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O-glycosylation is a post-translational modification of proteins crucial to molecular mechanisms in health and disease. O-glycans are typically highly heterogeneous. The involvement of specific O-glycan sequences in many bio-recognition systems is yet to be determined due to a lack of efficient methodologies. We describe here a targeted microarray approach: O-glycome beam search that is both robust and efficient for O-glycan ligand-discovery. Substantial simplification of the complex O-glycome profile and facile chromatographic resolution is achieved by arraying O-glycans as branches, monitoring by mass spectrometry, focusing on promising fractions, and on-array immuno-sequencing. This is orders of magnitude more sensitive than traditional methods. We have applied beam search approach to porcine stomach mucin and identified extremely minor components previously undetected within the O-glycome of this mucin that are ligands for the adhesive proteins of two rotaviruses. The approach is applicable to O-glycome recognition studies in a wide range of biological settings to give insights into glycan recognition structures in natural microenvironments.

Position Statement\ud \ud The International Hypoglycaemia Study Group recommends that the frequency of detection of a glucose concentration

We have studied the ππ and K Mathematical expression systems centrally produced in proton proton collisions at 300 GeV/c and π+/p proton collisions at 85 GeV/c using the CERN Ω spectrometer. Clear evidence for S*/fo(975) production is observed. An analysis performed on the π+ π- mass spectrum in the 1.0 GeV region, using a coupled channel formalism, shows that it is possible to describe the S*/fo(975) effect with one single resonance once interference of the S*/fo(975) with the S-wave background is introduced. The resulting S*/fo(975) parameters are mo=979±4MeV, gπ=0.28±0.04, gK=0.56±0.18 corresponding to a pole position on sheet II at (1001±2)-i(36±4) MeV. Evidence is also found for a structure having a mass of 1472±12 MeV and a width of 195±33 MeV. © 1991 Springer-Verlag.

We have studied the ππ and K K ̄ systems centrally produced in proton collisions at 300 GeV/c. Clear evidence for S*/fhook0(975) production is observed. An analysis performed on the π+π- mass spectrum in the 1.0 GeV region, using a coupled channel formalism, shows that it is possible to describe the S*/fhook0(975) effect with one single resonance, and requires interference of the S*/fhook0(975) with the S-wave background. The resulting S*/fhook0(975) parameters are m0 = 979 ± 4 MeV, gπ = 0.28 ± 0.04, gK = 0.56 ± 0.18. Evidence is found for a structure having a mass of 1472 ± 12 MeV and a width of 195 ± 33 MeV. © 1991.

The aim of this experiment is to search for non-qq mesons in the reaction pp→pf(XO)ps at 300 GeV/c incident momentum, where the XO system is a centrally produced meson. The θ/f2(1720), E/f1(1420) and a new state in the 2π+2π- channel are presented as candidate non-qq mesons. © 1990.

The reaction pp→pf(π+π-π0)ps, where the π+π-π0 system is centrally produced, has been studied at 300 GeV/c. The π+π-π0 mass spectrum shows evidence for the η, ω and a2 (1320) as well as an enhancement in the a1 (1260) region. A Dalitz plot analysis of the π+π-π0 system has been performed. The a1 (1260) parameters coming from the fit of the 1+S wave are m=1208±15 MeV and Γ=430±50 MeV. No evidence is found for the h1(1170) or h1(1380). © 1990 Springer-Verlag.

The VH specificities of two rabbit antisera raised against the H chains of two human IgM cold agglutinins were studied with the aid of proteins on which the VH sequence data are available. They were found to recognize a new VH antigen (VHMar), which may represent a subgroup of VHI. This antigen is found on anti-Ii antibodies which have cross-reactive idiotypes. It is moderately well-expressed in normal gamma globulin and strongly expressed on 8% of unselected myeloma and macroglobulinaemia proteins. There is evidence to suggest that a proportion of the cross-reactive idiotypes among the anti-Ii antibodies involve this VH antigen.

In a search for glueballs and exotic states decaying into baryons and antibaryons we have investigated the production of baryon antibaryon pairs produced centrally in the reactions π+/pp → π+/p(X0)p at 85 GeV/c. In particular, channels where X0 goes to {Mathematical expression} and {Mathematical expression} have been observed. No significant new structure is observed in the mass spectra. © 1987 Springer-Verlag.

