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Atropisomeric molecules are a privileged class of stereogenic material that have important applications in catalysis, materials science and medicines. To date, the majority of work has been focused upon biaryl and heterobiaryl scaffolds involving restricted rotation between a pair of cyclic fragments, but C–N atropisomeric molecules based upon amines and amides where the nitrogen atom is not part of a ring system are rapidly emerging as an important class of stereogenic molecules. This is the focus of this Short Review article, which begins by discussing the factors which influence the configurational stability of such molecules and provides a historical background to their synthesis. This is followed by a detailed discussion of state-of-the-art catalytic asymmetric strategies that are now available to access C–Nacyclic atropisomers including carboxamides, sulfonamides, sulfinamides, phosphamides and diarylamines. A variety of different synthetic approaches are discussed including kinetic resolution/desymmetrization, amination, C–H functionalization, N-functionalization, and annulation.

In both library reference work and dementia care, communication between personnel and service recipients can be both complex and complicated. Professionals in both fields have therefore developed protocols and standards to assist personnel in handling these interactions. In this article we detail an exploratory comparative study that used an ethic of care framework to compare prominent guidelines for reference librarians (American Library Association’s Reference and User Services Association’s Guidelines for behavioral performance of reference and information service providers) with guidelines for workers in long-term dementia care settings (the National Institute for Health and Care Excellence’s Guideline on supporting people with dementia and their carers in health and social care). We explored how both sets of Guidelines frame the act of communication as a combination of regulated procedure and empathetic discourse to determine how the similarities among and differences between these two guidelines provide useful insights into each other. Our examination was structured using an ethic of care lens, which emphasizes the importance of interpersonal relationships, reciprocity, and empathetic benevolence. Using specific phrases in each set of Guidelines that align with and are evidence of Tronto’s four moral principles of care, we ultimately discovered, in both sets of Guidelines, an underlying ethic of care: a repeated insistence upon embedding procedures within behaviour that manifests attentiveness, responsibility, responsiveness, and competence.

Landslides in Hong Kong are commonly thought of as being fast moving with complete detachment of materials. However, following a recent hill fire, extensive ground deformation was exposed, predominantly in the form of surface cracks, associated with a slow moving landslide in an area of natural terrain above Tuen Mun, western Hong Kong. Mapping of these structures determined their extent, form and kinematics. In addition, a limited ground investigation including inclinometer monitoring was carried out to determine the depth, extent and approximate timing of deformation.

Hong Kong lies on the SE margin of the Cathaysia Block and straddles the NE-trending Lianhuashan Fault Zone, one of the dominant structural features of SE China. Isotope signatures of the Mesozoic granites have indicated that the zone overlies a major crustal discontinuity. The proposed gravity model of Hong Kong consists of a heterogeneous upper crust underlain by middle to lower crust composed of a felsic Archaean segment, approximately 25 km wide, flanked by more mafic Proterozoic crust. The southern boundary of the felsic segment dips steeply to the north, whereas the northern boundary is subvertical. Euler gravity anomalies define the fundamental faults in the upper crust, and many of these can be correlated with faults that have been mapped at surface. The middle to lower crustal discontinuities are considered to be associated with a major shear zone within the Cathaysia Block that has similar dimensions to transcratonic structures in other Precambrian shield areas. The geological development of Hong Kong and neighbouring SE China has largely been controlled by periodic reactivation of this deep crustal shear zone since the late Neoproterozoic.

Middle Jurassic to Lower Cretaceous intermediate to silicic plutonic and volcanic rocks of Hong Kong record a transition from calc-alkaline, through high-K calc-alkaline, to transitional shoshonitic compositions with time. Close spatial and temporal associations among comagmatic volcanic-plutonic pairs indicate that magmatism occurred in discrete episodes, mostly of less than one million years duration. Synchronous high-K calc-alkaline and transitional shoshonitic magmatic activity during at least one pulse suggests a relatively rapid transition from a subduction-related to an extension-related tectonic setting. Geochemical signatures indicate that the magmatic suites have a mantle origin with a decreasing crustal contribution from two distinct sources. The earliest mantle-derived magmas interacted strongly with a dominantly Archaean crustal protolith. Younger magmas show evidence for interaction with a dominantly Proterozoic crustal protolith. The strongest mantle influence is shown by magmas which were intruded along the boundary between the two dominant crustal sources. This interface marks a deep crustal discontinuity which promoted the passage of magmas to the surface.

