The Compound Cryogenic Distribution Line for the LHC: Status and Prospects

After a pre-series phase qualifying the design of three European firms, CERN adjudicated end of 2001 one contract for the manufacturing and installation of the cryogenic distribution line (QRL) for the LHC (Large Hadron Collider). Each of the eight ~3.2 km QRL sectors is feeding helium at different temperatures and pressures to the local cooling loops of the strings of superconducting magnets operating in superfluid helium below 2 K. With an overall length of 25.8 km the QRL has a very critical cost to performance ratio. We present a project overview describing all phases, status and schedule

Results from the Qualification of the three Pre-series Test Cells for the LHC Cryogenic Distribution Line

Three pre-series test cells of the LHC cryogenic distribution line, manufactured by three European industrial companies, have been tested in the years 2000 and 2001 to qualify the design proposed and to verify the thermal and mechanical performances. The pre-series test cell, about 112 m long, consisted of a standard cell (about 107 m long) and an additional service module needed for test purposes. This paper summarises and compares the main results of the qualification tests to the requirements of the technical specification. Technical considerations on the measurement stability and corresponding overall error are also presented

The Cryogenic Distribution Line for the LHC: Functional Specification and Conceptual Design

The Large Hadron Collider (LHC) currently under construction at CERN will make use of superconducting magnets operating in superfluid helium below 2 K. The cryogenic distribution scheme for each of the eight sectors, individually served by a refrigeration plant, is based on a separate Cryogenic Distribution Line (QRL) feeding helium at different temperatures and pressures to the elementary cooling loops. The QRL comprises two supply headers and three return headers including a sub-atmospheric one. Low heat inleak to all temperature levels is essential for the overall LHC cryogenic performance. With an overall length of 25.6 km the QRL has a very critical cost-to-performance ratio. Therefore, following an in-house feasibility study, CERN adjudicated in autumn 1998 three industrial contracts in parallel for the supply of Pre-Series Test Cells (~ 112 m) of the QRL, which will be tested at CERN in 2000. Installation of the QRL for LHC is scheduled from 2002 to mid 2004. This paper will present the general layout, the functional requirements as well as some aspects of the in-house conceptual design

A concise synthesis of a methyl ester 2-resorcinarene: A chair-conformation macrocycle

Anions are important hydrogen bond acceptors in a range of biological, chemical, environ-mental and medical molecular recognition processes. These interactions have been exploited for the design and synthesis of ditopic resorcinarenes as the hydrogen bond strength can be tuned through the modification of the substituent at the 2-position. However, many potentially useful compounds, especially those incorporating electron-withdrawing functionalities, have not been prepared due to the challenge of their synthesis: their incorporation slows resorcinarene formation that is accessed by electrophilic aromatic substitution. As part of our broader campaign to employ resorcinarenes as selective recognition elements, we need access to these specialized materials. In this article, we report a straightforward synthetic pathway for obtaining a 2-(carboxymethyl)-resorcinarene, and resorcinarene esters in general. We discuss the unusual conformation it adopts and propose that this arises from the electron-withdrawing nature of the ester substituents that renders them better hydrogen bond acceptors than the phenols, ensuring that each of them acts as a donor only. Density Functional Theory (DFT) calculations show that this conformation arises as a consequence of the unusual configurational isomerism of this compound and interruption of the archetypal hydrogen bonding by the ester functionality

Thermo-responsive self-immolative nanoassemblies: Direct and indirect triggering

A thermo-responsive end-cap based on a retro-Diels-Alder and subsequent furan elimination reaction was developed. It was used to cap poly(ethyl glyoxylate), allowing end-to-end depolymerization upon thermal triggering. Using block copolymers, thermo-responsive micelles and vesicles were prepared and shown to disassemble upon heating. Thermal degradation could also be triggered indirectly by magnetic field hyperthermia after incorporation of iron oxide nanoparticles into the assemblies

Toward the synthesis of an acetal-free Tn antigen anti-cancer vaccine candidate

Cancer vaccines are a promising approach to cancer treatment by activating the immune system towards cancer cells. The challenge, however, comes with the identification of biomarkers correlated with cancer. Unfortunately, many oncotargets are simply upregulated in cancer; these are inappropriate vaccine targets as they are also present on healthy cells and therefore would ultimately initiate a very dangerous systemic immune response. In contrast, Tumor-Associated Carbohydrate Antigens (TACAs) are not found in healthy adult tissue but are found on over 90% of biopsied carcinomas. When incorporated into glycopeptides or other immunogenic scaffolds, these carbohydrate antigens have formed the basis of the development of anti-tumor immunotherapies through the induction of a specific immune response against cancer cells. However, despite promising preliminary data, none of these candidates have reached the clinic. Our hypothesis is that the carbohydrates on the vaccines may not survive antigen processing, and so more stable versions of these materials are required to create viable vaccines. Our approach is to incorporate TACAs lacking the labile glycosidic bond: acetal-free carbohydrates (AFCs). This project aims to remove the unstable acetal functional group to yield a more robust carbohydrate structure that can then be incorporated into a vaccine candidate. In this presentation, two synthetic pathways will be described: conversion of a carbohydrate to a carbasugar through a rearrangement, and de novo synthesis from noncarbohydrate materials

