Paralytic shellfish poisoning (PSP) toxin binders for optical biosensor technology: problems and possibilities for the future: a review

This review examines the developments in optical biosensor technology, which uses the phenomenon of surface plasmon resonance, for the detection of paralytic shellfish poisoning (PSP) toxins. Optical biosensor technology measures the competitive biomolecular interaction of a specific biological recognition element or binder with a target toxin immobilised onto a sensor chip surface against toxin in a sample. Different binders such as receptors and antibodies previously employed in functional and immunological assays have been assessed. Highlighted are the difficulties in detecting this range of low molecular weight toxins, with analogues differing at four chemical substitution sites, using a single binder. The complications that arise with the toxicity factors of each toxin relative to the parent compound, saxitoxin, for the measurement of total toxicity relative to the mouse bioassay are also considered. For antibodies, the cross-reactivity profile does not always correlate to toxic potency, but rather to the toxin structure to which it was produced. Restrictions and availability of the toxins makes alternative chemical strategies for the synthesis of protein conjugate derivatives for antibody production a difficult task. However, when two antibodies with different cross-reactivity profiles are employed, with a toxin chip surface generic to both antibodies, it was demonstrated that the cross-reactivity profile of each could be combined into a single-assay format. Difficulties with receptors for optical biosensor analysis of low molecular weight compounds are discussed, as are the potential of alternative non-antibody-based binders for future assay development in this area.

Possibilities for change? Diversity in Post-Conflict Belfast

Belfast is often presented as an exemplary divided or post-conflict city. However, this focus can be limiting and an exploration of alternative narratives for Belfast is needed. This paper investigates the diversification of post-conflict Belfast in light of the substantial migration which has occurred in the last decade, outlining the complexities of an emerging narrative of diversity. We note discrepancies in how racial equality is dealt with at an institutional level and report on the unevenness of migrant geographies, issues which require future consideration. We also raise questions that problematize the easy assumption that cultural diversity ameliorates existing sectarian divisions.

Recent Developments in the Law of Torts in Northern Ireland Annual Conference of the Irish Association of Law Teachers

This paper reviews decisions from the Northern Ireland and England and Wales High Courts and Courts of Appeal as well as the UK Supreme Court relating to tort and principally to the tort of negligence in the past 12 months or so.

In structure, the paper will be presented in four parts. First, three preliminary points relating to contemporary features of the NI civil courts: personal litigants – Devine v McAteer [2012] NICA 30 (7 September 2012); pre-action protocols – Monaghan v Graham [2013] NIQB 53 (3 May 2013); and the rise of alternative dispute resolution. On the last named issue, the recent decision of PGF II SA v OMFS Company 1 Ltd [2013] EWCA Civ 1288 (23 October 2013) on unreasonable refusal to mediate, will be discussed.

Second, the paper moves to consider the law of negligence generally and case law from the NI High Court reiterating Lord Hoffmann’s view in Tomlinson v Congleton Borough Council [2004] 1 AC 46 that no duty of care arises from obvious risks of injury. In this, reference will be made to the application of the above “Hoffmann principle” in West Sussex County Council v Pierce [2013] EWCA Civ 1230 (16 October 2013), which concerned an accident sustained by a child at school. A similar set of facts was presented recently to the UK Supreme Court in Woodland v Essex County Council [2013] UKSC 66 (23 October 2013). The decision there, on non-delegable duties of care, will have a significant impact for schools in the provision of extracurricular activities.

Third, I will review a NI case of note on the duty of care of solicitors in the context of professional negligence in the context of conflicting advice by counsel.

Fourth, I will examine a series of cases on employer liability and including issues such as the duty of care towards the volunteer worker; tort and safety at work principles generally; and, more specifically, the duty of care of the employer towards an employee who suffers psychiatric illness as a result of stress and/or harassment at work. On the issue of workplace stress, the NI courts have made extensive reference to the Hale LJ principles found in the Court of Appeal decision of Hatton v Sutherland [2002] 1 All ER 1 and applied to those who have suffered trauma in reporting on or policing “the troubles” in Northern Ireland. On the issue of statutory harassment at work, the paper will also mention the UK Supreme Court’s decision in Hayes v Willoughby [2013] UKSC 17 (20 March 2013).

The Experience and Practice of Approved Social Workers in Northern Ireland

This article reports on the first extensive survey of Approved Social Worker (ASW) activity under the Mental Health (Northern Ireland) Order 1986. The integrated health and social services organizational structure, the adverse effects on individual mental health of the legacy of thirty years of civil conflict and the move from hospital to community care are significant features which have influenced the delivery of mental health social work services locally. The practice and experience of ASWs was surveyed by postal questionnaire and user and carer experience of compulsory hospital admission was investigated by a series of focus groups. The study revealed that two‐thirds of ASWs had experience of acting as an applicant in compulsory hospital admission during the past two years. Nearly half (42 per cent) of these ASWs had reported experience of between one and five admissions and one‐tenth had completed over twenty admissions in the two‐year period. In only a small minority of cases did joint face‐to‐face assessment with the General Practitioner (doctor) take place; nearly half of ASWs reported difficulties in obtaining transport; and only one‐fifth of ASWs had experience of acting as a second approved social worker. Half of ASWs reported experience of guardianship, either as applicant or in making the recommendation. Both service users and carers reported a lack of understanding about the role of the ASW and complained about the lack of alternative resources that ASWs could use to prevent hospital admissions. These findings are discussed and a number of recommendations are proposed for improvements to approved social worker practice.