Most rain-induced landslides on Hong Kong’s volcanic rocks are shallow and small-scale. However, two major landslides that occurred on Hong Kong Island in 1995 highlight relationships between primary volcanic foliations and kaolin accumulations that may have general significance in determining loci of larger failures. In the first case, a bedding-parallel shear zone was the locus for kaolin concentration in a shallowly dipping tuff. This formed a weak, planar, low-permeability layer which acted as the surface of rupture of a translational failure. In the second case, steeply inclined fabrics (eutaxitic foliations) and subparallel, closely spaced joints occurred within a zone of syn-volcanic folding and shearing. Deep weathering developed along the zone, with kaolin concentrations present mainly above the soil-rock interface. The irregular and variably concave to planar rupture surface was closely associated with kaolin-infilled relict joints towards the base of the soil profile. Kaolin distribution is largely associated with the weathering profile, and may have been both physically and chemically redistributed within it. Halloysite is more abundant than kaolinite in most clay samples at and near both rupture zones, and may have developed from kaolinite in response to strain. Detailed mapping of volcanic fabrics around the major landslides suggests that kaolinized bedding-parallel shear zones are uncommon, but that deep weathering zones associated with shearing and faulting are common, mappable features.

Middle Jurassic to Lower Cretaceous silicic volcanic rocks and granitoid plutons in Hong Kong form part of the broad, NE-trending Yanshanian tectonomagmatic belt, that extends through SE China. Pyroclastic deposits in Hong Kong are typically proximal and infill linear flared vents and ellipsoidal calderas. These pass down through elongate rift-like conduits into extensive multiple fault- and shear zone-hosted (9sheeted9) dyke complexes and granitoid plutons. Dykes also emphasize the limits of calderas. The spatial distribution and geometry of the vents, calderas, dykes and plutons are structurally controlled during each of four temporally well-constrained periods of petrogenetically related volcanism and plutonism. E- and ENE-trending axes of extension, and transtension were dominant. NW-trending faults increased in importance with time, and their intersections with ENE-trending faults influenced the loci of volcanic centres. Nesting of the calderas confirms persistent reactivation of some faults. The loci of magmatism migrated over 25 Ma from NW to SE. Zones of silicic crust created during these magmatic episodes have a broadly tripartite crustal 9stratigraphy9 (pluton, dyke, volcanic) reminiscent in very general terms of ophiolites. The zones were created during periods of unusually rapid extension, as the continental margin of SE China changed from an active margin, dominated by subduction, to a back-arc regime, and dextral strike-slip along ENE-trending faults gave way to sinistral strike-slip.

Bovine tuberculosis is a threat to animal and human health in several countries. Greater understanding of the immunology of the disease is required to develop improved tests and vaccines. This study has used a model of bovine tuberculosis, established in the natural host, to investigate the dynamic changes that occur in the circulating T-cell subpopulations after infection. When the phenotypic composition of the peripheral blood lymphocytes was determined pre- and post-experimental infection, the response to disease comprised three phases. Firstly, the WC1/gamma delta T cells decreased and then increased, suggesting localization to developing lesions and clonal expansion. Secondly, the CD4:CD8 ratio increased. Thirdly, the CD4:CD8 ratio decreased to less than pre-infection measurements. The latter changes suggested sequential involvement of CD4 and then CD8 T cells. The proportion of cells expressing interleukin-2 receptor (IL-2R) also increased. Panels of T-cell clones were established at various stages post-infection and all clones that exhibited antigen responsiveness were phenotyped. T-cell clones from early infection were WC1/gamma delta and CD4 in phenotype, while CD8 clones appeared later in infection, eventually becoming dominant. Therefore, from in vivo and in vitro evidence, it was suggested that there is a dynamic progression in the T-cell subpopulations involved dominantly in responses to mycobacteria.

