The Control of Public Education and School Library Media Programs

published or submitted for publicatio

The development of biomolecular Raman optical activity spectroscopy

Following its first observation over 40 years ago, Raman optical activity (ROA), which may be measured as a small difference in the intensity of vibrational Raman scattering from chiral molecules in right- and left-circularly polarized incident light or, equivalently, the intensity of a small circularly polarized component in the scattered light using incident light of fixed polarization, has evolved into a powerful chiroptical spectroscopy for studying a large range of biomolecules in aqueous solution. The long and tortuous path leading to the first observations of ROA in biomolecules in 1989, in which the author was closely involved from the very beginning, is documented, followed by a survey of subsequent developments and applications up to the present day. Among other things, ROA provides information about motif and fold, as well as secondary structure, of proteins; solution structure of carbohydrates; polypeptide and carbohydrate structure of intact glycoproteins; new insight into structural elements present in unfolded protein sequences; and protein and nucleic acid structure of intact viruses. Quantum chemical simulations of observed Raman optical activity spectra provide the complete three-dimensional structure, together with information about conformational dynamics, of smaller biomolecules. Biomolecular ROA measurements are now routine thanks to a commercial instrument based on a novel design becoming available in 2004

Assessing the Information Needs of Rural People: The Development of an Action Strategy for Rural Librarians

published or submitted for publicatio

Schizotypy: A Multi-Country Study of Psychometrics, Socio-Cultural Influences, Cognitive Processes, and Electrophysiological Markers

Schizotypy represents a latent personality organisation reflecting a putative liability for schizophrenia spectrum disorders. Schizotypic traits include anomalies in cognition (e.g., hallucinations), socio-emotional function (e.g., constricted affect), and behaviour (e.g., odd behaviour and language) that do not meet the clinical threshold for psychotic disorders. This thesis presents a series of studies investigating schizotypal measurement across ethno-cultural settings, examining cognitive antecedents and outcomes of schizotypy, and a schizotypal-continuum exploration into electrophysiological function. Studies 1-3 examined the Schizotypal Personality Questionnaire (SPQ) as a measurement tool for schizotypy. These studies re-evaluated the domain structure of the English SPQ and the German SPQ, and developed and evaluated a Malay translation of the SPQ. Further, through the evaluation and development of these measures, schizotypy was explored within the framework of ethnic and cultural identities. This included evaluations between African Caribbeans in the UK and Trinidad, with White British participants; Malay and Chinese participants in Malaysia, and; central European White participants from Austria and southern Germany, with a similar cultural (migrational) group in the UK. Studies 4a and 4b concerned schizotypy, cognitive processes, and conspiracy ideation. From an initial pilot, associations were established with conspiracy ideation, included as a prima facie outcome of disordered thinking. A follow-up study showed that analytic thinking mediated the relationship between Odd Beliefs or Magical Thinking (but not Ideas of Reference) and belief in conspiracy theories. Study 5 investigated whether a combination of high schizotypal ratings and abnormal electrophysiological function could be established. Second, this study allowed for a unique comparison between culture and ethnicity, within the assessment of electrophysiological function. Finally, this study allowed for an investigation into associations between the domains established in Study 1 (namely, Cognitive-Perceptual, Paranoid, Disorganised, and Negative) and electrophysiological function. Results indicated little evidence of association between the schizotypy and schizophrenia literature; that is, there was no apparent electrophysiological deficits for high schizotypal individuals and no ethno-cultural influence. Further, the results of the regression indicated no support for associations at the higher-order domain level and electrophysiological function. Taken together, these studies informed the schizotypal literature through multiple routes. Indeed, this thesis addressed both the personality (cognitive outcomes) and clinical (electrophysiological) nature of schizotypy with the foundation of a thorough measurement examination

Ramachandran mapping of peptide conformation using a large database of computed Raman and Raman optical activity spectra

