Drug/Water interactions in hydrogel matrices

The primary aim of this research has been the investigation of the role of water structuring effects in the widely different extents of irritancy displayed by certain antibiotics. The compounds involved were members of the Lincomycin group of antibiotics. The aqueous solution behaviour of these co~pounds was studied using techniques such as vapour pressure osmometry end differential scanning calorimetry (D.S.C.). The effects of the antibiotics on water structure in hydrogel membrane preparations In which the equilibrium water content (E.W.C.) and constituent amounts of freezing and non-freezing water ware varied were also investigated using D.S.C. The permeability of water swollen hydrogel preparations to aqueous antibiotic solutions as well as other solutes were studied. A series of hydrogel preparations into which the antibiotics had been incorporated during polymerisation were developed and used in studies of the effects of the antibiotics end their water structure modifications on the permeation of a range of solutes.

Biological interactions with synthetic polymers

Anchorage dependent cell culture is a useful model for investigating the interface that becomes established when a synthetic polymer is placed in contact with a biological system. The primary aim of this interdisciplinary study was to systematically investigate a number of properties that were already considered to have an influence on cell behaviour and thereby establish the extent of their importance. It is envisaged that investigations such as these will not only further the understanding of the mechanisms that affect cell adhesion but may ultimately lead to the development of improved biomaterials. In this study, surface analysis of materials was carried out in parallel with culture studies using fibroblast cells. Polarity, in it's ability to undergo hydrogen bonding (eg with water and proteins), had an important affect on cell behaviour, although structural arrangement and crystallinity were not found to exert any marked influence. In addition, the extent of oxidation that had occurred during the process of manufacture of substrates was also important. The treatment of polystyrene with a selected series of acids and gas plasmas confirmed the importance of polarity, structural groups and surface charge and it was shown that this polymer was not unique among `hydrophobic' materials in it's inability to support cell adhesion. The individual water structuring groups within hydrogel polymers were also observed to have controlling effects on cell behaviour. An overall view of the biological response to both hydrogel and non-hydrogel materials highlighted the importance of surface oxidation, polarity, water structuring groups and surface charge. Initial steps were also taken to analyse foetal calf serum, which is widely used to supplement cell culture media. Using an array of analytical techniques, further experiments were carried out to observe any possible differences in the amounts of lipids and calcium that become deposited to tissue culture and bacteriological grade plastic under cell culture conditions.

Coherence and understanding in informal conversations between native and non-native speakers of English

This study investigates informal conversations between native English speakers and international students living and studying in the UK. 10 NNS participants recorded themselves during conversations with native speakers. The audio-recordings were transcribed and a fine-grained, qualitative analysis was employed to examine how the participants jointly achieved both coherence and understanding in the conversations, and more specifically how the NNSs contributed to this achievement. The key areas of investigation focused on features of topic management, such as topic initiations, changes and transitions, and on the impact which any communicative difficulties may have on the topical continuity of the conversations. The data suggested that these conversations flowed freely and coherently, and were marked by a relative scarcity of the communicative difficulties often associated with NS-NNS interactions. Moreover, language difficulties were found to have minimal impact on the topic development of the conversations. Unlike most previous research in the field, the data further indicated that the NNSs were able to make active contributions to the initiation and change of topics, and to employ a range of strategies to manage these effectively and coherently. The study considers the implications which the findings may have for teaching and learning, for second language acquisition research, and for non-native speakers everywhere.

Ontology-based protein-protein interactions extraction from literature using the hidden vector state model

This paper proposes a novel framework of incorporating protein-protein interactions (PPI) ontology knowledge into PPI extraction from biomedical literature in order to address the emerging challenges of deep natural language understanding. It is built upon the existing work on relation extraction using the Hidden Vector State (HVS) model. The HVS model belongs to the category of statistical learning methods. It can be trained directly from un-annotated data in a constrained way whilst at the same time being able to capture the underlying named entity relationships. However, it is difficult to incorporate background knowledge or non-local information into the HVS model. This paper proposes to represent the HVS model as a conditionally trained undirected graphical model in which non-local features derived from PPI ontology through inference would be easily incorporated. The seamless fusion of ontology inference with statistical learning produces a new paradigm to information extraction.