Bound antibodies can modulate antigen processing but it is not clear to what extent this affects antigen presentation. Here we show that presentation of T cell determinants in tetanus toxin can be either enhanced or suppressed as a direct consequence of antibody modulation of antigen processing in human B lymphoblastoid cells. Remarkably, a single bound antibody or its Fab fragment can simultaneously enhance the presentation of one T cell determinant by more than 10-fold while strongly suppressing the presentation of a different T cell determinant. Biochemical analysis demonstrates that both the suppressed and boosted determinants fall within an extended domain of antigen stabilized or "footprinted" by this antibody during proteolysis. These results demonstrate that bound antibodies can modulate the capture of peptides by class II major histocompatibility complex (MHC), thus manipulating the T cell response towards or away from particular determinants. Altered processing of protein-protein complexes leading to enhanced loading of class II MHC and substantially lowered threshold for T cell activation suggests a novel mechanism that might reveal "cryptic" self determinants.

In order for silahydrocarbons to qualify, for use in a broad range of applications (automotive, aerospace, and industrial), the formulated fluid must have good oxidative stability and lubricity. This paper compares the response of a silahydrocarbon, a synthetic hydrocarbon, and a mineral oil to various antiwear and antioxidant additives. A merit rating system is described: it provides a relative ranking of the different formulated fluids according to performance.

A fining-upward, siliciclastic sequence of Wenlock strata, coarsely rudaceous at the base, infilled a canyon, about 4.5 km wide and 1700 m deep, in older strata. The rudaceous deposits, at the flat base of the canyon, are composed mainly of rounded cobbles and boulders of acid volcanic rocks. These are interpreted as cohesionless debris-flow deposits that were succeeded by northward-directed high concentration turbidity currents. The infill is deduced to have been derived from a terrain of acid volcanic rocks to the south, similar in Nd isotope composition to the Llewelyn Volcanic Group of Snowdonia. It implies mid-Silurian uplift and erosion of the Harlech Dome.

The Lower Rhyolitic Tuff Formation of Ordovician age in North Wales records the collapse, infilling, and subsequent resurgence of a volcanic caldera with an original diameter of about 15 km. This volcanic center controlled patterns of volcaniclastic sedimentation, providing enough topographic relief for both a shallow-lagoon depositional basin within the caldera and a source of sediment derived from the rim. Within the caldera, sediment consists of tuffaceous laminated siltstone and immature, coarse-grained, volcaniclastic sandstone containing plane beds, ripple cross-laminations, symmetrical wave ripples, and hummocky cross-stratification. Coarse-grained, matrix-supported, conglomerate layers and layers of ash-flow tuffs are also present. These sediments accumulated in shallow water above fair-weather wave base. Conglomerate units represent debris flows from the caldera rim, a nearby shoreline, and elevated areas associated with resurgent domes. Sedimentation outside of the caldera consisted of deposition of background suspension and volcanic-ash suspension, and turbidite deposition on a pyroclastic apron. The outer margin of the apron was dominated by fine-grained suspension and turbidite deposition, whereas the inner margin of the apron contains hummocky cross-stratification and other evidence of reworking by episodic storm waves. Local highs with associated shallow-water sedimentation existed outside the caldera. Even though deposited in high-energy marine environments, all sedimentary rocks are both texturally and mineralogically very immature. This textural immaturity differs from the typical very mature marine sediments and was caused by rapid depositional rates and a local volcanic sediment source.

