadays in developing the frameworks of parallelizing the processing for the large graphs such as social networks, Web graphs, etc. Most parallel graph processing frameworks employ iterative processing model. However, by benchmarking the state-of-art GPU-based graph processing frameworks, we observed that the performance of iterative traversing-based graph algorithms (such as Bread First Search, Single Source Shortest Path and so on) on GPU is limited by the frequent data exchange between host and GPU. In order to tackle the problem, we develop a GPU-based graph framework called WolfPath to accelerate the processing of iterative traversing-based graph processing algorithms. In WolfPath, the iterative process is guided by the graph diameter to eliminate the frequent data exchange between host and GPU. To accomplish this goal, WolfPath proposes a data structure called Layered Edge list to represent the graph, from which the graph diameter is known before the start of graph processing. In order to enhance the applicability of our WolfPath framework, a graph preprocessing algorithm is also developed in this work to convert any graph into the format of the Layered Edge list. We conducted extensive experiments to verify the effectiveness of WolfPath. The experimental results show that WolfPath achieves significant speedup over the state-of-art GPU-based in-memory and out-of-memory graph processing frameworks

Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies

Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies

YWHAZ gene contributes to the radioresistance of oral squamous cell carcinoma cells

Objective: To investigate the contribution of YWHAZ gene on the radioresistance and metastasis ability of oral squamous cell carcinoma (OSCC) cells. Methods: The relationship between the expression level of YWHAZ gene and the survival of head and neck squamous cell carcinoma (HNSC) patients was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) database. A radioresistance cell line (CAL-27R) was constructed by irradiating CAL-27 ​cells with fractional doses. Cell survival was measured by colony formation assay. Cell migration and invasion were detected by transwell assay. The formation of γH2AX foci was detected by immunofluorescence assay. The protein expressions were detected by Western blot assay. In some experiments, CAL-27R cells were effectively transferred with siRNA YWHAZ (siYWHAZ). Results: GEPIA database showed that the expression level of YWHAZ in HNSC tumors was higher than that in adjacent normal tissues, and the HNSC patients with higher level of YWHAZ had a shorter survival. In vitro experiments demonstrated that the expression of YWHAZ protein in CAL-27 ​cells was lower than HSC-3 ​cells (t ​= ​18.89, P ​< ​0.01) and radioresistant CAL-27R cells (t ​= ​25.70, P ​< ​0.01). Knockdown of YWHAZ gene significantly increased radiation-induced cell killing effect, apoptosis induction, and γH2AX foci formation in CAL-27R and HSC-3 cells. Moreover, siRNA YWHAZ transfection also reduced the invasion and migration abilities of the irradiated CAL-27R [(t ​= ​21.09, P<0.01 (migration); t ​= ​6.16, P<0.05 (invasion)] and HSC-3 ​cells [(t = 34.53, P < 0.001 (migration); t ​= ​4.92, P ​< ​0.05 (invasion)] and attenuated radiation-induced expressions of metastasis-related proteins. Conclusion: YWHAZ contributes to the radioresistance of oral squamous cells and thus it may applicable to be a potential target for OSCC radiotherapy

GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells

Radiotherapy is one of the conventional methods for the clinical treatment of breast cancer. However, radioresistance has an adverse effect on the prognosis of breast cancer patients after radiotherapy. In this study, using bioinformatic analysis of GSE59732 and GSE59733 datasets in the Gene Expression Omnibus (GEO) database together with the prognosis database of breast cancer patients after radiotherapy, the GDF15 gene was screened out to be related to the poor prognosis of breast cancer after radiotherapy. Compared with radiosensitive parental breast cancer cells, breast cancer cells with acquired radioresistance exhibited a high level of GDF15 expression and enhanced epithelial-to-mesenchymal transition (EMT) properties of migration and invasion, as well as obvious stem-like traits, including the increases of mammosphere formation ability, the proportion of stem cells (CD44+ CD24&minus; cells), and the expressions of stem cell-related markers (SOX2, NANOG). Moreover, knockdown of GDF15 sensitized the radioresistance cells to irradiation and significantly inhibited their EMT and stem-like traits, indicating that GDF15 promoted the radioresistance of breast cancer by enhancing the properties of EMT and stemness. Conclusively, GDF15 may be applicable as a novel prognosis-related biomarker and a potential therapeutic target for breast cancer radiotherapy

MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Radiotherapy has long been an important treatment method of GBM. However, the intrinsic radioresistance of GBM cells is a key reason of poor therapeutic efficiency. Recently, many studies have shown that using the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) in radiotherapy may improve the prognosis of GBM patients, but the underlying molecular mechanisms remain unclear. In this study, Gene Expression Omnibus (GEO) datasets GSE153982 and GSE131956 were analyzed to evaluate radiation-induced changes of gene expression in GBM without or with SAHA treatment, respectively. Additionally, the survival-associated genes of GBM patients were screened using the Chinese Glioma Genome Atlas (CGGA) database. Taking the intersection of these three datasets, 11 survival-associated genes were discovered to be activated by irradiation and regulated by SAHA. The expressions of these genes were further verified in human GBM cell lines U251, T98G, and U251 homologous radioresistant cells (U251R) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). It was found that MMP14 mRNA was considerably highly expressed in the radioresistant cell lines and was reduced by SAHA treatment. Transfection of MMP14 siRNA (siMMP14) suppressed cell survivals of these GBM cells after irradiation. Taken together, our results reveal for the first time that the MMP14 gene contributed to SAHA-induced radiosensitization of GBM

CD81 Enhances Radioresistance of Glioblastoma by Promoting Nuclear Translocation of Rad51

Glioblastoma (GBM) is the most common type of primary tumor in central nervous system in adult with a 5-year survival rate of ≤5%. Despite of recent advances in tumor radiotherapy, the prognosis of GBM remains to be dismal due to radioresistance. In this study, we identified CD81 as a potential biomarker of GBM radioresistance with the analysis of upregulated genes in human glioma radioresistant cell lines U251R and T98G in comparison with U251 cells. In vitro and in vivo experiments demonstrated that suppressing CD81 by siRNA/shRNA enhanced radiation-induced cell killing and DNA damage of γ-H2AX formation, and delayed tumor xenograft growth of GBM. Mechanistically, we found that knockdown of CD81 significantly decreased radiation-induced expression of nuclear Rad51, a key protein involved in homologous recombination repair (HRR) of DNA, suggesting that CD81 is essential for DNA damage response. Meanwhile, when the cells were treated with B02, a Rad51 inhibitor, silencing CD81 would not sensitize GBM cells to radiation, which further illustrates that Rad51 acts as an effector protein of CD81 in tumor radioresistance. Dual immunofluorescence staining of CD81 and Rad51 illustrated that nuclear membrane CD81 contributed to the nuclear transport of Rad51 after irradiation. In conclusion, we demonstrated for the first time that CD81 not only played a vital role in DNA repair through regulating Rad51 nuclear transport, but also might serve as a potential target of GBM radiotherapy

Intrinsically bioactive and biomimetic nanoparticle-derived therapies alleviate asthma by regulating multiple pathological cells

Asthma is a serious global public health concern. Airway neutrophilic inflammation is closely related to severe asthma, for which effective and safe therapies remain to be developed. Here we report nanotherapies capable of simultaneously regulating multiple target cells relevant to the pathogenesis of neutrophilic asthma. A nanotherapy LaCD NP based on a cyclic oligosaccharide-derived bioactive material was engineered. LaCD NP effectively accumulated in the injured lungs of asthmatic mice and mainly distributed in neutrophils, macrophages, and airway epithelial cells after intravenous or inhalation delivery, thereby ameliorating asthmatic symptoms and attenuating pulmonary neutrophilic inflammation as well as reducing airway hyperresponsiveness, remodeling, and mucus production. Surface engineering via neutrophil cell membrane further enhanced targeting and therapeutic effects of LaCD NP. Mechanistically, LaCD NP can inhibit the recruitment and activation of neutrophils, especially reducing the neutrophil extracellular traps formation and NLRP3 inflammasome activation in neutrophils. Also, LaCD NP can suppress macrophage-mediated pro-inflammatory responses and prevent airway epithelial cell death and smooth muscle cell proliferation, by mitigating neutrophilic inflammation and its direct effects on relevant cells. Importantly, LaCD NP showed good safety performance. Consequently, LaCD-derived multi-bioactive nanotherapies are promising for effective treatment of neutrophilic asthma and other neutrophil-associated diseases