Microstructure evolution during high-pressure spark plasma sintering (HPSPS) of transparent alumina

Applying high-pressure during spark plasma sintering (so-called HPSPS) enables rapid densification of a ceramic powder at relatively lower temperatures, limiting grain growth and allowing fabrication of fine-grained highly transparent ceramics. The present work focuses on the fabrication of fine submicron transparent alumina from untreated commercial powder by HPSPS and the microstructure evolution during consolidation under high applied pressure. The sintering was conducted at relatively low temperatures (1000-1100°C) under high pressure varied from 250 to 800 MPa. We review unique sintering phenomena such as stress-enhanced grain growth and de-sintering, which are related to creep taking place during the final stage of pressure-assisted densification. In addition, optical and mechanical properties of obtained samples are discussed. Please click Additional Files below to see the full abstract

Photoluminescence in SPS-processed transparent Ce:YAG ceramics

Ceramic phosphors display great promise for the realization of high-power lighting devices. Cerium-doped yttrium aluminum garnet (Ce:YAG) is commonly used as a phosphor in white light emitting diodes. Therefore, it was chosen as a case study to investigate photoluminescence of transparent ceramic phosphors fabricated by spark plasma sintering (SPS). In the present work, 0.5 at.% Ce:YAG nano-powder was synthesized by a co-precipitation method and subsequently consolidated by SPS into highly transparent ceramic samples. The effect of varying sintering parameters (temperature and pressure) and post-sintering treatments (hot isostatic pressing and air atmosphere thermal treatment) on optical properties was investigated. Correlations between in-line transmittance, photoluminescence (PL) and residual porosity characteristics (pore size and volume fraction) were established. It was also found that PL emission intensity and external quantum efficiency were significantly affected by intentionally created surface roughness. Please click Additional Files below to see the full abstract

The prospect of tumor microenvironment-modulating therapeutical strategies

Multiple mechanisms promote tumor prosperity, which does not only depend on cell-autonomous, inherent abnormal characteristics of the malignant cells that facilitate rapid cell division and tumor expansion. The neoplastic tissue is embedded in a supportive and dynamic tumor microenvironment (TME) that nurtures and protects the malignant cells, maintaining and perpetuating malignant cell expansion. The TME consists of different elements, such as atypical vasculature, various innate and adaptive immune cells with immunosuppressive or pro-inflammatory properties, altered extracellular matrix (ECM), activated stromal cells, and a wide range of secreted/stroma-tethered bioactive molecules that contribute to malignancy, directly or indirectly. In this review, we describe the various TME components and provide examples of anti-cancer therapies and novel drugs under development that aim to target these components rather than the intrinsic processes within the malignant cells. Combinatory TME-modulating therapeutic strategies may be required to overcome the resistance to current treatment options and prevent tumor recurrence

Immunoglobulin variable-region gene mutational lineage tree analysis: application to autoimmune diseases

Lineage trees have frequently been drawn to illustrate diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. In order to extract more information from IGV sequences, we developed a novel mathematical method for analyzing the graphical properties of IgV gene lineage trees, allowing quantification of the differences between the dynamics of SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we investigated trees generated from published IGV sequence data from B cell clones participating in autoimmune responses in patients with Myasthenia Gravis (MG), Rheumatoid Arthritis (RA), and Sjögren's Syndrome (SS). At present, as no standards exist for cell sampling and sequence extraction methods, data obtained by different research groups from two studies of the same disease often vary considerably. Nevertheless, based on comparisons of data groups within individual studies, we show here that lineage trees from different individual patients are often similar and can be grouped together, as can trees from two different tissues in the same patient, and even from IgG- and IgA-expressing B cell clones. Additionally, lineage trees from most studies reflect the chronic character of autoimmune diseases

Tyrosine Kinase Inhibitors Induced Immune Thrombocytopenia in Chronic Myeloid Leukemia?

