Application of Petrov-Galerkin methods to transient boundary value problems in chemical engineering: adsorption with steep gradients in bidisperse solids

Petrov-Galerkin methods are known to be versatile techniques for the solution of a wide variety of convection-dispersion transport problems, including those involving steep gradients. but have hitherto received little attention by chemical engineers. We illustrate the technique by means of the well-known problem of simultaneous diffusion and adsorption in a spherical sorbent pellet comprised of spherical, non-overlapping microparticles of uniform size and investigate the uptake dynamics. Solutions to adsorption problems exhibit steep gradients when macropore diffusion controls or micropore diffusion controls, and the application of classical numerical methods to such problems can present difficulties. In this paper, a semi-discrete Petrov-Galerkin finite element method for numerically solving adsorption problems with steep gradients in bidisperse solids is presented. The numerical solution was found to match the analytical solution when the adsorption isotherm is linear and the diffusivities are constant. Computed results for the Langmuir isotherm and non-constant diffusivity in microparticle are numerically evaluated for comparison with results of a fitted-mesh collocation method, which was proposed by Liu and Bhatia (Comput. Chem. Engng. 23 (1999) 933-943). The new method is simple, highly efficient, and well-suited to a variety of adsorption and desorption problems involving steep gradients. (C) 2001 Elsevier Science Ltd. All rights reserved.

Synthesis of an analog of the thyroid hormone-binding protein transthyretin via regioselective chemical ligation

Transthyretin is an essential protein responsible for the transport of thyroid hormones and retinol in human serum and is also implicated in the amyloid diseases familial amyloidotic polyneuropathy and senile systemic amyloidosis. Its folding properties and stabilization by ligands are of current interest due to their importance in understanding and combating these diseases, Here we report the solid phase synthesis of the monomeric unit of a transthyretin analog (equivalent to 127 amino acids) using t-Boc chemistry and peptide ligation and its folding to form a functional 54-kDa tetramer, The monomeric unit of the protein was chemically synthesized in three parts (positions 1-51, 54-99, and 102-127) and ligated using a chemoselective thioether ligation chemistry. The synthetic protein was folded and assembled to a tetrameric structure in the presence of transthyretin's native ligand, thyroxine, as shown by gel filtration chromatography, native gel electrophoresis, transthyretin antibody recognition, and thyroid hormone binding. Other folding products included a high molecular weight aggregate as well as a transient dimeric species. This represents one of the largest macromolecules chemically synthesized to date and demonstrates the potential of protein chemical synthesis for investigations of protein-ligand interactions.

Development of response-selective agonists of human C5a anaphylatoxin: Conformational, biological, and therapeutic considerations

Numerous studies on the relationship between the structure and function of peptide agonists derived from the biologically active, C-terminal region of human C5a anaphylatoxin have been reported over the past decade. These studies have been performed with the objective of parlaying this structure-function information into the design of peptide/peptidomimetic modulators of C5a receptor (C5aR)-mediated function. In this review, we describe a rational approach for the development of conformationally biased, decapeptide agonists of C5a and described how these stabilized and specific conformational features relate to the expression of specific C5a-like activities in vitro and in vivo. The therapeutic potential of such response-selective C5a agonists is discussed and underscored by the results of one such response-selective C5a agonist that was used in vivo as an effective molecular adjuvant capable of generating antigen-specific humoral and cellular immune responses. Finally, we describe the synthesis of a new generation of highly response-selective, conformationally biased C5a agonist and discuss the in vitro and in vivo biologic results that so indicate this biologic selectivity.

Induction of immune tolerance by dendritic cells: implications for preventative and therapeutic immunotherapy of autoimmune disease

Dendritic cells (DC) have a key role in controlling the immune response, by determining the outcome of antigen presentation to T cells. Through costimulatory molecules and other factors, DC are involved in the maintenance of peripheral tolerance through modulation of the immune response. This modulation occurs both constitutively, and in inflammation, in order to prevent autoimmunity and to control established immune responses. Dendritic cell control of immune responses may be mediated through cytokine or cell-contact dependent mechanisms. The molecular and cellular basis of these controls is being understood at an increasingly more complex level. This understanding is reaching a level at which DC-based therapies for the induction of immune regulation in autoimmunity can be tested in vivo. This review outlines the current state of knowledge of DC in immune tolerance, and proposes how DC might control both T cell responses, and themselves, to prevent autoimmunity and maintain peripheral tolerance.

