Modeling And Analysis Of Biospecific Adsorption In A Finite Bath

A general model is presented and used to predict the dynamic behavior of the adsorption and wash stages of bio specific adsorption (affinity chromatography) in a finite bath. The model accounts for film and diffusional mass transfer resistances as well as for the rates of interaction between adsorbates and ligands. The model is applicable to single and multicomponent bio specific as well as nonspecific adsorption, and the adsorbates may be monovalent or multivalent. The predictions of the model are compared with the experimental data of the adsorption of β‐galactosidase onto immobilized anti‐β‐galactosidase. The results of bio specific adsorption of bivalent adsorbates indicate that a competition for ligands occurs between molecules forming one‐site interaction and two‐site interaction complexes. This competition can lead to the displacement of the adsorbate from the adsorbate‐ligand complex whose formation is least favored. Copyright © 1987 American Institute of Chemical Engineer

Oxygen Tension Profiles In Tumors Predicted By A Diffusion With Absorption Model Involving A Moving Free Boundary

The dynamic behavior of the oxygen tension distribution in tumors during radiotherapy is studied by the development and solution of a diffusion with absorption model involving a moving free boundary. The oxygen uptake rates within the tumor are considered to be functions of the oxygen concentration and results are presented for zeroth-, half-, first- and second-order rates of absorption, as well as when the rate of oxygen absorption is described by the Michaelis-Menten expression. The results presented in this work may be used together with the data from the oxygen radiosensitivity curve of a tumor, in order to determine the proper radiation dosage that should be applied to the tumor during radiotherapy, so as to compensate for the lost killing effectiveness resulting from oxygen consumption by the tumor. The model used in this study may also be employed in examining the role of oxygen and hypoxia in chemotherapy, when cycle-specific chemotherapeutic agents are used. The numerical procedure developed for the solution of the equations of the model may become applicable to problems encountered in such diverse areas as statistical decision theory, heat transfer with changes of phase, thermal explosions, optimal control and fluid flow in porous media. © 1988

Frontal Chromatography of Proteins: The Effect on Column Performance of the Restricted Diffusion of Molecules in Porous Chromatographic Adsorbents

A theoretical formulation is presented that can be used to describe the dynamic behavior of frontal chromatography of proteins in columns packed with adsorbent particles in which restricted pore diffusion of the adsorbate molecules occurs. The results of this work clearly indicate that the time for breakthrough and the effective utilization of the adsorptive capacity of the chromatographic particles increase as (a) the size of the adsorbate and/or ligand (active site) molecule decreases, (b) the pore connectivity, n(T), of the porous network of the adsorbent particles increases, and (c) the column length, L, increases. Copyright (C) 1998 Elsevier Science B.V

Network Model Investigation Of Gas Transport In Bidisperse Porous Adsorbents

A capillary network model consisting of a micropore network permeated by one of macropores of randomly varying size has been constructed. Although simplified (to keep computer space and time requirements low) in relation to a real bidisperse porous adsorbent or catalyst, it embodies the salient pore structural features likely to determine the gas-transport behavior of such porous solids. Suitable model calculations of Knudsen gas-phase and surface diffusion enabled us to (i) validate useful approximate methods for the more economical evaluation of network permeability and (ii) demonstrate certain important characteristic effects of nonrandom bidisperse pore structure on transport behavior and their practical consequences, especially in connection with the experimental determination of surface diffusion coefficients. © 1991, American Chemical Society. All rights reserved

Laminin β2 variants associated with isolated nephropathy that impact matrix regulation

Mutations in LAMB2, encoding laminin β2, cause Pierson syndrome and occasionally milder nephropathy without extrarenal abnormalities. The most deleterious missense mutations that have been identified affect primarily the N-terminus of laminin β2. On the other hand, those associated with isolated nephropathy are distributed across the entire molecule, and variants in the β2 LEa-LF-LEb domains are exclusively found in cases with isolated nephropathy. Here we report the clinical features of mild isolated nephropathy associated with 3 LAMB2 variants in the LEa-LF-LEb domains (p.R469Q, p.G699R, and p.R1078C) and their biochemical characterization. Although Pierson syndrome missense mutations often inhibit laminin β2 secretion, the 3 recombinant variants were secreted as efficiently as WT. However, the β2 variants lost pH dependency for heparin binding, resulting in aberrant binding under physiologic conditions. This suggests that the binding of laminin β2 to negatively charged molecules is involved in glomerular basement membrane (GBM) permselectivity. Moreover, the excessive binding of the β2 variants to other laminins appears to lead to their increased deposition in the GBM. Laminin β2 also serves as a potentially novel cell-adhesive ligand for integrin α4β1. Our findings define biochemical functions of laminin β2 variants influencing glomerular filtration that may underlie the pathogenesis of isolated nephropathy caused by LAMB2 abnormalities

R & D for collider beauty physics at the LHC

We propose an R&D program for the development of a Beauty trigger and innovative elements of the associated spectrometer. A series of short test runs is proposed at the SPS p-pbar Collider with the minimal spectrometer which will allow a credible B signal to be obtained in an invariant mass spectrum of reconstructed B mesons. The program builds on the success of the recent collider run of the P238 Collaboration, in which clean signals from beam-beam interactions were observed in a large silicon strip microvertex detector running 1.5 mm from the circulating beams. A continuing successful R&D program of the type proposed could ultimately lead to a collider experiment at the LHC to study CP Violation and rare B decays

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Introduction: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results: A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion: This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies

The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma

BACKGROUND: Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers in the phase III adjuvant radiotherapy VorteX trial. METHODS: Formalin-fixed paraffin-embedded tumour biopsies, fresh tumour/normal tissue and blood were collected before radiotherapy. Immunohistochemistry for HIF-1α, CAIX and GLUT1 was performed on tissue microarrays and assessed by two scorers (one pathologist). Prognostic analysis of disease-free survival (DFS) used Kaplan-Meier and Cox regression. RESULTS: Biobank and outcome data were available for 203 out of 216 randomised patients. High CAIX expression was associated with worse DFS (hazard ratio 2.28, 95% confidence interval: 1.44-3.59, P<0.001). Hypoxia-inducible factor-1α and GLUT1 were not prognostic. Carbonic anhydrase IX remained prognostic in multivariable analysis. CONCLUSIONS: The VorteX-Biobank contains tissue with linked outcome data and is an important resource for research. This study confirms hypoxia is linked to poor prognosis in STS and suggests that CAIX may be the best known marker. However, overlap between single marker positivity was poor and future work will develop an STS hypoxia gene signature to account for tumour heterogeneity