Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid

Background: The work in this study appraised photodynamic treatment (PDT) as a treatment method for vulval intraepithelial neoplasia (VIN) using a novel bioadhesive patch to deliver aminolevulinic acid. An analysis of changes in expression of apoptotic and cell cycle proteins (p53, p21, Mdm2, Blc-2, Bax, Ki-67) in response to PDT was evaluated. Methods: PDT was performed using non-laser light, either as a one or two-cycle treatment, with clinical and pathological assessment following after 6 weeks. Twenty-three patients with 25 VIN lesions underwent 49 cycles of PDT Patches were designed to conform to uneven vulval skin and contained 38 mg cm(-2) aminolevulinic acid. Assessment was carried out at 6 weeks post-treatment. Patient-based treatment assessment, along with clinical and pathological changes, were monitored. Immunohistochemical staining was used to elucidate a possible biomolecular basis for induced cellular changes. Results: Most patients (52%) reported a symptomatic response, with normal pathology restored in 38% of lesions. The patch was easy to apply and remove, causing minimal discomfort. Fluorescence inspection confirmed protoporphyrin accumulation. Pain during implementation of PDT was problematic, necessitating some form of local analgesia. Changes in expression of cell cycle and apoptotic-related proteins suggested involvement of apoptotic pathways. Down regulation of p21 and inverse changes in Bcl-2 and Bax were key findings. Conclusion: Treatment of VIN lesions using a novel bioadhesive patch induced changes in cell cycle and apoptotic proteins in response to PDT with possible utilisation of apoptotic pathways. The efficacy of PDT in treating VIN could be improved by a better understanding of these apoptotic mechanisms, the influence of factors, such as HPV status, and of the need for effective pain management.

Novel bioadhesive patch-type system for photodynamic vulvodynia therapy after delivery of 5-aminolevulinic acid - Preliminary evaluation

OBJECTIVE: To assess the applicability of photodynamic therapy (PDT) in the management of vulvodynia whereby a novel, patch-type system, loaded with 5-aminolevulinic acid (ALA), was used to administer PDT to vulvar regions displaying the characteristics of vulvodynia.

A type system for value-dependent information flow analysis

Information systems are widespread and used by anyone with computing devices as well as corporations and governments. It is often the case that security leaks are introduced during the development of an application. Reasons for these security bugs are multiple but among them one can easily identify that it is very hard to define and enforce relevant security policies in modern software. This is because modern applications often rely on container sharing and multi-tenancy where, for instance, data can be stored in the same physical space but is logically mapped into different security compartments or data structures. In turn, these security compartments, to which data is classified into in security policies, can also be dynamic and depend on runtime data. In this thesis we introduce and develop the novel notion of dependent information flow types, and focus on the problem of ensuring data confidentiality in data-centric software. Dependent information flow types fit within the standard framework of dependent type theory, but, unlike usual dependent types, crucially allow the security level of a type, rather than just the structural data type itself, to depend on runtime values. Our dependent function and dependent sum information flow types provide a direct, natural and elegant way to express and enforce fine grained security policies on programs. Namely programs that manipulate structured data types in which the security level of a structure field may depend on values dynamically stored in other fields The main contribution of this work is an efficient analysis that allows programmers to verify, during the development phase, whether programs have information leaks, that is, it verifies whether programs protect the confidentiality of the information they manipulate. As such, we also implemented a prototype typechecker that can be found at http://ctp.di.fct.unl.pt/DIFTprototype/.

BOUSSINESQ-TYPE SYSTEM OF EQUATIONS IN THE BENARD-MARANGONI SYSTEM

A system of coupled evolution equations for the bulk velocity and the surface displacement is found to govern the long-wavelength perturbations in a Benard-Marangoni system. This system of equations, involving nonlinearity, dispersion, and dissipation, is a generalization of the usual Boussinesq system.