Two automated systems were designed, developed, and commercially tested to accumulate blood in troughs and basins and to transport the blood (system A) and the blood and lungs (system B) through pneumatic tubes. System A picks up blood at predetermined intervals, deposits it in a holding tank, and eventually moves it into a transport truck to be hauled to a rendering plant. System B also accumulates blood and picks it up at frequent intervals. In addition, it picks up accumulated lungs, mixes them with the blood, and feeds this material into an onsite continuous rendering operation. Both systems are highly effective and reliable in handling the product and greatly reduce the pollution entering the plant effluent. After the installation of system B, total effluent pollution was reduced in a poultry processing and rendering plant by: BOD (biochemical oxygen demand), 44%; fat, 26%; and suspended solids, 24%.

An antibody dependent cellular cytotoxic (ADCC) reaction was elicited using human mixed lymphocyte cultures against coronavirus 229E-infected C-16 cells. The response was assayed in microtitre plates by radioactive chromium release. Optimal killing of target cells was achieved using cells labelled 22 h after infection. A prozone was present and the optimal dilution of sera was invariably 1:200. The majority (70%) of sera tested gave a positive ADCC response. These included all sera judged positive by ELISA, but also some which were judged negative. Two experiments using purified IgG from serum which was ADCC and ELISA positive suggested that the response is mediated by an IgG antibody and that the prozone is due to a separate serum component.

The production of ρ{variant}0 mesons in hadronic interactions is investigated at high transverse momentum (pT > 2 GeV/c). The data come from a sample of π-N interactions at 300 GeV/c obtained at the CERN Omega Spectrometer, requiring at ρ{variant}0→π+π- with pT(pair) > 2 GeV/c to recoil against an opposite particle with pT (opposite) > 1 GeV/c. The signal/(signal + background) ratio of ρ{variant}0 production shows an increase of 38% as ξE = pT (opposite)/pT (pair) decreases from 0.5

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Background Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. Methods We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. Results Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. Conclusions In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)

A simple route for the synthesis of a monomer containing a diazoketone functionality and two disulfonyl chloride groups has been developed. Polymerization of this monomer by reaction with a diamine leads to the formation of a polymer in which the photoreactive group is incorporated as a side chain. The polymer can be formed as a thin film in a thin-film composite membrane. The factors that affect the interfacial polymerization, membrane morphology and performance have been systematically investigated. It was found that monomer concentration, the presence or absence of a surfactant, solvent and polymerization time are important factors in determining membrane morphology and separation/flux performance. Small molecule model reactions have been studied in order to establish the chemistry of the photochemical surface modification of diazoketones. The range of photochemical transformations of diazoketones has been broadened, potentially leading to the photochemical conversion of the surface barrier layer of the diazoketone containing thin-film composite membranes to carboxylic acid, hydroxyl, ethyl ester and suIfur-containing crown ether. A method for the preparation of specimens for surface characterization of the thin-film composite membranes by infrared spectroscopy has been developed. Surface analysis techniques, such as Attenuated Total Reflectance Fourier Transform Infrared (ATR-FT-IR) Spectroscopy and Scanning Electron Microscopy (SEM), proved to be useful in monitoring the photochemical surface modifications of the photolabile thin-film composite membranes. The performance of the initial diazoketone precursor membrane and photochemically modified membranes has been examined with a series of aqueous solutions of inorganic salts. It was found that photochemical surface modification can significantly alter the separation/flux performance of the membranes. A theoretical model that considers both diffusion- and reaction-controlled interfacial polymerization, under nonsteady-state conditions, has been developed. The model can describe the formation of both dense and porous thin films. The results predicted by the model are consistent with experimental results. The general model developed in this thesis for thin film formation by interfacial polymerization can include the special model already reported in the literature. The work conducted in this thesis significantly extends existing theories for the formation of thin films by interfacial polymerization and provides an important guide for effective control of the thickness of the surface barrier layer of thin-film composite membranes prepared by interfacial polymerization. Doctor of Philosophy (PhD)