The outcome and quality of life of chronic myeloid leukemia (CML) patients has remarkably changed with the treatment of tyrosine kinase inhibitors (TKIs). Currently, hematopoietic stem cell transplantation (HSCT) is considered mainly as a third line salvage therapy in cases of TKIs resistance or intolerance. Here we describe a patient with chronic phase CML who developed both resistance and late occurrence of s severe thrombocytopenia on first and second generation TKIs and eventually underwent HSCT. Although the mechanism of the myelosuppression is not fully understood, we showed for the first time the development of dose dependent platelet antibodies in the presence of TKIs, suggesting the possibility of TKIs induced thrombocytopenia. Our case emphasizes that late development of severe myelosuppression during imatinib treatment is probably an important indication for consideration of early HSCT

Postoperative CRP Levels Can Rule out Anastomotic Leaks in Crohn’s Disease Patients

Background: In colorectal cancer, C-reactive protein (CRP) levels on postoperative days 3–4 have a strong negative predictive value for an anastomotic leak, with threshold values of ~15 on post-operative day (POD) 3 and ~13 on POD 4. In Crohn’s disease, CRP levels are perceived as unreliable in the postoperative period because of the underlying inflammatory process. The aim of this study was to determine whether postoperative CRP levels can be used to rule out anastomotic leaks in patients with Crohn’s disease and to set CRP threshold values for this population. Methods: This was a retrospective study of a population of Crohn’s disease patients who underwent surgery with bowel anastomoses at a single high-volume center between 1/2012 and 12/2017. The operations were performed by a single colorectal consultant who is an inflammatory bowel disease specialist. Results: Ninety-two operations were performed. A CRP level of 19.56 mg/dL on postoperative day 3 had an area under the curve of 0.865 (sensitivity 88%, specificity 73%) and a negative predictive value (NPV) of 98% for an anastomotic leak. Patients with an anastomotic leak showed a trend towards decreased postoperative albumin levels (p = 0.06). Conclusions: Mean CRP levels and CRP threshold values were indeed higher in the study population compared with those in colorectal cancer patients. Threshold values were set at 20.3 mg/dL on POD 3, 19.5 mg/dL on POD 4 and 16.7 mg/dL on POD 5. These values had high NPVs and can be used to rule out anastomotic leaks in patients with Crohn’s disease after surgery with bowel anastomosis

Table_1_The prospect of tumor microenvironment-modulating therapeutical strategies.docx

Multiple mechanisms promote tumor prosperity, which does not only depend on cell-autonomous, inherent abnormal characteristics of the malignant cells that facilitate rapid cell division and tumor expansion. The neoplastic tissue is embedded in a supportive and dynamic tumor microenvironment (TME) that nurtures and protects the malignant cells, maintaining and perpetuating malignant cell expansion. The TME consists of different elements, such as atypical vasculature, various innate and adaptive immune cells with immunosuppressive or pro-inflammatory properties, altered extracellular matrix (ECM), activated stromal cells, and a wide range of secreted/stroma-tethered bioactive molecules that contribute to malignancy, directly or indirectly. In this review, we describe the various TME components and provide examples of anti-cancer therapies and novel drugs under development that aim to target these components rather than the intrinsic processes within the malignant cells. Combinatory TME-modulating therapeutic strategies may be required to overcome the resistance to current treatment options and prevent tumor recurrence.</p

Pressure-assisted sintering and characterization of Nd:YAG ceramic lasers

Abstract Spark plasma sintering (SPS) is an advanced one-stage, rapid, near-net shape densification technique combining uniaxial pressure with resistive heating. Various transparent ceramics have been successfully fabricated by SPS, despite the existence of inherent carbon contamination and residual pores. Due to the disk-shape of SPS-processed samples, the technique may be suited for producing thin-disk ceramic laser materials. Nevertheless, an in-depth study of these materials has never been reported. With that goal in mind, the major focus of this study was to characterize the laser performance of Nd:YAG ceramics fabricated by one-stage SPS under conventional (60 MPa) and high (300 MPa) applied pressures. In addition to measuring the lasing slope efficiency and threshold, the passive losses associated with each sample were also evaluated. Surprisingly, it was found that in-line transmittance spectra do not provide accurate predictions of laser performance due to the nature of residual porosity. Moreover, homogeneity and beam quality were assessed, and comparisons were drawn between conventional and high-pressure SPS ceramics. This study lays the groundwork for the future of laser materials fabricated by SPS or similar pressure-assisted techniques