Linking 3DP manufacturing with SIFT-MS volatiles organic compound analysis

3D printing (3DP) oral solid dose forms by Fused Filament Fabrication has gained increased interest in recent years. To facilitate efficient formulation and process development, some studies developed and implemented rheological and mechanical screening tests [1-3]. However, changes in the formulated polymeric system due to processing at elevated temperatures and shear have not been addressed. In this study, SIFT-MS Volatiles Organic Compound Analysis was employed to monitor a 3DP manufacturing process

Temporal Modulation of Traveling Waves in the Flow Between Rotating Cylinders With Broken Azimuthal Symmetry

The effect of temporal modulation on traveling waves in the flows in two distinct systems of rotating cylinders, both with broken azimuthal symmetry, has been investigated. It is shown that by modulating the control parameter at twice the critical frequency one can excite phase-locked standing waves and standing-wave-like states which are not allowed when the system is rotationally symmetric. We also show how previous theoretical results can be extended to handle patterns such as these, that are periodic in two spatial direction.Comment: 17 pages in LaTeX, 22 figures available as postscript files from http://www.esam.nwu.edu/riecke/lit/lit.htm

Fc receptor-like 5 and anti-CD20 treatment response in granulomatosis with polyangiitis and microscopic polyangiitis

BACKGROUND. Baseline expression of FCRL5, a marker of naive and memory B cells, was shown to predict response to rituximab (RTX) in rheumatoid arthritis. This study investigated baseline expression of FCRL5 as a potential biomarker of clinical response to RTX in granulomatosis with polyangiitis (CPA) and microscopic polyangiitis (MPA). METHODS. A previously validated quantitative PCR-based (qPCR-based) platform was used to assess FCRL5 expression in patients with GPA/MPA (RAVE trial, NCT00104299). RESULTS. Baseline FCRL5 expression was significantly higher in patients achieving complete remission (CR) at 6,12, and 18 months, independent of other clinical and serological variables, among those randomized to RTX but not cyclophosphamide-azathioprine (CYC/AZA). Patients with baseline FCRL5 expression >= 0.01 expression units (termed FCRL5(hi)) exhibited significantly higher CR rates at 6,12, and 18 months as compared with FCRL5(lo) subjects (84% versus 57% [P = 0.016], 68% versus 40% [P = 0.02], and 68% versus 29% [P = 0.0009], respectively). CONCLUSION. Our data taken together suggest that FCRL5 is a biomarker of B cell lineage associated with increased achievement and maintenance of complete remission among patients treated with RTX and warrant further investigation in a prospective manner

Myeloid/Microglial driven autologous hematopoietic stem cell gene therapy corrects a neuronopathic lysosomal disease

Mucopolysaccharidosis type IIIA (MPSIIIA) is a lysosomal storage disorder caused by mutations in N-sulfoglucosamine sulfohydrolase (SGSH), resulting in heparan sulfate (HS) accumulation and progressive neurodegeneration. There are no treatments. We previously demonstrated improved neuropathology in MPSIIIA mice using lentiviral vectors (LVs) overexpressing SGSH in wild-type (WT) hematopoietic stem cell (HSC) transplants (HSCTs), achieved via donor monocyte/microglial engraftment in the brain. However, neurological disease was not corrected using LVs in autologous MPSIIIA HSCTs. To improve brain expression via monocyte/microglial specificity, LVs expressing enhanced green fluorescent protein (eGFP) under ubiquitous phosphoglycerate kinase (PGK) or myeloid-specific promoters were compared in transplanted HSCs. LV-CD11b-GFP gave significantly higher monocyte/B-cell eGFP expression than LV-PGK-GFP or LV-CD18-GFP after 6 months. Subsequently, autologous MPSIIIA HSCs were transduced with either LV-PGK-coSGSH or LV-CD11b-coSGSH vectors expressing codon-optimized SGSH and transplanted into MPSIIIA mice. Eight months after HSCT, LV-PGK-coSGSH vectors produced bone marrow SGSH (576% normal activity) similar to LV-CD11b-coSGSH (473%), but LV-CD11b-coSGSH had significantly higher brain expression (11 versus 7%), demonstrating improved brain specificity. LV-CD11b-coSGSH normalized MPSIIIA behavior, brain HS, GM2 ganglioside, and neuroinflammation to WT levels, whereas LV-PGK-coSGSH partly corrected neuropathology but not behavior. We demonstrate compelling evidence of neurological disease correction using autologous myeloid driven lentiviral-HSC gene therapy in MPSIIIA mice. © The American Society of Gene & Cell Therapy

A critical review of the formation of mono- and dicarboxylated metabolic intermediates of alkylphenol polyethoxylates during wastewater treatment and their environmental significance

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.Alkylphenoxyacetic acids, the metabolic biodegradation products of alkylphenol ethoxylates, are commonly found in wastewaters and sewage effluents. These persistent hydrophilic derivatives possess intrinsic estrogenic activity, which can mimic natural hormones. Their concentrations increase through the sewage treatment works as a result of biodegradation and biotransformation, and when discharged can disrupt endocrine function in fish. These acidic metabolites represent the dominant alkylphenolic compounds found in wastewater effluent and their presence is cause for concern as, potentially, through further biotransformation and biodegradation, they can act as sources of nonylphenol, which is toxic and estrogenic. The authors aim to assess the mechanisms of formation as well as elimination of alkylphenoxyacetic acids within conventional sewage treatment works with the emphasis on the activated sludge process. In addition, they evaluate the various factors influencing their degradation and formation in laboratory scale and full-scale systems. The environmental implications of these compounds are considered, as is the need for tertiary treatment processes for their removal

PINCH is an independent prognostic factor in rectal cancer patients without preoperative radiotherapy - a study in a Swedish rectal cancer trial of preoperative radiotherapy

<p>Abstract</p> <p>Background</p> <p>The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients.</p> <p>Methods</p> <p>PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by western blot.</p> <p>Results</p> <p>In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (<it>P </it>= 0.03). No survival relationship in patients with RT was observed (<it>P </it>= 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (<it>P </it>= 0.68)/inner tumour area (<it>P </it>= 0.49). In patients with RT, strong PINCH expression was related to a higher grade of LVD (lymphatic vessel density) (<it>P </it>= 0.01)</p> <p>Conclusions</p> <p>PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.</p