Pilot-scale evaluation of the application of low pH-inducible polyphosphate accumulation to the biological removal of phosphate from wastewaters.

To investigate the possible biotechnological application of the phenomenon of low pH-inducible phosphate uptake and polyphosphate accumulation, previously reported using pure microbial cultures and under laboratory conditions, a 2000 L activated sludge pilot plant was constructed at a municipal sewage treatment works. When operated as a single-stage reactor this removed more than 60% of influent phosphate from primary settled sewage at a pH of 6.0, as opposed to approximately 30% at the typical operational pH for the works of 7.0-7.3-yet without any deleterious effect on other treatment parameters. At these pH values the phosphorus content of the sludge was, respectively, 4.2% and 2.0%. At pH 6.0 some 33.9% of sludge microbial cells were observed to contain polyphosphate inclusions; the corresponding value at pH 7.0 was 18.7%. Such a process may serve as a prototype for the development of alternative biological and chemical options for phosphate removal from wastewaters.

The Equalization of Effective Communicative Freedom: Democratic Justice in the Constitutional State and Beyond

Jurgen Habermas takes the realization of rights through the democratic self-organization of legal communities to be the normative core of emancipatory politics. In this article I explore the implications of this claim in relation to the requirements of justice. I argue that Habermas's discourse theory of democratic legitimacy presupposes a substantive principle of justice that demands the equalization of effective communicative freedom for all structurally constituted social groups in any constitutional state. This involves the elimination of a range of structural injustices rooted in the complex interrelationships between political, economic and cultural orders. In the final section I sketch briefly the implications of this analysis in the context of ongoing globalization processes. It is suggested that the most effective way to establish a just system of global governance is to equalize effective communicative freedom among nation-states.

Analyzing the degree of conflict among belief functions.

The study of alternative combination rules in DS theory when evidence is in conflict has emerged again recently as an interesting topic, especially in data/information fusion applications. These studies have mainly focused on investigating which alternative would be appropriate for which conflicting situation, under the assumption that a conflict is identified. The issue of detection (or identification) of conflict among evidence has been ignored. In this paper, we formally define when two basic belief assignments are in conflict. This definition deploys quantitative measures of both the mass of the combined belief assigned to the emptyset before normalization and the distance between betting commitments of beliefs.We argue that only when both measures are high, it is safe to say the evidence is in conflict. This definition can be served as a prerequisite for selecting appropriate combination rules.

Entanglement of mixed macroscopic superpositions: An entangling-power study

We investigate entanglement properties of a recently introduced class of macroscopic quantum superpositions in two-mode mixed states. One of the tools we use in order to infer the entanglement in this non-Gaussian class of states is the power to entangle a qubit system. Our study reveals features which are hidden in a standard approach to entanglement investigation based on the uncertainty principle of the quadrature variables. We briefly describe the experimental setup corresponding to our theoretical scenario and a suitable modification of the protocol which makes our proposal realizable within the current experimental capabilities.

Boundary conditions in the simplest model of linear and second harmonic magneto-optical effects

This paper is concerned with linear and nonlinear magneto- optical effects in multilayered magnetic systems when treated by the simplest phenomenological model that allows their response to be represented in terms of electric polarization, The problem is addressed by formulating a set of boundary conditions at infinitely thin interfaces, taking into account the existence of surface polarizations. Essential details are given that describe how the formalism of distributions (generalized functions) allows these conditions to be derived directly from the differential form of Maxwell's equations. Using the same formalism we show the origin of alternative boundary conditions that exist in the literature. The boundary value problem for the wave equation is formulated, with an emphasis on the analysis of second harmonic magneto-optical effects in ferromagnetically ordered multilayers. An associated problem of conventions in setting up relationships between the nonlinear surface polarization and the fundamental electric field at the interfaces separating anisotropic layers through surface susceptibility tensors is discussed. A problem of self- consistency of the model is highlighted, relating to the existence of resealing procedures connecting the different conventions. The linear approximation with respect to magnetization is pursued, allowing rotational anisotropy of magneto-optical effects to be easily analyzed owing to the invariance of the corresponding polar and axial tensors under ordinary point groups. Required representations of the tensors are given for the groups infinitym, 4mm, mm2, and 3m, With regard to centrosymmetric multilayers, nonlinear volume polarization is also considered. A concise expression is given for its magnetic part, governed by an axial fifth-rank susceptibility tensor being invariant under the Curie group infinityinfinitym.