Dehydroquinase, the third enzyme of the shikimate biosynthetic pathway, is inactivated by iodoacetate. Iodoacetate behaves as an affinity label for the Escherichia coli enzyme with a Ki of 30 mM and a limiting inactivation rate of 0.014 min-1 at pH 7.0 and 25 degrees C. Affinity labeling is mediated by the negative charge of the reagent since iodoacetamide does not inactivate the enzyme. 2.1-2.3 mol of carboxymethyl groups are incorporated per mol of protein monomer resulting in 90% inactivation of enzymic activity. The majority of the bound label (80%) is split equally between 2 methionine residues, Met-23 and Met-205, which were identified by sequencing radiolabelled peptide fragments isolated after proteolytic digestion. An equilibrium mixture of the substrate (dehydroquinate) and product (dehydroshikimate) substantially reduces the inactivation rate and specifically decreases the incorporation of label at both of these site, implicating them as being in or near the active site of the enzyme. Sequence alignments with other biosynthetic dehydroquinases show that of the 2 methionine residues only Met-205 is conserved. N-terminal alignments of all the available dehydroquinase sequences (both catabolic and biosynthetic classes) revealed that Met-23, although itself not conserved, resides within a cluster of conserved sequence which may constitute part of the dehydroquinate binding site. A consensus sequence was derived from these alignments and used to probe the protein sequence data banks. A related sequence was found in dehydroquinate synthase, the enzyme which precedes dehydroquinase in the shikimate pathway. These results suggest that we have identified part of the dehydroquinate binding site in both enzymes.

The second messenger phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] is generated by the action of phosphoinositide 3-kinase (PI 3-kinase), and regulates a plethora of cellular processes. An approach for dissecting the mechanisms by which these processes are regulated is to identify proteins that interact specifically with PtdIns(3,4,5)P(3). The pleckstrin homology (PH) domain has become recognized as the specialized module used by many proteins to interact with PtdIns(3,4,5)P(3). Recent work has led to the identification of a putative phosphatidylinositol 3,4,5-trisphosphate-binding motif (PPBM) at the N-terminal regions of PH domains that interact with this lipid. We have searched expressed sequence tag databases for novel proteins containing PH domains possessing a PPBM. Surprisingly, many of the PH domains that we identified do not bind PtdIns(3,4,5)P(3), but instead possess unexpected and novel phosphoinositide-binding specificities in vitro. These include proteins possessing PH domains that interact specifically with PtdIns(3,4)P(2) [TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns4P [FAPP1 (phosphatidylinositol-four-phosphate adaptor protein-1)], PtdIns3P [PEPP1 (phosphatidylinositol-three-phosphate-binding PH-domain protein-1) and AtPH1] and PtdIns(3,5)P(2) (centaurin-beta2). We have also identified two related homologues of PEPP1, termed PEPP2 and PEPP3, that may also interact with PtdIns3P. This study lays the foundation for future work to establish the phospholipid-binding specificities of these proteins in vivo, and their physiological role(s).

Infection of human cartilage with HIV in vivo has not previously been reported. Specimens of articular cartilage taken at postmortem from ten patients who were HIV-positive were examined. Two had AIDS and eight were believed to have stage-2 disease. The standard polymerase chain reaction (PCR) protocol was modified to allow semiquantitative analysis of the samples. Oligonucleotide primers labelled with 32P gamma-ATP were used to detect a segment of HIV DNA and a control DNA gene segment (HLA genome) to estimate the ratio of infected cells. The 32P-labelled PCR products were separated on acrylamide gels and visualised directly by autoradiography and computer densitometry. Infection of human cartilage in vivo was demonstrated in nine of the ten samples in which the PCR analysis was positive. The other did not react sufficiently to produce detectable radiolabelled PCR product despite repeated DNA digestion and extraction. Cartilage infected with HIV could be a potential source of HIV when used in operations.

Pigmentary glaucoma results from zonular-pigment dispersion, primarily in young, myopic, white individuals. The concavity of the midperipheral iris allows iridozonular contact. Released pigment is carried to the trabecular meshwork where it resides: (1) benignly, not affecting the intraocular pressure, as in pigment dispersion syndrome; or (2) malignantly, elevating the intraocular pressure, as in pigmentary glaucoma. Small amounts of pigment are quickly phagocytized. If the particulate load is heavy, the cells migrate further along the outflow pathway. The flattening of the iris in pigmentary glaucoma patients receiving iridotomies, along with the backward flow of pigment observed during treatment, demonstrates a greater pressure in the anterior than the posterior chamber. This reverse pupillary block may be due to temporary ocular deformations caused by blinking, as small aqueous aliquots are forced into the anterior chamber. Flattening of the concave iris is the key to current and future management of these patients.