In the past few decades, Raman optical activity (ROA) spectroscopy has been shown to be very sensitive to the solution structure of peptides and proteins. A major and urgent challenge remains the need to make detailed assignments of experimental ROA patterns and relate those to the solution structure adopted by the protein. In the past few years, theoretical developments and implementations of ROA theory have made it possible to use quantum chemical methods to compute the ROA spectra of peptides. In this work, a large database of ROA spectra of peptide model structures describing the allowed backbone conformations of proteins was systematically calculated and used to make unprecedented detailed assignments of experimental ROA patterns to the conformational elements of the peptide in solution. By using a similarity index to compare an experimental spectrum to the database spectra (2902 theoretical spectra), the conformational preference of the peptide in solution can be assigned to a very specific region in the Ramachandran space. For six (poly)peptides this approach was validated and gives excellent agreement between experiment and theory. Additionally, hydrogen/deuterium exchanged structures and the conformational dependence of the amide modes in Raman spectra can be analysed using the new database. The excellent agreement between experiment and theory demonstrates the power of the newly developed database as a tool to study Raman and ROA patterns of peptides and proteins. The interpretation of experimental ROA patterns of different proteins published in the scientific literature is discussed based on the spectral trends observed in the database

Chirality, magnetism and light

No abstract available

Giant circular dichroism of a molecule in a region of strong plasmon resonances between two neighboring gold nanocrystals

We report on giant circular dichroism (CD) of a molecule inserted into a plasmonic hot spot. Naturally occurring molecules and biomolecules have typically CD signals in the UV range, whereas plasmonic nanocrystals exhibit strong plasmon resonances in the visible spectral interval. Therefore, excitations of chiral molecules and plasmon resonances are typically off-resonant. Nevertheless, we demonstrate theoretically that it is possible to create strongly-enhanced molecular CD utilizing the plasmons. This task is doubly challenging since it requires both creation and enhancement of the molecular CD in the visible region. We demonstrate this effect within the model which incorporates a chiral molecule and a plasmonic dimer. The associated mechanism of plasmonic CD comes from the Coulomb interaction which is greatly amplified in a plasmonic hot spot.Comment: Manuscript: 4+pages, 4 figures; Supplemental_Material: 10 pages, 7 figure

Nitric Oxide Bioavailability and Its Potential Relevance to the Variation in Susceptibility to the Renal and Vascular Complications in Patients With Type 2 Diabetes

OBJECTIVE—We compared the renal and systemic vascular (renovascular) response to a reduction of bioavailable nitric oxide (NO) in type 2 diabetic patients without nephropathy and of African and Caucasian heritage. RESEARCH DESIGN AND METHODS—Under euglycemic conditions, renal blood flow was determined by a constant infusion of paraminohippurate and changes in blood pressure and renal vascular resistance estimated before and after an infusion of l-Ng-monomethyl-l-arginine. RESULTS—In the African-heritage group, there was a significant fall in renal blood flow (Δ−46.0 ml/min per 1.73 m(2); P < 0.05) and rise in systolic blood pressure (Δ10.0 mmHg [95% CI 2.3–17.9]; P = 0.017), which correlated with an increase in renal vascular resistance (r(2) = 0.77; P = 0.004). CONCLUSIONS—The renal vasoconstrictive response associated with NO synthase inhibition in this study may be of relevance to the observed vulnerability to renal injury in patients of African heritage

Biomacromolecular stereostructure mediates mode hybridization in chiral plasmonic nanostructures

The refractive index sensitivity of plasmonic fields has been exploited for over 20 years in analytical technologies. While this sensitivity can be used to achieve attomole detection levels, they are in essence binary measurements that sense the presence/absence of a predetermined analyte. Using plasmonic fields, not to sense effective refractive indices but to provide more “granular” information about the structural characteristics of a medium, provides a more information rich output, which affords opportunities to create new powerful and flexible sensing technologies not limited by the need to synthesize chemical recognition elements. Here we report a new plasmonic phenomenon that is sensitive to the biomacromolecular structure without relying on measuring effective refractive indices. Chiral biomaterials mediate the hybridization of electric and magnetic modes of a chiral solid-inverse plasmonic structure, resulting in a measurable change in both reflectivity and chiroptical properties. The phenomenon originates from the electric-dipole–magnetic-dipole response of the biomaterial and is hence sensitive to biomacromolecular secondary structure providing unique fingerprints of α-helical, β-sheet, and disordered motifs. The phenomenon can be observed for subchiral plasmonic fields (i.e., fields with a lower chiral asymmetry than circularly polarized light) hence lifting constraints to engineer structures that produce fields with enhanced chirality, thus providing greater flexibility in nanostructure design. To demonstrate the efficacy of the phenomenon, we have detected and characterized picogram quantities of simple model helical biopolymers and more complex real proteins