This thesis describes a study of the photosolvolysis of N-benzoyl-5-bromo-7-nitroindoline. The investigation was instigated because N-acyl-5-bromo-7-nitroindolines have been considered as potential photoprotecting groups for the photolithographic formation of charge-mosaic membranes. However, no kinetic data, and only scant mechanistic information, has been reported for the photofragmentation process. Both absorption and emission spectra of N-benzoyl-5-bromo-7-nitroindoline were obtained. Based on the electronic spectra, it would seem that the two lowest energy singlet excited states are nearly isoenergetic and their relative energies are a function of the solvent medium. The distribution of photoproducts obtained from irradiation of N-benzoyl-5-bromo-7-nitroindoline in various solvent systems was investigated. It was shown that the photosolvolysis reaction is a function of the solvent properties. Thus 5-bromo-7-nitroindoline and benzoic acid were the only photoproducts formed in acetonitrile. In acetonitrile-water, 5-bromo-7-nitrosoindole as well as 5-bromo-7-nitroindoline and benzoic acid were identified. A correlation between solvent polarity, ET(30), and 5-bromo-7-nitrosoindole formation was observed. The mechanism of the fragmentation mode was examined. The presence of a free radical intermediate is suggested from the photoproduct distribution in tetrahydrofuran (THF). Observation of an electron spin resonance (e.s.r.) spectrum during irradiation of N-benzoyl-5-bromo-7-nitroindoline in an e.s.r. spectrometer cavity, 18_0 incorporation into benzoic acid, and a linear free energy relationship with sigma dot (σ•) corroborated the intermediacy of a free radical in the fragmentation process. Quantum yields of N-benzoyl-5-bromo-7-nitroindoline disappearance in different solvents and quenchers were measured in order to establish the reactive excited state and the effect of the medium on the efficiency of the transformation process. A solvent dependency on both the excited state lifetime and photosolvolysis reaction efficiency was noted. The results were indicative of a change in mechanism with a variation in solvent polarity and/or hydrogen bonding ability. A mechanism compatible with experimental results and applicable to previously reported N-acyl-2-nitroaniline photofragmentations is proposed. Thesis Doctor of Philosophy (PhD)

Investigations on the stability and reactions of various isomers of the benzohomotropylium/bridged [11]-annulene system are presented in this thesis. As 1,6-methano-[11]-annulenium cations are isomeric with benzohomotropylium cations in principle it is possible for these systems to be interconverted by a circumambulatory migration of the 'bridging' methano group. If this reaction were to proceed to equilibrium it would allow the examination of the thermodynamic stability of the various isomers. Homotropylium cations with two methyl groups at C8 are known to undergo facile circumambulatory rearrangements. Thus in this work the 1-hydroxy 8,8-dimethyl-2,3-benzohomotropylium and 1-hydroxy 8,8-dimethyl-4,5-benzohomotropylium cations have been prepared by protonation of the corresponding 2,3- and 4,5- benzohomotropones in FSO3H. On the basis of their 1H NMR spectra it is concluded that they can properly be regarded as homoaromatic cations. The thermal isomerizations of these cations have been studied in detail. The thermal isomerization of these cations led to the formation of a series of products but does not yield the corresponding [11]-annulenium isomer. In addition the barriers to ring inversion in these cations were found to be much lower than those of other homotropylium cations. This suggests that the former cations have a very open structure. Besides this experimental approach, the relative stability of these isomers has been explored using MNDO calculations. The calculated heats of formation (ΔHf) showed that the 1-benzohomotropylium cation is more stable than the corresponding [11]-annulenium ion by 21 kcal/mol. Thesis Master of Science (MSc)

This thesis describes an attempt to develop a potentially useful route to seven-membered carbocycles. α-Diketones and their enol ether derivatives were proposed to be suitable three-carbon cycloaddition dienophiles when complexed with a Lewis acid. Reaction with 1,3-dienes should then lead to the desired cycloheptyl system. 1H-NMR and 13C-NMR studies were used to determine the stoichiometry and charge delocalization of complexes formed between 2,3-butanedione, 1,2-cyclohexanedione, 2-methoxy-cyclohex-2-en-1-one and the Lewis acids TiCl4 and SnCl4. Observations from these studies suggested that 1,2-cyclohexanedione and 2-methoxy-cyclohex-2-en-1one could behave as substituted allyl cations when complexed with TiCl4 or SnCl4. Reaction of the 1,2-cyclohexanedione/TiCl4 and 2-methoxy-cyclohex-2-en-1one/ TiCl4 complexes with 1 ,3-butadiene gave rise to six-membered carbocycles from [4C+2C] cycloadditions. The reaction of 2,3-butanedione-mono-trimethylsilyl enol ether/TiCl4 complex with 1,3-butadiene gave a mixture of the [4C+2C] and [4C+3C] cycloaddition products. Thesis Master of Science (MSc)