The protozoan parasite Leishmania mexicana secretes a heavily glycosylated 100-kDa acid phosphatase (sAP) which is associated with one or more polydisperse proteophosphoglycans. Most of the glycans in this complex were released using mild acid hydrolysis conditions that preferentially cleave phosphodiester linkages. The released saccharides were shown to consist of monomeric mannose and a series of neutral and phosphorylated glycans by Dionex high performance liquid chromatography, methylation analysis, exoglycosidase digestions, and one-dimensional 1H NMR spectroscopy. The neutral species comprised a linear series of oligosaccharides with the structures [Man alpha 1-2]1-5Man. The phosphorylated oligosaccharides were characterized as PO4-6Gal beta 1-4Man and PO4-6[Glc beta 1-3]Gal beta 1-4Man. The attachment of these glycans to the polypeptide backbone via the linkage, Man alpha 1-PO4-Ser, is suggested by: 1) the finding that more than 60% of the serine residues in the polypeptide are phosphorylated and 2) the resistance of the phosphoserine residues to alkaline phosphatase digestion unless the sAP was first treated with either mild acid (to release all glycans) or jack bean alpha-mannosidase (to release neutral mannose glycans). Analysis of the partially resolved components of the complex indicated that the most of the O-linked glycans on the 100-kDa phosphoglycoprotein comprised mannose and the mannose-oligosaccharides. In contrast the major O-linked glycans on the proteophosphoglycan were short phosphoglycan chains, containing on average two repeat units per chain. In addition to the O-linked glycans, both components in the sAP complex contained N-linked glycans. The N-glycanase F-released glycans were characterized by Bio-Gel P4 chromatography and exoglycosidase digestions to be the biantennary oligomannose type with the structures Glc1Man6GlcNAc2 and Man6GlcNAc2. The O-linked glycans of the sAP complex are similar to those found in the phosphoglycan chains of the abundant surface lipophosphoglycan, but differ in having much shorter phosphoglycan chains and a more diverse series of mannose cap oligosaccharides. These data suggest that there are marked differences in the ability of different glycosyltransferases to utilize peptide-linked versus glycolipid-linked acceptors.

The p53 tumor suppressor protein is tightly regulated in the cell and is phosphorylated at multiple sites by several different protein kinases. We have investigated the phosphorylation of p53 by mitogen-activated protein (MAP) kinase, a protein kinase that plays a central role in mediating many mitogenic and differentiation signals. Recombinant wild-type mouse p53 was phosphorylated in vitro by activated recombinant p42-MAP kinase but not by inactive MAP kinase or by the activating protein, MAP kinase kinase. Phosphorylation of p53 by MAP kinase occurred at two N-terminal sites, threonine residues 73 and 83. Tryptic phosphopeptides of recombinant p53 phosphorylated in vitro by MAP kinase comigrated on two-dimensional maps with p53 from SV3T3 cells labeled in vivo with [32P]orthophosphate, suggesting that MAP kinase targets a site in p53 that is phosphorylated in the cell. Following serum stimulation of quiescent C57MG cells, two p53 kinases, which were resolved by chromatography on Mono Q, were stimulated 15-20-fold within 5 min. Each of these kinase activities co-eluted with myelin basic protein kinase activity and could be inactivated following treatment with protein phosphatase 2A, a serine/threonine phosphatase, or leukocyte antigen receptor, a protein tyrosine phosphatase, suggesting that these activities were members of the MAP kinase family. The two kinase activities from the lysates targeted the same phosphorylation sites on p53 as the purified recombinant MAP kinase. These protein kinase activities were also stimulated following exposure of the cells to ultraviolet radiation, but with slightly delayed kinetics. Phorbol ester treatment of SV3T3 cells led to increased phosphorylation of the peptide containing the residues targeted by MAP kinase. The data suggest that p53 may be phosphorylated by MAP kinase physiologically and that this interaction may be involved in the cell's response to UV exposure, growth factor stimulation, or transformation by oncogenes.