Tuning the hydrophobic cores of self-immolative polyglyoxylate assemblies

Polyglyoxylates are a recently-introduced class of self-immolative polymers, that depolymerize to small molecules upon the cleavage of a stimuli-responsive end-cap from the polymer terminus. The incorporation of different pendant ester groups or other aldehyde monomers offers the potential to tune the polymer properties, but this remains largely unexplored. With the goal of tuning the self-assembly and drug-loading properties of polyglyoxylate block copolymers, we explored the polymerization and copolymerization of n-butyl glyoxylate, L-menthyl glyoxylate, and chloral with ethyl glyoxylate to form UV light-responsive polyglyoxylates. The resulting polymers were coupled to poly(ethylene glycol) to afford amphiphilic block copolymers. Self-assembly of the different copolymers was studied and although each system formed solid particles, the cores of the assemblies differed in their stability, hydrophobicity, and their ability to load the hydrophobic drug celecoxib. All systems depolymerized and released the drug in response to UV light. The toxicity profiles for the assemblies were also evaluated using MDA-MB-231 cells. Overall, this work demonstrates that the properties of polyglyoxylates and their assemblies can be readily tuned through the incorporation of new monomers, thereby providing a promising platform for drug delivery and other applications

Polyisobutylene-paclitaxel conjugates with pendant carboxylic acids and polystyrene chains: Towards multifunctional stent coatings with slow drug release

Drug-eluting stents are used in the treatment of atherosclerosis, where the incorporation of anti-proliferative or anti-inflammatory drugs decreases the rate of restenosis, the recurrence of artery narrowing. However, these stents can suffer from limitations such as drug depletion and delamination of the drug-eluting coating from the stent surface. Described here is an approach aimed at addressing these issues. Starting from a maleic anhydride adduct of polyisobutylene (PIB) prepared from butyl rubber, ring opening using paclitaxel (PTX) or a combination of PTX and polystyrene (PS) afforded covalent conjugates of PTX and PIB or PIB-PS graft copolymers bearing pendant carboxylic acids. When coated on stainless steel, the drug release was slower than that from a control coating that ressembles a clinical formulation comprising a physical mixture of a PS-PIB-PS triblock copolymer (SIBS) and PTX. The PTX conjugates also exhibited enhanced adhesion to stainless steel and increased tensile strength in comparison with the starting rubber. Cytotoxicity assays indicated that the materials did not leach toxic levels of PTX into cell culture media. Nevertheless, they were capable of inhibiting the adhesion and proliferation of C2C12 cells on their surfaces. These properties are advantageous for the potential application of the materials as stent coatings

Reaction of Alkynyl- And Alkenyltrifluoroborates with Propargyldicobalt Cations: Alkynylation, Alkenylation, and Cyclopropanation Product Pathways

The Lewis acid-mediated Nicholas reactions of propargyl acetate–Co2(CO)6 complexes with a series of potassium alkynyltrifluoroborates and potassium alkenyltrifluoroborates are described. Alkynyltrifluoroborates directly alkynylate the intermediate propargyldicobalt cations. In contrast, alkenyltrifluoroborates proceed through one of the three modes of dominant reactivity: C-2-substituted alkenyltrifluorobrates directly alkenylate, predominantly with the retention of stereochemistry. C-1-substituted alkenyltrifluoroborates alkenylate at C-2. Potassium vinyltrifluoroborate incorporates a cyclopropane at the site propargyl to alkynedicobalt. Computational analysis of these systems explains the differential modes of reactivity of alkenyltrifluoroborates and outlines the probable mechanisms for the formation of each product

The Cryogenics of the LHC Interaction Region Final Focus Superconducting Magnets

The LHC interaction region final focus magnets will include four superconducting quadrupoles cooled with pressurized, static superfluid helium at 1.9 K. The heat absorbed in pressurized He II, which m ay be more than 10 Watts per meter due to dynamic heating from the particle beam halo, will be transported to saturated He II at 1.8 K and removed by the 16 mbar vapor. This paper discusses the concep tual design for the cryogenics of the interaction region final focus superconducting magnets and the integration of this magnet system into the overall LHC cryogenic system