Synthesis of new peptide derivatives that self-assemble into nanostructured hydrogels for biomedical applications

Tese de Doutoramento em Ciências (área de especialização em Química)

Patients' Needs for Care in Public Mental Health: Unity and Diversity of Self-Assessed Needs for Care.

PURPOSE: Needs assessment is recognized to be a key element of mental health care. Patients tend to present heterogeneous profiles of needs. However, there is no consensus in previous research about how patients' needs are organized. This study investigates both general and specific dimensions of patients' needs for care. METHODS: Patients' needs were assessed with ELADEB, an 18-domain self-report scale. The use of a self-assessment scale represents a unique way of obtaining patients' perceptions. A patient-centered psychiatric practice facilitates empowerment as it is based on the patients' personal motivations, needs, and wants. Four seventy-one patients' profiles were analyzed through exploratory factor analysis. RESULTS: A four-factor bifactor model, including one general factor and three specific factors of needs, was most adequate. Specific factors were (a) "finances" and "administrative tasks"; (b) "transports," "public places," "self-care," "housework," and "food"; and (c) "family," "children," "intimate relationships," and "friendship." CONCLUSION: As revealed by the general factor, patients expressing urgent needs in some domains are also more susceptible to report urgent needs in several other domains. This general factor relates to high versus low utilizers of public mental healthcare. Patients also present specific needs in life domains, which are organized in three dimensions: management, functional disabilities, and familial and interpersonal relationships. These dimensions relate to the different types of existing social support described in the literature.

Locating Intergenerational Sense of Self: Intersections of Genealogy with Leisure and Tourism

Situated at the intersection of leisure and tourism, there is currently a renewed interest and curiosity in ancestral lineages. Focusing on amateur genealogists who pursue, and travel for, a leisure engagement of genealogy, this qualitative research study endeavours to investigate their quests for personal identity and locations of an intergenerational sense of self. With the adoption of a narrative inquiry method, life story interviews were conducted with four amateur genealogists. Findings from an analysis of the narratives have been organized into five core themes, each of which contributes to our understanding of these amateur genealogists’ experiences of leisure and travel. While the amateur genealogists do not acknowledge their leisure engagements as a quest for personal identity, they make use of such engagements to locate an intergenerational sense of self and gain enriched self-understandings. Moreover, by facilitating intersections of genealogy, leisure, and tourism, several key insights are offered that may be of particular interest to scholars in both fields of study.

Organized Retail Market Boom and the Indian Society

IT and related services played a major role for India’s current 9.2. GDP growth. Organized retailing in India is one more example for its open economy. The IT industries where able develop a demand for Indian talents all over the world and improved their living standards. It directly impacts only a small minority of Indian population while organized retail affects every single Indian and every sector of Indian society. The paper gives a glimpse of the slow evolution of retail market over the years in India and its contribution for economic growth. The likely positive impact of this revolution in different sectors is enumerated. Paper addresses its ability to manipulate consumption pattern of society, increased customer satisfaction and likely change in the market shares of the different types of sellers. Paper discusses its flip sides like increasing social tension among families below poverty line and greater loss of self employment opportunities by this revolution. The main theme of enquiry of this paper is what it all means for the Indian society.

A direct comparison of one- and two-component dendritic self-assembled materials: elucidating molecular recognition pathways

This paper compares and contrasts, for the first time, one- and two-component gelation systems that are direct structural analogues and draws conclusions about the molecular recognition pathways that underpin fibrillar self-assembly. The new one-component systems comprise L-lysine-based dendritic headgroups covalently connected to an aliphatic diamine spacer chain via an amide bond, One-component gelators with different generations of headgroup (from first to third generation) and different length spacer chains are reported. The self-assembly of these dendrimers in toluene was elucidated using thermal measurements, circular dichroism (CD) and NMR spectroscopies, scanning electron microscopy (SEM), and small-angle X-ray scattering (SAXS). The observations are compared with previous results for the analogous two-component gelation system in which the dendritic headgroups are bound to the aliphatic spacer chain noncovalently via acid-amine interactions. The one-component system is inherently a more effective gelator, partly as a consequence of the additional covalent amide groups that provide a new hydrogen bonding molecular recognition pathway, whereas the two-component analogue relies solely on intermolecular hydrogen bond interactions between the chiral dendritic headgroups. Furthermore, because these amide groups are important in the assembly process for the one-component system, the chiral information preset in the dendritic headgroups is not always transcribed into the nanoscale assembly, whereas for the two-component system, fiber formation is always accompanied by chiral ordering because the molecular recognition pathway is completely dependent on hydrogen bond interactions between well-organized chiral dendritic headgroups.

