Shear Bond Strength Evaluation of Composite versus Glass Ionomer Cement Over One Year

Role and Significance of Restorative Dental Materials1 Composite resin is a widely used restorative material, because of its esthetic properties, biocompatibility, and more importantly its low environmental impact. The properties of a restorative material require significant durability, strength and withstand degradation of the restoration when subjected to different factors in the oral cavity. The oral environment is a complex environment where a restorative material must be able to sustain against bacteria, changing pH, temperature, masticatory forces and saliva etc. The oral cavity is considered to be the harshest environment for a dental material in the body. Glass ionomer cements (GIC) are the only direct restorative material to bond chemically to dental hard tissues due to the formation of ionic bonds between carboxylate groups and calcium. The propertities of GIC include adhesion to moist tooth structures, anticariogenic properties due to release of fluoride, thermal compatibility with tooth enamel, biocompatibility and low toxicity. The use of GICs in a mechanically loaded situation, however, has been hampered by their low mechanical performance. Poor mechanical properties, such as low fracture strength, toughness and wear, limit their extensive use in dentistry as a filling material in stress-bearing applications. In the posterior dental region, glass ionomer cements are mostly used as a temporary filling material. The requirement to strengthen those cements has led to an ever-increasing research effort into reinforcement or strengthening concepts. Shear Bond Testing is an established method to evaluate the bond strength between dental hard tissue and restorative materials.2,

With eyes unclouded

Tiffany is interested in creating purposeful connections and direct relationships through this vehicle of functional work. The scale of the work is made for the tabletop, asking to be handled and enjoyed. Her work takes a lot of time. Everything she does to the piece has a purpose. There are many stages in the process, and each informs what the next step will be, leading to the work existing as an accumulation of experiences. The use of colors and patterns are a form of inviting joy into the work. Blue greens, dark teals, serenity blues, pastel pinks, rosy quartz, palest yellows, lavender blushes, lilacs, and orchids. Tiffany finds meaning by affecting others through her work, creating the connection when the work is in use. She finds ways to make up for the loss and insurmountable sadness she has in her life by connecting with humanity within her work using the visual, tactile, and function. As trauma is a loss of the self, you are forever trying to get back what you had lost only to find that you can\u27t. By creating connections beyond the transitional with her work, the charisma and the perfection of the pottery is very much about bridging the divide of that loss. By seeing the value of growth through pain, she wants people to be drawn into this beauty to find a shared human connection. The work has a constant humanity that never falls away, but instead transforms with people as time moves forward. Tiffany wants to be able to touch people\u27s lives by bringing forth beauty in the world, even in the smallest ways

Biochemical and Genetic Conservation of Fission Yeast DSK1 and Human SRPK1

Arginine/serine-rich (RS) domain-containing proteins and their phosphorylation by specific protein kinases constitute control circuits to regulate pre-mRNA splicing and coordinate splicing with transcription in mammalian cells. We present here the finding that similar SR networks exist in Schizosaccharomyces pombe. We previously showed that Dsk1 protein, originally described as a mitotic regulator, displays high activity in phosphorylating S. pombe Prp2 protein (spU2AF59), a homologue of human U2AF65. We now demonstrate that Dsk1 also phosphorylates two recently identified fission yeast proteins with RS repeats, Srp1 and Srp2, in vitro. The phosphorylated proteins bear the same phosphoepitope found in mammalian SR proteins. Consistent with its substrate specificity, Dsk1 forms kinase-competent complexes with those proteins. Furthermore, dsk1+ gene determines the phenotype of prp2+ overexpression, providing in vivo evidence that Prp2 is a target for Dsk1. The dsk1-null mutant strain became severely sick with the additional deletion of a related kinase gene. Significantly, human SR protein-specific kinase 1 (SRPK1) complements the growth defect of the double-deletion mutant. In conjunction with the resemblance of dsk1+ and SRPK1 in sequence homology, biochemical properties, and overexpression phenotypes, the complementation result indicates that SRPK1 is a functional homologue of Dsk1. Collectively, our studies illustrate the conserved SR networks in S. pombe consisting of RS domain-containing proteins and SR protein-specific kinases and thus establish the importance of the networks in eucaryotic organisms

