Carbohydrate-based templates for synthetic vaccines and drug delivery

Methyl tetra-O-allyl, and tetra-O-[2-(tetrahydro-2H-pyranyl)oxy.-3-oxapentyl glucosides, and tetra-O-(cyanoethyl)galactosyl azide were converted into derivatives containing linkers with terminal carboxylic acid functionalities at the anomeric position and bearing four arms with phthaloyl- or BOC-protected terminal amino groups. These molecules were suitable for use in solid-phase peptide synthesis and for the preparation of dendrimers, containing multiple copies of peptides. (C) 2001 Elsevier Science Ltd. All rights reserved.

Identity and security in Korea

The summit meeting between the two Korean heads of state, which took place in Pyongyang in June 2000, constitutes a major turning point in the peninsula's history. As the effects of the meeting are gradually unfolding, a period of detente no longer seems impossible. But major difficulties remain unsolved and Korea will continue to be one of the world's most volatile areas. The task of this essay is to identify and analyse some of the entrenched political patterns that will challenge policy-makers in the years ahead. To do so it is necessary to portray the conflict in Korea not only in conventional ideological and geopolitical terms, but also, and primarily, as a question of identity. From such a vantage-point two components are essential in the search for a more peaceful peninsula. Substantial progress has recently been made in the first realm, the need to approach security problems, no matter how volatile they seem. in a cooperative and dialogical, rather than merely a coercive manner. The second less accepted but perhaps more important factor, revolves around the necessity to recognize that dialogue has its limits, that the party on the other side of the DMZ cannot always be accommodated or subsumed into compromise. Needed is an ethics of difference: a willingness to accept that the other's sense of identity and politics may be inherently incompatible with one's own.

An evidence-based medicine fellowship in a children's teaching hospital

This paper reports the introduction of an evidence-based medicine fellowship in a children’s teaching hospital. The results are presented of a self-reported ‘evidence-based medicine’ questionnaire, the clinical questions requested through the information retrieval service are outlined and the results of an information retrieval service user questionnaire are reported. It was confirmed that clinicians have frequent clinical questions that mostly remain unanswered. The responses to four questions with ‘good quality’ evidence-based answers were reviewed and suggest that at least one-quarter of doctors were not aware of the current best available evidence. There was a high level of satisfaction with the information retrieval service; 19% of users indicated that the information changed their clinical practice and 73% indicated that the information confirmed their clinical practice. The introduction of an evidence-based medicine fellowship is one method of disseminating the practice of evidence-based medicine in a tertiary children’s hospital.

MRI based diffusion and perfusion predictive model to estimate stroke evolution

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/-0.19 and 1.20 +/-0.36. For recovered tissue the mean values were 0.99 +/-0.25 and 1.87 +/-0.71, respectively. There was a significant difference between these two regions for both measures (P

Coupling between replication and packaging of flavivirus RNA: Evidence derived from the use of DNA-based full-length cDNA clones of kunjin virus

In order to study whether flavivirus RNA packaging is dependent on RNA replication, we generated two DNA-based Kunjin virus constructs, pKUN1 and pKUN1dGDD, allowing continuous production of replicating (wild-type) and nonreplicating (with a deletion of the NS5 gene RNA-polymerase motif GDD) full-length Kunjin virus RNAs, respectively, via nuclear transcription by cellular RNA polymerase II. As expected, transfection of pKUN1 plasmid DNA into BHK cells resulted in the recovery of secreted infectious Kunjin virions. Transfection of pKUN1dGDD DNA into BHK cells, however, did not result in the recovery of any secreted virus particles containing encapsidated dGDD RNA, despite an apparent accumulation of this RNA in cells demonstrated by Northern blot analysis and its efficient translation demonstrated by detection of correctly processed labeled structural proteins (at least prM and E) both in cells and in the culture fluid using coimmunoprecipitation analysis with anti-E antibodies. In contrast, when dGDD RNA was produced even in much smaller amounts in PKUN1dGDD DNA-transfected repBHK cells (where it was replicated via complementation), it was packaged into secreted virus particles, Thus, packaging of defective Kunjin virus RNA could occur only when it was replicated. Our results with genome-length Kunjin virus RNA and the results with poliovirus replicon RNA (C, I. Nugent et al,, J, Virol, 73:427-435, 1999), both demonstrating the necessity for the RNA to be replicated before it can be packaged, strongly suggest the existence of a common mechanism for minimizing amplification and transmission of defective RNAs among the quasispecies in positive-strand RNA viruses, This mechanism may thus help alleviate the high-copy error rate of RNA-dependent RNA polymerases.

Aluminophosphate-based mesoporous molecular sieves: Synthesis and characterization of TAPOs

Mesoporous Ti-substituted aluminophosphates (AlPOs) with a hexagonal, cubic and lamellar pore structure, characteristic of MCM-41, MCM-48, and MCM-50, respectively, were synthesized. The stability of these mesophases upon template removal was studied. The pore structures, surface properties, and local atom environments of Al, P, and Ti of the hexagonal and cubic Ti-containing mesoporous products were extensively characterized using X-ray diffraction, magic angle spinning nuclear magnetic resonance, AAS, XPS, ultraviolet–visible, and adsorption of nitrogen and water vapor techniques while the lamellar mesophase was not further characterized due to its very poor thermal stability. Ti-containing mesoporous AlPO materials show a reasonable thermal stability upon template removal, a hydrophilic surface property, and high porosity showing application potentials in catalytic oxidation of hydrocarbons.

Theoretical Underpinnings of Community-based Sentences and Custody for Young Offenders in Hong Kong

Much has been written about youth crime, justice and corrections in Hong Kong in the past three decades, in particular, about the historical roots of the youth justice system, causes of juvenile delinquency, and the outcomes of different rehabilitative programmes for young offenders. However, little is known in theory, practice and policy about how community-based and custodial sentences can achieve the goals of rehabilitation and correction for young offenders. In this paper, the author analyses the purposes of penal measures with reference to the classical theories of punishment, rather than empirical data or statistics. The author argues that a community-based sentence, in many respects, performs as or more effectively than a custodial programme in achieving the various sentencing aims.

The development and application of a novel safety-catch linker for BOC-based assembly of libraries of cyclic peptides

Cyclic peptides are appealing targets in the drug-discovery process. Unfortunately, there currently exist no robust solid-phase strategies that allow the synthesis of large arrays of discrete cyclic peptides. Existing strategies are complicated, when synthesizing large libraries, by the extensive workup that is required to extract the cyclic product from the deprotection/cleavage mixture. To overcome this, we have developed a new safety-catch linker. The safety-catch concept described here involves the use of a protected catechol derivative in which one of the hydroxyls is masked with a benzyl group during peptide synthesis, thus making the linker deactivated to aminolysis. This masked derivative of the linker allows BOC solid-phase peptide assembly of the linear precursor. Prior to cyclization, the linker is activated and the linear peptide deprotected using conditions commonly employed (TFMSA), resulting in deprotected peptide attached to the activated form of the linker. Scavengers and deprotection adducts are removed by simple washing and filtration. Upon neutralization of the N-terminal amine, cyclization with concomitant cleavage from the resin yields the cyclic peptide in DMF solution. Workup is simple solvent removal. To exemplify this strategy, several cyclic peptides were synthesized targeted toward the somatostatin and integrin receptors. From this initial study and to show the strength of this method, we were able to synthesize a cyclic-peptide library containing over 400 members. This linker technology provides a new solid-phase avenue to access large arrays of cyclic peptides.