Topic continuity in informal conversations between native and non-native speakers of English

Topic management by non-native speakers (NNSs) during informal conversations has received comparatively little attention from researchers, and receives surprisingly little attention in second language learning and teaching. This article reports on one of the topic management strategies employed by international students during informal, social interactions with native-speaker peers, exploring the process of maintaining topic continuity following temporary suspensions of topics. The concept of side sequences is employed to illustrate the nature of different types of topic suspension, as well as the process of jointly negotiating a return to the topic. Extracts from the conversations show that such sequences were not exclusively occasioned by language difficulties, and that the non-native speaker participants were able to effect successful returns to the main topic of the conversations.

The N-terminus of CD14 acts to bind apoptotic cells and confers rapid-tethering capabilities on non-myeloid cells:CD14 and rapid tethering of apoptotic cells

Cell death and removal of cell corpses in a timely manner is a key event in both physiological and pathological situations including tissue homeostasis and the resolution of inflammation. Phagocytic clearance of cells dying by apoptosis is a complex sequential process comprising attraction, recognition, tethering, signalling and ultimately phagocytosis and degradation of cell corpses. A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within this process. The role of myeloid cell CD14 in mediating apoptotic cell interactions with macrophages has long been known though key molecules and residues involved have not been defined. Here we sought to further dissect the function of CD14 in apoptotic cell clearance. A novel panel of THP-1 cell-derived phagocytes was employed to demonstrate that CD14 mediates effective apoptotic cell interactions with macrophages in the absence of detectable TLR4 whilst binding and responsiveness to LPS requires TLR4. Using a targeted series of CD14 point mutants expressed in non-myeloid cells we reveal CD14 residue 11 as key in the binding of apoptotic cells whilst other residues are reported as key for LPS binding. Importantly we note that expression of CD14 in non-myeloid cells confers the ability to bind rapidly to apoptotic cells. Analysis of a panel of epithelial cells reveals that a number naturally express CD14 and that this is competent to mediate apoptotic cell clearance. Taken together these data suggest that CD14 relies on residue 11 for apoptotic cell tethering and it may be an important tethering molecule on so called 'non-professional' phagocytes thus contributing to apoptotic cell clearance in a non-myeloid setting. Furthermore these data establish CD14 as a rapid-acting tethering molecule, expressed in monocytes, which may thus confer responsiveness of circulating monocytes to apoptotic cell derived material. © 2013 Thomas et al.

Investigating the role of cholesterol in the formation of non-ionic surfactant based bilayer vesicles:thermal analysis and molecular dynamics

The aim of this research was to investigate the molecular interactions occurring in the formulation of non-ionic surfactant based vesicles composed monopalmitoyl glycerol (MPG), cholesterol (Chol) and dicetyl phosphate (DCP). In the formulation of these vesicles, the thermodynamic attributes and surfactant interactions based on molecular dynamics, Langmuir monolayer studies, differential scanning calorimetry (DSC), hot stage microscopy and thermogravimetric analysis (TGA) were investigated. Initially the melting points of the components individually, and combined at a 5:4:1 MPG:Chol:DCP weight ratio, were investigated; the results show that lower (90 C) than previously reported (120-140 C) temperatures could be adopted to produce molten surfactants for the production of niosomes. This was advantageous for surfactant stability; whilst TGA studies show that the individual components were stable to above 200 C, the 5:4:1 MPG:Chol:DCP mixture show ∼2% surfactant degradation at 140 C, compared to 0.01% was measured at 90 C. Niosomes formed at this lower temperature offered comparable characteristics to vesicles prepared using higher temperatures commonly reported in literature. In the formation of niosome vesicles, cholesterol also played a key role. Langmuir monolayer studies demonstrated that intercalation of cholesterol in the monolayer did not occur in the MPG:Chol:DCP (5:4:1 weight ratio) mixture. This suggests cholesterol may support bilayer assembly, with molecular simulation studies also demonstrating that vesicles cannot be built without the addition of cholesterol, with higher concentrations of cholesterol (5:4:1 vs 5:2:1, MPG:Chol:DCP) decreasing the time required for niosome assembly. © 2013 Elsevier B.V.