Designing a Data Science simulation with MERITS: A Primer

Simulations play a crucial role in the modern scientific process. Yet despite (or due to) their ubiquity, the Data Science community shares neither a comprehensive definition for a "high-quality" study nor a consolidated guide to designing one. Inspired by the Predictability-Computability-Stability (PCS) framework for 'veridical' Data Science, we propose six MERITS that a Data Science simulation should satisfy. Modularity and Efficiency support the Computability of a study, encouraging clean and flexible implementation. Realism and Stability address the conceptualization of the research problem: How well does a study Predict reality, such that its conclusions generalize to new data/contexts? Finally, Intuitiveness and Transparency encourage good communication and trustworthiness of study design and results. Drawing an analogy between simulation and cooking, we moreover offer (a) a conceptual framework for thinking about the anatomy of a simulation 'recipe'; (b) a baker's dozen in guidelines to aid the Data Science practitioner in designing one; and (c) a case study deconstructing a simulation through the lens of our framework to demonstrate its practical utility. By contributing this "PCS primer" for high-quality Data Science simulation, we seek to distill and enrich the best practices of simulation across disciplines into a cohesive recipe for trustworthy, veridical Data Science.Comment: 26 pages (main text); 1 figure; 2 tables; *Authors contributed equally to this manuscript; **Authors contributed equally to this manuscrip

Priming Leukemia with 5-Azacytidine Enhances CAR T Cell Therapy

Purpose: Despite the success of chimeric antigen receptor (CAR) T cells in clinical studies, a significant proportion of responding patients eventually relapsed, with the latter correlating with low CAR T cell expansion and persistence. Methods and Results: Using patient-derived xenograft (PDX) mouse models of CD19+ B cell acute lymphoblastic leukemia (B-ALL), we show that priming leukemia-bearing mice with 5-azacytidine (AZA) enhances CAR T cell therapy. AZA given 1 day prior to CAR T cell infusion delayed leukemia growth and promoted CAR T cell expansion and effector function. Priming leukemia cells with AZA increased CAR T cell/target cell conjugation and target cell killing, promoted CAR T cell divisions and expanded IFNγ+ effector T cells in co-cultures with CD19+ leukemia Nalm-6 and Raji cells. Transcriptome analysis revealed activation of diverse immune pathways in leukemia cells isolated from mice treated with AZA. We propose that epigenetic priming with AZA induces transcriptional changes that sensitize tumor cells to subsequent CAR T cell treatment. Among the candidate genes up-regulated by AZA is TNFSF4 which encodes OX40L, one of the strongest T cell co-stimulatory ligands. OX40L binds OX40, the TNF receptor superfamily member highly specific for activated T cells. TNFSF4 is heterogeneously expressed in a panel of pediatric PDXs, and high TNFSF4 expression correlated with increased CAR T cell numbers identified in co-cultures with individual PDXs. High OX40L expression in Nalm-6 cells increased their susceptibility to CAR T cell killing while OX40L blockade reduced leukemia cell killing. Conclusion: We propose that treatment with AZA activates OX40L/OX40 co-stimulatory signaling in CAR T cells. Our data suggest that the clinical use of AZA before CAR T cells could be considered

Peripheral T-Cell Lymphoma: Review and Updates of Current Management Strategies

The classification of T-cell and natural-killer- (NK-) cell lymphomas has been updated in the 4th edition of the World Health Organization (WHO) classification of tumors of the haematopoietic and lymphoid tissue published in 2008. Based on recent epidemiological studies, NK-cell lymphomas occur almost exclusively in Asia and South America, although T-cell lymphomas appear to occur in the East as commonly as in the West. Due to the low prevalence of this disease, diagnosis and optimal treatment of patients have not been studied prospectively in large randomized trials. Nevertheless, there has been development in the understanding of T-cell lymphomas and how they should be managed; FDG-PET emerges as an increasingly important tool in diagnosis, gene-expression signatures may aid with prognostication in the future, and novel therapies are currently being studied to improve outcomes in T-cell lymphomas. More work, however, needs to be done, and international collaboration will be pertinent to deriving meaningful results from future clinical studies

Functional equivalence of stem cell and stem cell-derived extracellular vesicle transplantation to repair the irradiated brain.