This thesis describes an investigation into the effects of Lewis acid complexation on the photochemistry of α,β unsaturated carbonyl compounds. Initial studies involved the use of Nuclear Magnetic Resonance (NMR) and Ultraviolet (UV) spectroscopy in examining Lewis acid modification of the photostationary state for E/Z isomerization of various acyclic enones. The results obtained provide a good understanding of the origin of the perturbation of the photostationary state of these systems. In the course of these investigations, the question also arose as to the possible effects of complexation upon the photochemistry of cyclic enone systems where E/Z isomerization cannot occur, particularly whether this would catalyze [2+2] cycloadditions to the enone carbon/carbon double bond. Lewis acid complexed enones are widely used as activated dienophiles in Diels Alder reactions, and have been recently reported to serve as activated 'enophiles' in a photochemical dimerization of coumarin. The examination here is focused upon endo-tricyclo [5.2.1.02,6] deca-4,8-dien-3-one. (See Diagram in thesis). Reported here is a detailed investigation of the photochemistry of the AlEtCl2 complex of this compound, and the results are interpreted mechanistically. The reaction gives rise to a single product which reaches a photostationary state with the reactant complex. The isomerization is formally a [1,3] sigmatropic shift involving the isolated double bond. It seems likely however, to proceed by the formation of an allyl cation intermediate. Thesis Master of Science (MSc)

This thesis deals with 0-substituted carbenium ions. In particular, the relationship between the pattern of substitution and the nature of the charge distribution in the ion are probed by looking at the effects of systematic substituent change on bond distances. The model system employed in this investigation is the 1,3-dioxolan-2-ylium ion. A series of five ions were investigated by the preparation of single crystals which were studied using x-ray crystallography. The carbon oxygen bond distances around the five-membered dioxolanylium ring were found to be sensitive to changes in methyl substitution at position 4 of the ring. As methyl substitution at this position was increased systematically, an increase in the C4-03 carbon oxygen bond distance was observed. Changes in the substituent at position 2 of the dioxolanylium ring also had an effect on carbon oxygen bond distances but of a lesser magnitude than those brought about by methyl substitutions at position 4. The importance of these changes in structure are discussed in terms of the charge distribution in the cations. Thesis Master of Science (MSc)

The effect of a C-7 substituent on the position of the cycloheptatriene/ norcaradiene equilibrium has been investigated. For this purpose a series of monosubstituted cycloheptatrienes was prepared in which the C-7 substituent was a carbonium ion grouping. From the spectral properties of these systems, it has been concluded that proportion of the norcaradiene valence tautomer present increases as the electron withdrawing ability of the carbonium ion substituent is enhanced. From a comparison of the pmr spectra of 7-norcaradienylmethyl cations with suitable model systems it is suggested that these norcaradienes are aromatic and that they support an induced diamagnetic ring current when in a magnetic field. It would appear that this type of cyclic delocalization is enhanced by the presence of an electron defficient substituent at C-7 of a norcaradiene and possible reasons for this are discussed. The 7-norcaradienylmethyl cations underwent a thermal isomerization to give benzenoid materials at relatively low temperatures. A mechanism for this rearrangement has been proposed and the implication of these results to the general pathways involved in the rearrangements of the C8H9+ family of cations discussed. Several synthetic routes to 9-substituted-3,4-homotropylidenes were investigated. A number of new compounds were isolated and a new synthetic approach to this class of compounds is suggested. Diamagnetic susceptibility exaltations of a series of substituted cycloheptatrienes were determined and used as a criterion of aromaticity. It was concluded that cycloheptatrienes are best regarded as homoaromatic molecules. Moreover it would appear that the substantial diamagnetic susceptibility exaltations observed with these compounds are related to the bulk of a C-7 substituent. One neutral norcaradiene was examined by this technique and was found to be nonaromatic. Thesis Doctor of Philosophy (PhD)