Emotion recognition and alexithymia in females with non-clinical disordered eating

Objectives: The aims were to determine if emotion recognition deficits observed in eating disorders generalise to non-clinical disordered eating and to establish if other psychopathological and personality factors contributed to, or accounted for, these deficits. Design: Females with high (n=23) and low (n=22) scores on the Eating Disorder Inventory (EDI) were assessed on their ability to recognise emotion from videotaped social interactions. Participants also completed a face memory task, a Stroop task, and self-report measures of alexithymia, depression and anxiety. Results: Relative to the low EDI group, high EDI participants exhibited a general deficit in recognition of emotion, which was related to their scores on the alexithymia measure and the bulimia subscale of the EDI. They also exhibited a specific deficit in the recognition of anger, which was related to their scores on the body dissatisfaction subscale of the EDI. Conclusions: In line with clinical eating disorders, non-clinical disordered eating is associated with emotion recognition deficits. However, the nature of these deficits appears to be dependent upon the type of eating psychopathology and the degree of co-morbid alexithymia.

Real-time detection of DNA interactions with long-period fiber-grating-based biosensor

Using an optical biosensor based on a dual-peak long-period fiber grating, we have demonstrated the detection of interactions between biomolecules in real time. Silanization of the grating surface was successfully realized for the covalent immobilization of probe DNA, which was subsequently hybridized with the complementary target DNA sequence. It is interesting to note that the DNA biosensor was reusable after being stripped off the hybridized target DNA from the grating surface, demonstrating a function of multiple usability. © 2007 Optical Society of America.

Polymer-lipid interactions:biomimetic self-assembly behaviour and surface properties of poly(styrene-alt-maleic acid) with diacylphosphatidylcholines

Abstract Various lubricating body fluids at tissue interfaces are composed mainly of combinations of phospholipids and amphipathic apoproteins. The challenge in producing synthetic replacements for them is not replacing the phospholipid, which is readily available in synthetic form, but replacing the apoprotein component, more specifically, its unique biophysical properties rather than its chemistry. The potential of amphiphilic reactive hypercoiling behaviour of poly(styrene-alt-maleic acid) (PSMA) was studied in combination with two diacylphosphatidylcholines (PC) of different chain lengths in aqueous solution. The surface properties of the mixtures were characterized by conventional Langmuir-Wilhelmy balance (surface pressure under compression) and the du Noüy tensiometer (surface tension of the non-compressed mixtures). Surface tension values and 31P NMR demonstrated that self-assembly of polymer-phospholipid mixtures were pH and concentration-dependent. Finally, the particle size and zeta potential measurements of this self-assembly showed that it can form negatively charged nanosized structures that might find use as drug or lipids release systems on interfaces such as the tear film or lung interfacial layers. The structural reorganization was sensitive to the alkyl chain length of the PC.

Computational modeling of biodegradable starch based polymer composites

Purpose. The goal of this study is to improve the favorable molecular interactions between starch and PPC by addition of grafting monomers MA and ROM as compatibilizers, which would advance the mechanical properties of starch/PPC composites. ^ Methodology. DFT and semi-empirical methods based calculations were performed on three systems: (a) starch/PPC, (b) starch/PPC-MA, and (c) starch-ROM/PPC. Theoretical computations involved the determination of optimal geometries, binding-energies and vibrational frequencies of the blended polymers. ^ Findings. Calculations performed on five starch/PPC composites revealed hydrogen bond formation as the driving force behind stable composite formation, also confirmed by the negative relative energies of the composites indicating the existence of binding forces between the constituent co-polymers. The interaction between starch and PPC is also confirmed by the computed decrease in stretching CO and OH group frequencies participating in hydrogen bond formation, which agree qualitatively with the experimental values. ^ A three-step mechanism of grafting MA on PPC was proposed to improve the compatibility of PPC with starch. Nine types of 'blends' produced by covalent bond formation between starch and MA-grafted PPC were found to be energetically stable, with blends involving MA grafted at the 'B' and 'C' positions of PPC indicating a binding-energy increase of 6.8 and 6.2 kcal/mol, respectively, as compared to the non-grafted starch/PPC composites. A similar increase in binding-energies was also observed for three types of 'composites' formed by hydrogen bond formation between starch and MA-grafted PPC. ^ Next, grafting of ROM on starch and subsequent blend formation with PPC was studied. All four types of blends formed by the reaction of ROM-grafted starch with PPC were found to be more energetically stable as compared to the starch/PPC composite and starch/PPC-MA composites and blends. A blend of PPC and ROM grafted at the ' a&d12; ' position on amylose exhibited a maximal increase of 17.1 kcal/mol as compared with the starch/PPC-MA blend. ^ Conclusions. ROM was found to be a more effective compatibilizer in improving the favorable interactions between starch and PPC as compared to MA. The ' a&d12; ' position was found to be the most favorable attachment point of ROM to amylose for stable blend formation with PPC.^