Peptide mediated formation of hierarchically organized solution and solid state polymer nanostructures

Biologically-inspired peptide sequences have been explored as auxiliaries to mediate self-assembly of synthetic macromolecules into hierarchically organized solution and solid state nanostructures. Peptide sequences inspired by the coiled coil motif and "switch" peptides, which can adopt both amphiphilic alpha-helical and beta-strand conformations, were conjugated to poly(ethylene glycol) (PEG). The solution and solid state self-assembly of these materials was investigated using a variety of spectroscopic, scattering and microscopic techniques. These experiments revealed that the folding and organization properties of the peptide sequences are retained upon conjugation of PEG and that they provide the driving force for the formation of the different nanoscale structures which were observed. The possibility of using defined peptide sequences to direct structure formation of synthetic polymers together with the potential of peptide sequences to induce a specific biological response offers interesting prospects for the development of novel self-assembled and biologically active materials.

Dehydrodipeptide hydrogelators containing naproxen N‑Capped tryptophan: self-assembly, hydrogel characterization, and evaluation as potential drug nanocarriers

In this work, we introduce dipeptides containing tryptophan N-capped with the nonsteroidal anti-inflammatory drug naproxen and C-terminal dehydroamino acids, dehydrophenylalanine (ΔPhe), dehydroaminobutyric acid (ΔAbu), and dehydroalanine (ΔAla) as efficacious protease resistant hydrogelators. Optimized conditions for gel formation are reported. Transmission electron microscopy experiments revealed that the hydrogels consist of networks of micro/nanosized fibers formed by peptide self-assembly. Fluorescence and circular dichroism spectroscopy indicate that the self-assembly process is driven by stacking interactions of the aromatic groups. The naphthalene groups of the naproxen moieties are highly organized in the fibers through chiral stacking. Rheological experiments demonstrated that the most hydrophobic peptide (containing C-terminal ΔPhe) formed more elastic gels at lower critical gelation concentrations. This gel revealed irreversible breakup, while the C-terminal ΔAbu and ΔAla gels, although less elastic, exhibited structural recovery and partial healing of the elastic properties. A potential antitumor thieno[3,2-b]pyridine derivative was incorporated (noncovalently) into the gel formed by the hydrogelator containing C-terminal ΔPhe residue. Fluorescence and Förster resonance energy transfer measurements indicate that the drug is located in a hydrophobic environment, near/associated with the peptide fibers, establishing this type of hydrogel as a good drug-nanocarrier candidate.

Nanoscopic photoluminescence memory as a fingerprint of complexity in self-assembled alkyl/siloxane hybrids

A thermally activated photoluminescence memory effect, induced by a reversible order-disorder phase transition of the alkyl chains, is reported for highly organized bilayer alkyl/siloxane hybrids (see figure; left at room temperature, right at 120 degrees C). The emission energy is sensitive to the annihilation/formation of the hydrogen-bonded amide-amide array displaying a unique nanoscopic sensitivity (ca. 150 nm).

HEALTH EDUCATION IN THE CARE TO CLIENTS OF THE BLOOD GLUCOSE SELF-MONITORING PROGRAM

This article reports, in a systemized and analytical way, the experience of an Outreach Program in the period between 2010 and 2011. The study focused on health education interventions as strategies to improve the adherence of individuals with insulin- dependent diabetes mellitus (IDDM), clients of a blood glucose self-Monitoring program. In addition, we intended to contribute to the reorganization of the program's working processes in the unit. Health education strategies were used in both educational groups and home visits, thus permitting the provision of care that was more individualized. Data regarding the clients were organized on a spreadsheet and in files for the Family Health teams, which made it easier to identify the patients, including those who were absent, helping to decentralize the care. By using health education strategies, we intended to contribute to a more comprehensive and emancipatory care of the clients, aimed at a continuous reflection of the workers regarding their practices.

Self-similarities of periodic structures for a discrete model of a two-gene system

We report self-similar properties of periodic structures remarkably organized in the two-parameter space for a two-gene system, described by two-dimensional symmetric map. The map consists of difference equations derived from the chemical reactions for gene expression and regulation. We characterize the system by using Lyapunov exponents and isoperiodic diagrams identifying periodic windows, denominated Arnold tongues and shrimp-shaped structures. Period-adding sequences are observed for both periodic windows. We also identify Fibonacci-type series and Golden ratio for Arnold tongues, and period multiple-of-three windows for shrimps. (C) 2012 Elsevier B.V. All rights reserved.