Therapeutic patellar taping changes the timing of vasti muscle activation in people with patellofemoral pain syndrome

Objective: To examine the effect of the application of tape over the patella on the onset of electromyographic (EMG) activity of vastus medialis obliquus (VMO) relative to vastus lateralis (VL) in participants with and without patellofemoral pain syndrome (PFPS). Design: Randomised within subject. Settings: University laboratory. Participants: Ten participants with PFPS and 12 asymptomatic controls. Interventions: Three experimental taping conditions: no tape, therapeutic tape, and placebo tape. Main Outcome Measures: Electromyographic onset of VMO and VL assessed during the concentric and eccentric phases of a stair stepping task. Results: When participants with PFPS completed the stair stepping task, the application of therapeutic patellar tape was found to alter the temporal characteristics of VMO and VL activation, whereas placebo tape had no effect. In contrast, there was no change in the EMG onset of VMO and VL with the application of placebo or therapeutic tape to the knee in the asymptomatic participants. Conclusions: These data support the use of patellar taping as an adjunct to rehabilitation in people with PFPS.

Combined chemical separation of Lu, Hf, Sm, Nd, and REEs from a single rock digest: Precise and accurate isotope Determinations of Lu-Hf and Sm-Nd using multicollector-ICPMS

A combined procedure for separating Lu, Hf, Sm, Nd, and rare earth elements (REEs) from a single sample digest is presented. The procedure consists of the following five steps: (1) sample dissolution via sodium peroxide sintering; (2) separation of the high field strength elements from the REEs and other matrix elements by a HF-free anion-exchange column procedure; (3) purification of Hf on a cation-exchange resin; (4) separation of REEs from other matrix elements by cation exchange; (5) Lu, Sm, and Nd separation from the other REEs by reversed-phase ion chromatography. Analytical reproducibilities of Sm-Nd and Lu-Hf isotope systematics are demonstrated for standard solutions and international rock reference materials. Results show overall good reproducibilities for Sm-Nd systematics independent of the rock type analyzed. For the Lu-Hf systematics, the reproducibility of the parent/daughter ratio is much better for JB-1 (basalt) than for two analyzed felsic crustal rocks (DR-N and an Archaean granitoid). It is demonstrated that this poorer reproducibility of the Lu/Hf ratio is truly caused by sample heterogeneity; thus, results are geologically reasonable.

A cassette ligation strategy with thioether replacement of three Gly-Gly peptide bonds: Total chemical synthesis of the 101 residue protein early pregnancy factor [psi(CH2S)(28-29,56-57,76-77)]