The relationship between classroom interactions and exclusionary discipline as a social practice: A critical microethnograhy

Exclusionary school discipline results in students being removed from classrooms as a consequence of their disruptive behavior and may lead to subsequent suspension and/or expulsion. Literature documents that nondominant students, particularly Black males, are disproportionately impacted by exclusionary discipline, to the point that researchers from a variety of critical perspectives consider exclusionary school discipline an oppressive educational practice and condition. Little or no research examines specific teacher-student social interactions within classrooms that influence teachers’ decisions to use or not use exclusionary discipline. Therefore, this study set forth the central research question: In relation to classroom interactions in alternative education settings, what accounts for teachers’ use or non-use of exclusionary discipline with students? A critical social practice theory of learning served as the framework for exploring this question, and a critical microethnographic methodology informed the data collection and analysis. ^ Criterion sampling was used to select four classrooms in the same alternative education school with two teachers who frequently and two who rarely used exclusionary discipline. Nine stages of data collection and reconstructive data analysis were conducted. Data collection involved video recorded classroom observations, digitally recorded interviews of teachers and students discussing selected video segments, and individual teacher interviews. Reconstructive data analysis procedures involved hermeneutic inferencing of possible underlying meanings, critical discourse analysis, interactive power analysis and role analysis, thematic analysis of the interactions in each classroom, and a final comparative analysis of the four classrooms. ^ Four predominant themes of social interaction (resistance, conformism, accommodation, and negotiation) emerged with terminology adapted from Giroux’s (2001) theory of resistance in education and Third Space theory (Gutiérrez, 2008). Four types of power (normative, coercive, interactively established contracts, and charm), based on Carspecken’s (1996) typology, were found in the interactions between teacher and students in varying degrees for different purposes. ^ This research contributes to the knowledge base on teacher-student classroom interactions, specifically in relation to exclusionary discipline. Understanding how the themes and varying power relations influence their decisions and actions may enable teachers to reduce use of exclusionary discipline and remain focused on positive teacher-student academic interactions. ^

Interactions between endothelin receptor B and transcription factors Sox10 and Pax3 in the melanocyte lineage

Genetic interactions that underlie developmental processes such as cell differentiation and pattern formation are complex and difficult to elucidate. Neural Crest (NC) cells and their derivatives offer an optimal system in which to probe for these complex interactions as they acquire different cell fates and constitute a variety of structures. The transcription factors Sox10 and Pax3 as well as the transmembrane receptor Endothelin receptor b (Ednrb) are temporally and spatially co-expressed early in NC cells and mutations in these genes lead to similar hypopigmentation phenotypes due to a reduced number of NC-derived melanocyte precursors, the melanoblasts. The goal of this study was to establish whether Sox10 and Ednrb or Pax3 and Ednrb interact to promote normal murine melanocyte development. Crosses of Sox10 or Pax3 with Ednrb heterozygous mutants showed that the double heterozygous hypopigmentation phenotype was significantly more pronounced than phenotypes of single heterozygotes, implying that a synergistic interaction exists between Sox10 and Ednrb and Pax3 and Ednrb. This interaction was further explored by the attempt to rescue the Sox10 and Pax3 hypopigmentation phenotypes by the transgenic addition of Ednrb to melanoblasts. Pigmentation was completely restored in the Sox10 and partially restored in the Pax3 mutant mice. The comparison of the number of melanoblasts in transgenic and non-transgenic Sox10 mutant embryos showed that the transgenic rescue occurred as early as E11.5, a critical time for melanoblast population expansion. Cell survival assays indicated that the rescue was not due to an effect of the transgene on melanoblast survival. A novel phenotype arose when studying the interaction between Ednrb and Pax3. Newborns appeared normal but by 3.5 weeks of age, the affected pups were smaller than normal littermates and developed a dome-shaped head; some also developed thoracic kyphosis. Affected pups were dead by 4 weeks of age: 80% were Pax3Sp/+ and 75% were female. When compared to normal littermates, affected mice had brains with enlarged 4th ventricles and more glia while skeletal staining showed kyphosis, wider rib cages and pelvic differences. An epistatic interaction resulting from the mixing of genetic backgrounds that is exacerbated in the presence of Pax3 heterozygosity is suspected.