Reactivity of the 4d transition metals toward N hydrogenation and NH dissociation: A DFT-based HSAB analysis

The density functional theory (DFT) based hard-soft acid-base (HSAB) reactivity indices, including the electrophilicity index, have been successfully applied to many areas of molecular chemistry. In this work we test the applicability of such an approach to fundamental surface chemistry. We have considered, as prototypical surface reactions, both the hydrogenation of atomic nitrogen and the dissociative adsorption of the NH molecular radical. By use of a DFT methodology, the minimum energy reaction pathways, and corresponding reaction barriers, of the above reactions over Zr(001), Nb(110), Mo(110), Tc(001), Ru(001), Rh(111), and Pd(111) have been determined. By consideration of the chemical potential and chemical hardness of the surface metal atoms, and the principle of electronegativity equalization, it is found that the charge transferred to the NH radical during the process of dissociative adsorption correlates very well with that determined by Mulliken population analysis. Furthermore, it is found that the stability of the NH/surface transition state complex relates directly to this charge transfer and that the trend in transition state stability predicted by a HSAB; treatment correlates very strongly with that determined by DFT calculations. With regards to N hydrogenation, we find that during the course of the reaction, H loses cohesion to the surface, as it must migrate from a 3-fold hollow site to either a bridge or top site, to react with N. Partial density of states (PDOS) and Mulliken population analysis reveal that this loss of bonding is accompanied by charge transfer from H to the surface metal atoms. Moreover, by simple modeling, we show that the reaction barriers are directly proportional to this mandatory charge transfer. Indeed, it is found that the reaction barriers correlate very well with the electrophilicity index of the metal atoms.

Phase I Study Of The Poly(ADP-Ribose) Polymerase Inhibitor, AG014699, In Combination With Temozolomide in Patients with Advanced Solid Tumors

Purpose: One mechanism of tumor resistance to cytotoxic therapy is repair of damaged DNA. Poly(ADP-ribose) polymerase (PARP)-1 is a nuclear enzyme involved in base excision repair, one of the five major repair pathways. PARP inhibitors are emerging as a new class of agents that can potentiate chemotherapy and radiotherapy. The article reports safety, efficacy, pharmacokinetic, and pharmacodynamic results of the first-in-class trial of a PARP inhibitor, AG014699, combined with temozolomide in adults with advanced malignancy.

Experimental Design: Initially, patients with solid tumors received escalating doses of AG014699 with 100 mg/m2/d temozolomide × 5 every 28 days to establish the PARP inhibitory dose (PID). Subsequently, AG014699 dose was fixed at PID and temozolomide escalated to maximum tolerated dose or 200 mg/m2 in metastatic melanoma patients whose tumors were biopsied. AG014699 and temozolomide pharmacokinetics, PARP activity, DNA strand single-strand breaks, response, and toxicity were evaluated.

Results: Thirty-three patients were enrolled. PARP inhibition was seen at all doses; PID was 12 mg/m2 based on 74% to 97% inhibition of peripheral blood lymphocyte PARP activity. Recommended doses were 12 mg/m2 AG014699 and 200 mg/m2 temozolomide. Mean tumor PARP inhibition at 5 h was 92% (range, 46-97%). No toxicity attributable to AG014699 alone was observed. AG014699 showed linear pharmacokinetics with no interaction with temozolomide. All patients treated at PID showed increases in DNA single-strand breaks and encouraging evidence of activity was seen.

Conclusions: The combination of AG014699 and temozolomide is well tolerated, pharmacodynamic assessments showing proof of principle of the mode of action of this new class of agents.

Heat capacities of ionic liquids as a function of temperature at 0.1 MPa. measurement and prediction

Heat capacities of nine ionic liquids were measured from (293 to 358) K by using a heat flux differential scanning calorimeter. The impact of impurities (water and chloride content) in the ionic liquid was analyzed to estimate the overall uncertainty. The Joback method for predicting ideal gas heat capacities has been extended to ionic liquids by the generation of contribution parameters for three new groups. The principle of corresponding states has been employed to enable the subsequent calculation of liquid heat capacities for ionic liquids, based on critical properties predicted using the modified Lydersen-Joback-Reid method, as a function of the temperature from (256 to 470) K. A relative absolute deviation of 2.9% was observed when testing the model against 961 data points from 53 different ionic liquids reported previously and measured within this study.

The Challenges of Universalising Religions: the Kabbalah Centre in France and Britain.

The Kabbalah Centre is an offshoot of Judaism which since the 1990s has spread kabbalistic teaching in several countries to a religiously diverse audience. This article compares two European branches of the Kabbalah Centre: the flourishing London Centre, and the Parisian Centre that declined in the late 1990s before closing its doors in 2005. It emphasizes in particular the responses they stirred from the media, anticult movements, Orthodox Judaism and the Jewish population. Ultimately, this case study allows us to observe, in situ, the trajectory of a global religion, torn between its Jewish roots and universalistic ambitions. It emphasizes the importance, in this process, of the relationship it maintains, willingly or not, with its original religious frame. Consequently, the importance of local contexts is raised, illustrating the impact and combination of diverse factors. In addition to public and official responses to religious diversity, religious movements are affected by the religious landscape and the structures and authorities of religious organizations, as well as the religious and cultural characteristics of the population. Ultimately, this article underscores the complexity of the globalization of religion, which embraces a wide range of complex, sometimes ambiguous, situations lying between strong particularistic identity-claims and cosmopolitan, universalistic ambitions.