A type system with usage aspects

Linear typing schemes can be used to guarantee non-interference and so the soundness of in-place update with respect to a functional semantics. But linear schemes are restrictive in practice, and more restrictive than necessary to guarantee soundness of in-place update. This limitation has prompted research into static analysis and more sophisticated typing disciplines to determine when in-place update may be safely used, or to combine linear and non-linear schemes. Here we contribute to this direction by defining a new typing scheme that better approximates the semantic property of soundness of in-place update for a functional semantics. We begin from the observation that some data are used only in a read-only context, after which it may be safely re-used before being destroyed. Formalising the in-place update interpretation in a machine model semantics allows us to refine this observation, motivating three usage aspects apparent from the semantics that are used to annotate function argument types. The aspects are (1) used destructively, (2), used read-only but shared with result, and (3) used read-only and not shared with the result. The main novelty is aspect (2), which allows a linear value to be safely read and even aliased with a result of a function without being consumed. This novelty makes our type system more expressive than previous systems for functional languages in the literature. The system remains simple and intuitive, but it enjoys a strong soundness property whose proof is non-trivial. Moreover, our analysis features principal types and feasible type reconstruction, as shown in M. Konen'y (In TYPES 2002 workshop, Nijmegen, Proceedings, Springer-Verlag, 2003).

Application of a PERT-Type System and "Crashing" in a Food Service Operation

A pert-type system, a combination of the program evaluation and review technique (PERT) and the critical path method (CPM), might be used by the hospitality industry to improve planning and control of complex functions. The author discusses this management science technique and how it can assist.

Observation of coherent population trapping in a V-type two-electron system

We observe coherent population trapping (CPT) in a two-electron atom-Yb-174-using the S-1(0), F= 0 -> P-3(1), F `= 1 transition. CPT is not possible for such a transition according to one-electron theory because the magnetic sublevels form a V-type system, but in a two-electron atom like Yb, the interaction of the electrons transforms the level structure into a V-type system, which allows the formation of a dark state and hence the observation of CPT. Since the two levels involved are degenerate, we use a magnetic field to lift the degeneracy. The single fluorescence dip then splits into five dips-the central unshifted one corresponds to coherent population oscillation, while the outer four are due to CPT. The linewidth of the CPT resonance is about 300 kHz and is limited by the natural linewidth of the excited state, which is to be expected because the excited state is involved in the formation of the dark state.

Controlling the group velocity in a five-level K-type atomic system

The properties of a five-level K-type system are investigated. With the controlling fields, the properties of the dispersion and absorption of the system are changed greatly. The system can produce anomalous dispersion regions with absorption and normal dispersion regions with absorption or transparency. Furthermore, the group velocity can be varied from subluminal to superluminal by varying the intensity of the controlling field and the probe detunings in principle. (C) 2008 Elsevier B.V. All rights reserved.

Six-wave mixing phase-dispersion by optical heterodyne detection in dressed reverse N-type four-level system

We have investigated the dressed effects of non-degenerate four-wave mixing (NDFWM) and demonstrated a phase-sensitive method of studying the fifth-order nonlinear susceptibility due to atomic coherence in RN-type four-level system. In the presence of a strong coupling field, NDFWM spectrum exhibits Autler-Townes splitting, accompanied by either suppression or enhancement of the NDFWM signal, which is directly related to the competition between the absorption and dispersion contributions. The heterodyne-detected nonlinear absorption and dispersion of six-wave mixing signal in the RN-type system show that the hybrid radiation-matter detuning damping oscillation is in the THz range and can be controlled and modified through the colour-locked correlation of twin noisy fields.

Transcriptional coupling between the divergent promoters of a prototypic LysR-type regulatory system, the ilvYC operon of Escherichia coli

The twin-domain model [Liu, L. F. & Wang, J. C. (1987) Proc. Natl. Acad. Sci. USA 84, 7024–7027] suggests that closely spaced, divergent, superhelically sensitive promoters can affect the transcriptional activity of one another by transcriptionally induced negative DNA supercoiling generated in the divergent promoter region. This gene arrangement is observed for many LysR-type-regulated operons in bacteria. We have examined the effects of divergent transcription in the prototypic LysR-type system, the ilvYC operon of Escherichia coli. Double-reporter constructs with the lacZ gene under transcriptional control of the ilvC promoter and the galK gene under control of the divergent ilvY promoter were used to demonstrate that a down-promoter mutation in the ilvY promoter severely decreases in vivo transcription from the ilvC promoter. However, a down-promoter mutation in the ilvC promoter only slightly affects transcription from the ilvY promoter. In vitro transcription assays with DNA topoisomers showed that transcription from the ilvC promoter increases over the entire range of physiological superhelical densities, whereas transcription initiation from the ilvY promoter exhibits a broad optimum at a midphysiological superhelical density. Evidence that this promoter coupling is DNA supercoiling-dependent is provided by the observation that a novobiocin-induced decrease in global negative superhelicity results in an increase in ilvY promoter activity and a decrease in ilvC promoter activity predicted by the in vitro data. We suggest that this transcriptional coupling is important for coordinating basal level expression of the ilvYC operon with the nutritional and environmental conditions of cell growth.