The 101 residue protein early pregnancy factor (EPF), also known as human chaperonin 10, was synthesized from four functionalized, but unprotected, peptide segments by a sequential thioether ligation strategy. The approach exploits the differential reactivity of a peptide-NHCH2CH2SH thiolate with XCH2CO-peptides, where X = Cl or I/Br. Initial model studies with short functionalized (but unprotected) peptides showed a significantly faster reaction of a peptide-NHCH2CH2SH thiolate with a BrCH2CO-peptide than with a CICH2CO-peptide, where thiolate displacement of the halide leads to chemoselective formation of a thioether surrogate for the Gly-Gly peptide bond. This rate difference was used as the basis of a novel sequential ligation approach to the synthesis of large polypeptide chains. Thus, ligation of a model bifunctional N-alpha-chloroacetyl, C-terminal thiolated peptide with a second N-alpha-bromoacetyl peptide demonstrated chemoselective bromide displacement by the thiol group. Further investigations showed that the relatively unreactive N-alpha-chloroacetyl peptides could be activated by halide exchange using saturated KI solutions to yield the highly reactive No-iodoacetyl peptides. These findings were used to formulate a sequential thioether ligation strategy for the synthesis of EPF, a 101 amino acid protein containing three Gly-Gly sites approximately equidistantly spaced within the peptide chain. Four peptide segments or cassettes comprising the EPF protein sequence (BrAc-[EPF 78-101] 12, ClAc-[EPF 58-75]-[NHCH2CH2SH] 13, ClAc-[EPF 30-55]-[NHCH2CH2SH] 14, and Ac-[EPF 1-27]-[NHCH2CH2SH] 15) of EPF were synthesized in high yield and purity using Boc SPPS chemistry. In the stepwise sequential ligation strategy, reaction of peptides 12 and 13 was followed by conversion of the N-terminal chloroacetyl functional group to an iodoacetyl, thus activating the product peptide for further ligation with peptide 14. The process of ligation followed by iodoacetyl activation was repeated to yield an analogue of EPF (EPF psi(CH2S)(28-29,56-57,76-77)) 19 in 19% overall yield.

Liver transplantation as a therapeutic option for hepatocellular carcinoma

Better outcomes of the patients receiving liver transplantation for viral hepatitis and hepatocellular carcinoma (HCC) are achieved by improved patient selection and perioperative treatment with antiviral agents including lamivudine, ribavirin and interferon. Patient selection is accomplished by high-quality imaging as well as exclusion of patients with large tumors, obvious extrahepatic disease or macroscopic vascular invasion. Using such criteria, a 5-year survival of 92% has been reached in the Queensland Liver Transplant Service on a small number of highly selected patients with HCC. The treatment algorithm of Makuuchi has guided us in recommending resection, estimating to what extent the liver resection can be performed safely, and timing liver transplantation when it is the only option. Adult-to-adult living-donor liver transplantation is being performed safely in many centers worldwide. The transplantation of liver from living donors to HCC patients, when standard criteria for the likelihood of good outcomes are fulfilled, will increase in Japan in the near future. Copyright (C) 2002 S. Karger AG, Basel.

Granulomatous meningoencephalomyelitis in dogs

Granulomatous meningoencephalomyelitis (GME) is a morphological description of an inflammatory disorder of the canine central nervous system (CNS). It has been reported in many areas of the world. including Australia, and is one of the more common nervous disorders of dogs. Most breeds of dogs of both sexes and all ages can be affected but young to middle-aged small and terrier breeds have been stated as being more susceptible. There are variable anatomical forms and distribution of the lesions in the CNS; the presenting clinical signs can reflect singly or collectively cerebellar, cerebral, and brain stem dysfunction. Meningeal and spinal cord involvement are also common. There is no specific diagnostic test but a combination of clinical signs, history and cerebro-spinal fluid cytology are useful indicators. However differential diagnosis from other inflammatory disorders of the brain is difficult. No infectious agent aetiology has been established for GME and therefore no satisfactory therapeutic approach is available. The role of the immune system in terms of either initiating or potentiating the lesions in the CNS appears to be the most likely direction for further investigation into the nature of this disorder.

QCD thermal phase transition in the presence of a small chemical potential

We propose a new method to investigate the thermal properties of QCD with a small quark chemical potential mu. Derivatives of quark and gluonic observables with respect to mu are computed at mu=0 for two flavors of p4 improved staggered fermions with ma=0.1,0.2 on a 16(3)x4 lattice, and used to calculate the leading order Taylor expansion in mu of the location of the pseudocritical point about mu=0. This expansion should be well behaved for the small values of mu(q)/T(c)similar to0.1 relevant for BNL RHIC phenomenology, and predicts a critical curve T-c(mu) in reasonable agreement with estimates obtained using exact reweighting. In addition, we contrast the case of isoscalar and isovector chemical potentials, quantify the effect of munot equal0 on the equation of state, and comment on the complex phase of the fermion determinant in QCD with munot equal0.