Multiple predator effects and native prey responses to two non-native Everglades cichlids

Non-native predators may have negative impacts on native communities, and these effects may be dependent on interactions among multiple non-native predators. Sequential invasions by predators can enhance risk for native prey. Prey have a limited ability to respond to multiple threats since appropriate responses may conflict, and interactions with recent invaders may be novel. We examined predator–prey interactions among two non-native predators, a recent invader, the African jewelfish, and the longer-established Mayan cichlid, and a native Florida Everglades prey assemblage. Using field enclosures and laboratory aquaria, we compared predatory effects and antipredator responses across five prey taxa. Total predation rates were higher for Mayan cichlids, which also targeted more prey types. The cichlid invaders had similar microhabitat use, but varied in foraging styles, with African jewelfish being more active. The three prey species that experienced predation were those that overlapped in habitat use with predators. Flagfish were consumed by both predators, while riverine grass shrimp and bluefin killifish were eaten only by Mayan cichlids. In mixed predator treatments, we saw no evidence of emergent effects, since interactions between the two cichlid predators were low. Prey responded to predator threats by altering activity but not vertical distribution. Results suggest that prey vulnerability is affected by activity and habitat domain overlap with predators and may be lower to newly invading predators, perhaps due to novelty in the interaction.

Law Enforcement Actions in Urban Spaces Governed by Violent Non-State Entities: Lessons from Latin America

In response to a crime epidemic afflicting Latin America since the early 1990s, several countries in the region have resorted to using heavy-force police or military units to physically retake territories de facto controlled by non-State criminal or insurgent groups. After a period of territory control, the heavy forces hand law enforcement functions in the retaken territories to regular police officers, with the hope that the territories and their populations will remain under the control of the state. To a varying degree, intensity, and consistency, Brazil, Colombia, Mexico, and Jamaica have adopted such policies since the mid-1990s. During such operations, governments need to pursue two interrelated objectives: to better establish the state’s physical presence and to realign the allegiance of the population in those areas toward the state and away from the non-State criminal entities. From the perspective of law enforcement, such operations entail several critical decisions and junctions, such as: Whether or not to announce the force insertion in advance. The decision trades off the element of surprise and the ability to capture key leaders of the criminal organizations against the ability to minimize civilian casualties and force levels. The latter, however, may allow criminals to go to ground and escape capture. Governments thus must decide whether they merely seek to displace criminal groups to other areas or maximize their decapitation capacity. Intelligence flows rarely come from the population. Often, rival criminal groups are the best source of intelligence. However, cooperation between the State and such groups that goes beyond using vetted intelligence provided by the groups, such as a State tolerance for militias, compromises the rule-of-law integrity of the State and ultimately can eviscerate even public safety gains. Sustaining security after initial clearing operations is at times even more challenging than conducting the initial operations. Although unlike the heavy forces, traditional police forces, especially if designed as community police, have the capacity to develop trust of the community and ultimately focus on crime prevention, developing such trust often takes a long time. To develop the community’s trust, regular police forces need to conduct frequent on-foot patrols with intensive nonthreatening interactions with the population and minimize the use of force. Moreover, sufficiently robust patrol units need to be placed in designated beats for substantial amount of time, often at least over a year. Establishing oversight mechanisms, including joint police-citizens’ boards, further facilities building trust in the police among the community. After disruption of the established criminal order, street crime often significantly rises and both the heavy-force and community-police units often struggle to contain it. The increase in street crime alienates the population of the retaken territory from the State. Thus developing a capacity to address street crime is critical. Moreover, the community police units tend to be vulnerable (especially initially) to efforts by displaced criminals to reoccupy the cleared territories. Losing a cleared territory back to criminal groups is extremely costly in terms of losing any established trust and being able to recover it. Rather than operating on a priori determined handover schedule, a careful assessment of the relative strength of regular police and criminal groups post-clearing operations is likely to be a better guide for timing the handover from heavy forces to regular police units. Cleared territories often experience not only a peace dividend, but also a peace deficit – in the rise new serious crime (in addition to street crime). Newly – valuable land and other previously-inaccessible resources can lead to land speculation and forced displacement; various other forms of new crime can also significantly rise. Community police forces often struggle to cope with such crime, especially as it is frequently linked to legal business. Such new crime often receives little to no attention in the design of the operations to retake territories from criminal groups. But without developing an effective response to such new crime, the public safety gains of the clearing operations can be altogether lost.