Pinned fronts in heterogeneous media of jump type

In this paper, we analyse the impact of a (small) heterogeneity of jump type on the most simple localized solutions of a 3-component FitzHugh–Nagumo-type system. We show that the heterogeneity can pin a 1-front solution, which travels with constant (non-zero) speed in the homogeneous setting, to a fixed, explicitly determined, distance from the heterogeneity. Moreover, we establish the stability of this heterogeneous pinned 1-front solution. In addition, we analyse the pinning of 1-pulse, or 2-front, solutions. The paper is concluded with simulations in which we consider the dynamics and interactions of N-front patterns in domains with M heterogeneities of jump type (N = 3, 4, M ≥ 1).

Effects of spontaneously induced coherence on absorption of a ladder-type atom

This paper investigates the effects of spontaneously induced coherence on absorption properties in a nearly equispaced three-level ladder-type system driven by two coherent fields. It find that the absorption properties of this system with the probe field applied on the lower transition can be significantly modified if this coherence is optimized. In the case of small spontaneous decay rate in the upper excited state, it finds that such coherence does not destroy the electromagnetically induced transparency (EIT). Nevertheless, the absorption peak on both sides of zero detuning and the linewidth of absorption line become larger and narrower than those in the case corresponding to the effects of spontaneously induced coherence; while in the case of large decay rate, it finds that, instead of EIT with low resonant absorption, a sharp absorption peak at resonance appears. That is, electromagnetically induced absorption in the nearly equispaced ladder-type system can occur due to such coherent effects.

Type-omega DPLs

Type-omega DPLs (Denotational Proof Languages) are languages for proof presentation and search that offer strong soundness guarantees. LCF-type systems such as HOL offer similar guarantees, but their soundness relies heavily on static type systems. By contrast, DPLs ensure soundness dynamically, through their evaluation semantics; no type system is necessary. This is possible owing to a novel two-tier syntax that separates deductions from computations, and to the abstraction of assumption bases, which is factored into the semantics of the language and allows for sound evaluation. Every type-omega DPL properly contains a type-alpha DPL, which can be used to present proofs in a lucid and detailed form, exclusively in terms of primitive inference rules. Derived inference rules are expressed as user-defined methods, which are "proof recipes" that take arguments and dynamically perform appropriate deductions. Methods arise naturally via parametric abstraction over type-alpha proofs. In that light, the evaluation of a method call can be viewed as a computation that carries out a type-alpha deduction. The type-alpha proof "unwound" by such a method call is called the "certificate" of the call. Certificates can be checked by exceptionally simple type-alpha interpreters, and thus they are useful whenever we wish to minimize our trusted base. Methods are statically closed over lexical environments, but dynamically scoped over assumption bases. They can take other methods as arguments, they can iterate, and they can branch conditionally. These capabilities, in tandem with the bifurcated syntax of type-omega DPLs and their dynamic assumption-base semantics, allow the user to define methods in a style that is disciplined enough to ensure soundness yet fluid enough to permit succinct and perspicuous expression of arbitrarily sophisticated derived inference rules. We demonstrate every major feature of type-omega DPLs by defining and studying NDL-omega, a higher-order, lexically scoped, call-by-value type-omega DPL for classical zero-order natural deduction---a simple choice that allows us to focus on type-omega syntax and semantics rather than on the subtleties of the underlying logic. We start by illustrating how type-alpha DPLs naturally lead to type-omega DPLs by way of abstraction; present the formal syntax and semantics of NDL-omega; prove several results about it, including soundness; give numerous examples of methods; point out connections to the lambda-phi calculus, a very general framework for type-omega DPLs; introduce a notion of computational and deductive cost; define several instrumented interpreters for computing such costs and for generating certificates; explore the use of type-omega DPLs as general programming languages; show that DPLs do not have to be type-less by formulating a static Hindley-Milner polymorphic type system for NDL-omega; discuss some idiosyncrasies of type-omega DPLs such as the potential divergence of proof checking; and compare type-omega DPLs to other approaches to proof presentation and discovery. Finally, a complete implementation of NDL-omega in SML-NJ is given for users who want to run the examples and experiment with the language.