Cranial radiotherapy, although beneficial for the treatment of brain tumors, inevitably leads to normal tissue damage that can induce unintended neurocognitive complications that are progressive and debilitating. Ionizing radiation exposure has also been shown to compromise the structural integrity of mature neurons throughout the brain, an effect believed to be at least in part responsible for the deterioration of cognitive health. Past work has shown that cranially transplanted human neural stem cells (hNSCs) or their extracellular vesicles (EVs) afforded long-term beneficial effects on many of these cognitive decrements. To provide additional insight into the potential neuroprotective mechanisms of cell-based regenerative strategies, we have analyzed hippocampal neurons for changes in structural integrity and synaptic remodeling after unilateral and bilateral transplantation of hNSCs or EVs derived from those same cells. Interestingly, hNSCs and EVs similarly afforded protection to host neurons, ameliorating the impact of irradiation on dendritic complexity and spine density for neurons present in both the ipsilateral and contralateral hippocampi 1 month following irradiation and transplantation. These morphometric improvements were accompanied by increased levels of glial cell-derived growth factor and significant attenuation of radiation-induced increases in postsynaptic density protein 95 and activated microglia were found ipsi- and contra-lateral to the transplantation sites of the irradiated hippocampus treated with hNSCs or hNSC-derived EVs. These findings document potent far-reaching neuroprotective effects mediated by grafted stem cells or EVs adjacent and distal to the site of transplantation and support their potential as therapeutic agents to counteract the adverse effects of cranial irradiation

Integrated Proteotranscriptomics of Breast Cancer Reveals Globally Increased Protein-mRNA Concordance Associated with Subtypes and Survival

BACKGROUND: Transcriptome analysis of breast cancer discovered distinct disease subtypes of clinical significance. However, it remains a challenge to define disease biology solely based on gene expression because tumor biology is often the result of protein function. Here, we measured global proteome and transcriptome expression in human breast tumors and adjacent non-cancerous tissue and performed an integrated proteotranscriptomic analysis. METHODS: We applied a quantitative liquid chromatography/mass spectrometry-based proteome analysis using an untargeted approach and analyzed protein extracts from 65 breast tumors and 53 adjacent non-cancerous tissues. Additional gene expression data from Affymetrix Gene Chip Human Gene ST Arrays were available for 59 tumors and 38 non-cancerous tissues in our study. We then applied an integrated analysis of the proteomic and transcriptomic data to examine relationships between them, disease characteristics, and patient survival. Findings were validated in a second dataset using proteome and transcriptome data from The Cancer Genome Atlas and the Clinical Proteomic Tumor Analysis Consortium. RESULTS: We found that the proteome describes differences between cancerous and non-cancerous tissues that are not revealed by the transcriptome. The proteome, but not the transcriptome, revealed an activation of infection-related signal pathways in basal-like and triple-negative tumors. We also observed that proteins rather than mRNAs are increased in tumors and show that this observation could be related to shortening of the 3\u27 untranslated region of mRNAs in tumors. The integrated analysis of the two technologies further revealed a global increase in protein-mRNA concordance in tumors. Highly correlated protein-gene pairs were enriched in protein processing and disease metabolic pathways. The increased concordance between transcript and protein levels was additionally associated with aggressive disease, including basal-like/triple-negative tumors, and decreased patient survival. We also uncovered a strong positive association between protein-mRNA concordance and proliferation of tumors. Finally, we observed that protein expression profiles co-segregate with a Myc activation signature and separate breast tumors into two subgroups with different survival outcomes. CONCLUSIONS: Our study provides new insights into the relationship between protein and mRNA expression in breast cancer and shows that an integrated analysis of the proteome and transcriptome has the potential of uncovering novel disease characteristics