Wild-type mouse p53, expressed in Escherichia coli, was phosphorylated by highly purified casein kinase I (CKI) from rabbit muscle. The major site of phosphorylation in the p53 was identified as serine 6, which is known to be phosphorylated in vivo. Serines 4 and 9 were also phosphorylated. To determine whether CKI is likely to be a physiological p53 kinase, SV3T3 cell lysates were fractionated on a Mono Q column and assayed for p53 kinase and casein kinase activities. Four p53 kinase activities were detected, one of which co-purified with CKI activity. This p53 kinase (designated PK270) further co-purified with CKI on sucrose gradients and had a native molecular weight, like CKI, in the range of 35,000-45,000. However, PK270 was separated from the bulk of CKI activity on a phosvitin-Sepharose affinity column, and was therefore likely to be a CKI-related kinase. In support of these conclusions, phosphorylation of p53, by both CKI and PK270, was inhibited by a peptide corresponding to a consensus CKI target sequence, but not by a non-specific peptide. Moreover, phosphopeptide analyses of p53 phosphorylated by CKI or by PK270 gave similar results, indicating that these two kinases phosphorylate the same sites in p53.

Dehydroquinase, the third enzyme of the shikimate biosynthetic pathway, is inactivated by iodoacetate. Iodoacetate behaves as an affinity label for the Escherichia coli enzyme with a Ki of 30 mM and a limiting inactivation rate of 0.014 min-1 at pH 7.0 and 25 degrees C. Affinity labeling is mediated by the negative charge of the reagent since iodoacetamide does not inactivate the enzyme. 2.1-2.3 mol of carboxymethyl groups are incorporated per mol of protein monomer resulting in 90% inactivation of enzymic activity. The majority of the bound label (80%) is split equally between 2 methionine residues, Met-23 and Met-205, which were identified by sequencing radiolabelled peptide fragments isolated after proteolytic digestion. An equilibrium mixture of the substrate (dehydroquinate) and product (dehydroshikimate) substantially reduces the inactivation rate and specifically decreases the incorporation of label at both of these site, implicating them as being in or near the active site of the enzyme. Sequence alignments with other biosynthetic dehydroquinases show that of the 2 methionine residues only Met-205 is conserved. N-terminal alignments of all the available dehydroquinase sequences (both catabolic and biosynthetic classes) revealed that Met-23, although itself not conserved, resides within a cluster of conserved sequence which may constitute part of the dehydroquinate binding site. A consensus sequence was derived from these alignments and used to probe the protein sequence data banks. A related sequence was found in dehydroquinate synthase, the enzyme which precedes dehydroquinase in the shikimate pathway. These results suggest that we have identified part of the dehydroquinate binding site in both enzymes.

The Sm-Nd technique has been successfully used to date scheelites from lode gold and tungsten deposits in the Archean Midlands greenstone belt, Zimbabwe. Two phases of mineralization have been established which correlate with Late Archean and Early Proterozoic magmatic events in the region. The gold deposits are mainly structurally controlled and are spatially associated with high strain zones and internal synvolcanic to late-tectonic tonalite plutons. Most gold-bearing structures can be categorized into one of two preferred orientations: parallel to acutely oblique with the main S1 fabric, or crosscutting S1 at a high angle and striking parallel to locally developed D2 structures or fabrics. Sm-Nd dating of scheelite demonstrates that these two structural populations are characterized by discrete phases of gold mineralization. The main S1-parallel gold deposition, dated at 2.66 ± 0.05 Ga, correlates with the Late Archean trondhjemite-tonalite-granodiorite event in Zimbabwe. The S1 discordant phase has yielded an age of 2.41 ± 0.07 Ga, broadly corresponding to the timing of emplacement of the Great Dyke and reactivation of the Late Archean high-strain zones. Sr isotope data provide important constraints on the evolution of the hydrothermal fluids.