Tetraurea derivatives of calix[4]arenes and oligocalix[4]arenes, synthesis and self-assembly = Tetraharnstoff-Derivate von Calix[4 ]arenen und Oligocalix[4]arenen, Synthese und Selbstorganisierung

Wide rim tetraurea calix[4]arenes form hydrogen bonded dimeric capsules in apolar solvents in the presence of a suitable guest, which must be included in the cavity. The monomeric and dimeric form are never observed simultaneously under usual conditions. In general the combination of two different alkyl or aryl tetraurea derivatives results in the mixture of two homodimers and a heterodimer, however, only the heterodimeric species is observed in the 1:1 mixture of aryl and tosyl ureas. The (hetero)dimerization of oligourea calix[4]arenes (units) was used to construct larger structures via self-assembly of multiple calixarenes (building blocks) containing two (or more) covalently connected units. Among these self-assembled structures linear or branched polymers, cyclic oligomers and well-organized dendrimers were envisaged. The synthesis of the building blocks requires the preparation of calix[4]arene units possessing one (or more) functional group at the narrow or wide rim. Finally the oligourea units were covalently connected either directly or via suitable spacers within appropriate building blocks using amide bonds. Self-assembly properties of such building blocks were investigated.

Supramolecular approaches to organized luminescent nanostructures for sensing, labeling and imaging applications

The common thread of this thesis is the will of investigating properties and behavior of assemblies. Groups of objects display peculiar properties, which can be very far from the simple sum of respective components’ properties. This is truer, the smaller is inter-objects distance, i.e. the higher is their density, and the smaller is the container size. “Confinement” is in fact a key concept in many topics explored and here reported. It can be conceived as a spatial limitation, that yet gives origin to unexpected processes and phenomena based on inter-objects communication. Such phenomena eventually result in “non-linear properties”, responsible for the low predictability of large assemblies. Chapter 1 provides two insights on surface chemistry, namely (i) on a supramolecular assembly based on orthogonal forces, and (ii) on selective and sensitive fluorescent sensing in thin polymeric film. In chapters 2 to 4 confinement of molecules plays a major role. Most of the work focuses on FRET within core-shell nanoparticles, investigated both through a simulation model and through experiments. Exciting results of great applicative interest are drawn, such as a method of tuning emission wavelength at constant excitation, and a way of overcoming self-quenching processes by setting up a competitive deactivation channel. We envisage applications of these materials as labels for multiplexing analysis, and in all fields of fluorescence imaging, where brightness coupled with biocompatibility and water solubility is required. Adducts of nanoparticles and molecular photoswitches are investigated in the context of superresolution techniques for fluorescence microscopy. In chapter 5 a method is proposed to prepare a library of functionalized Pluronic F127, which gives access to a twofold “smart” nanomaterial, namely both (i)luminescent and (ii)surface-functionalized SCSSNPs. Focus shifts in chapter 6 to confinement effects in an upper size scale. Moving from nanometers to micrometers, we investigate the interplay between microparticles flowing in microchannels where a constriction affects at very long ranges structure and dynamics of the colloidal paste.

Lipophilic nucleosides: studies toward self-assembled functional materials

Molecular self-assembly takes advantage of supramolecular non-covalent interactions (ionic, hydrophobic, van der Waals, hydrogen and coordination bonds) for the construction of organized and tunable systems. In this field, lipophilic guanosines can represent powerful building blocks thanks to their aggregation proprieties in organic solvents, which can be controlled by addition or removal of cations. For example, potassium ion can template the formation of piled G-quartets structures, while in its absence ribbon-like G aggregates are generated in solution. In this thesis we explored the possibility of using guanosines as scaffolds to direct the construction of ordered and self-assembled architectures, one of the main goals of bottom-up approach in nanotechnology. In Chapter III we will describe Langmuir-Blodgett films obtained from guanosines and other lipophilic nucleosides, revealing the “special” behavior of guanine in comparison with the other nucleobases. In Chapter IV we will report the synthesis of several thiophene-functionalized guanosines and the studies towards their possible use in organic electronics: the pre-programmed organization of terthiophene residues in ribbon aggregates could allow charge conduction through π-π stacked oligothiophene functionalities. The construction and the behavior of some simple electronic nanodevices based on these organized thiopehene-guanosine hybrids has been explored.

Self-Absorption and Luminescence Quantum Yields of Dye-Zeolite L Composites

Electronic absorption and fluorescence spectra based on transmission measurements of thin layers obtained from new perylene−zeolite L composites and new dye1,dye2−zeolite L sandwich composites, the latter acting as antenna systems, have been investigated and analyzed. The influence of extra- and intraparticle self-absorption on the spectral shape and fluorescence quantum yield is discussed in detail. Due to its intraparticle origin, self-absorption and re-emission can often not be avoided in organized systems such as dye−zeolite L composites where a high density of chromophores is a prerequisite for obtaining the desired photophysical properties. We show, however, that it can be avoided or at least minimized by preparing dye1,dye2−zeolite L sandwich composites where donors are present in a much larger amount than the acceptors because they act as antenna systems.

Self-Assessment in a Competency-Based Curriculum: Preliminary Findings

Introduction: The introduction of the ACGME core competency framework brought challenges of developing appropriate evaluation tools (i.e. self assessment) to provide evidence of competency. Baylor College of Medicine has 43 competency goals organized within the 6 ACGME domains, each domain having 4-10 goals. [See PDF for complete abstract]