Allele resolution of HLA-A using oligonucleotide probes in a two-stage typing strategy

High-resolution polymerase chain reaction using sequence-specific oligonucleotide probes (PCR-SSOP) typing methods for HLA-A identification have been established. The four systems, which operate independently of each other, are intended for use as secondary typing systems following HLA-A identification with a medium-resolution PCR-SSOP technique. The systems, all using digoxigenin-labelled probes, are based on group specific amplifications for resolution of: i) HLA-A*29 & -A*33; ii) HLA-A*24 & -A*30; and iii) HLA-A*26, -A*25, -A*11, -A*34, -A*66 and -A*68 alleles, respectively. The fourth system, for the detection of HLA-A*02 alleles, is a modification of a previously reported PCR-SSOP subtyping system. The methods have been applied to individuals from the local bone marrow registry and HLA-A allele frequencies for the Northern Ireland population have been established.

HLA antigen frequencies and Wegener's granulomatosis

Previous reports of an association between HLA tissue type and Wegener's granulomatosis are contradictory. By using for the first time a highly sensitive restriction fragment-length polymorphism (RFLP) analysis in addition to standard microcytotoxicity assays, the largest series yet investigated (41 patients) was tissue typed. No association was found between any specific HLA antigen and Wegener's granulomatosis. Although the condition appears to be immunologically mediated, this study indicates that the HLA antigens do not have a major role.

A framework for designing robust food supply chains

After years of emphasis on leanness and responsiveness businesses are now experiencing their vulnerability to supply chain disturbances. Although more literature is appearing on this subject, there is a need for an integrated framework to support the analysis and design of robust food supply chains. In this chapter we present such a framework. We define the concept of robustness and classify supply chain disturbances, sources of food supply chain vulnerability, and adequate redesign principles and strategies to achieve robust supply chain performances. To test and illustrate its applicability, the research framework is applied to a meat supply chain.

CD69, CD25, and HLA-DR activation antigen expression on CD3+ lymphocytes and relationship to serum TNF-alpha, IFN-gamma, and sIL-2R levels in aging

Aging is associated with changes in lymphocyte subsets and unexplained HLA-DR upregulation on T-lymphocytes. We further investigated this activation, by measuring early (CD69), middle (CD25), and late (HLA-DR) T-lymphocyte activation markers on CD3+ lymphocytes, across subjects (20-100 years) together with serum tumor necrosis factor (TNF-alpha), interferon-gamma (IFN-gamma), and soluble interleukin-2 receptor (sIL-2R). HLA-DR was present as a CD3+ HLA-DR+ subset that constituted 8% of total lymphocytes, increased twofold with age and included CD4+, CD8+, and CD45RA+ phenotypes. HLA-DR was also expressed on a CD8+ CD57+ subset. The CD3+ CD25+ subset constituted 13% of lymphocytes, fell with age but was weakly associated with the CD3+ HLA-DR+ subset especially in older subjects. A small 3-5% CD3+ CD69+ subsets showed no age effect. Serum sIL-2R, TNF-alpha, but not IFN-gamma, were associated with CD3+ HLA-DR+ lymphocytes, TNF-alpha with CD8+ CD57+ count and sIL-2R and IFN-gamma with the CD3+ CD25+/CD3+ CD4+ ratio. The study confirms age-related upregulation of HLA-DR on CD3+ lymphocytes, shows some evidence for associated upregulation of CD25 on CD3+ cells in older subjects, and links serum TNF-alpha, IFN-gamma, and sIL2-R to T-lymphocyte activation.

Exchange potential from the common energy denominator approximation for the Kohn-Sham Green's function: Application to (hyper)polarizabilities of molecular chains

An approximate Kohn-Sham (KS) exchange potential v(xsigma)(CEDA) is developed, based on the common energy denominator approximation (CEDA) for the static orbital Green's function, which preserves the essential structure of the density response function. v(xsigma)(CEDA) is an explicit functional of the occupied KS orbitals, which has the Slater v(Ssigma) and response v(respsigma)(CEDA) potentials as its components. The latter exhibits the characteristic step structure with "diagonal" contributions from the orbital densities \psi(isigma)\(2), as well as "off-diagonal" ones from the occupied-occupied orbital products psi(isigma)psi(j(not equal1)sigma). Comparison of the results of atomic and molecular ground-state CEDA calculations with those of the Krieger-Li-Iafrate (KLI), exact exchange (EXX), and Hartree-Fock (HF) methods show, that both KLI and CEDA potentials can be considered as very good analytical "closure approximations" to the exact KS exchange potential. The total CEDA and KLI energies nearly coincide with the EXX ones and the corresponding orbital energies epsilon(isigma) are rather close to each other for the light atoms and small molecules considered. The CEDA, KLI, EXX-epsilon(isigma) values provide the qualitatively correct order of ionizations and they give an estimate of VIPs comparable to that of the HF Koopmans' theorem. However, the additional off-diagonal orbital structure of v(xsigma)(CEDA) appears to be essential for the calculated response properties of molecular chains. KLI already considerably improves the calculated (hyper)polarizabilities of the prototype hydrogen chains H-n over local density approximation (LDA) and standard generalized gradient approximations (GGAs), while the CEDA results are definitely an improvement over the KLI ones. The reasons of this success are the specific orbital structures of the CEDA and KLI response potentials, which produce in an external field an ultranonlocal field-counteracting exchange potential. (C) 2002 American Institute of Physics.

Entanglement Spectrum, Critical Exponents and Order Parameters in Quantum Spin Chains

We investigate the entanglement spectrum near criticality in finite quantum spin chains. Using finite size scaling we show that when approaching a quantum phase transition, the Schmidt gap, i.e., the difference between the two largest eigenvalues of the reduced density matrix ?1, ?2, signals the critical point and scales with universal critical exponents related to the relevant operators of the corresponding perturbed conformal field theory describing the critical point. Such scaling behavior allows us to identify explicitly the Schmidt gap as a local order parameter.

Robust food supply supply chains:An integrated framework for vulnerability assessment and disturbance management

The operation of supply chains (SCs) has for many years been focused on efficiency, leanness and responsiveness. This has resulted in reduced slack in operations, compressed cycle times, increased productivity and minimised inventory levels along the SC. Combined with tight tolerance settings for the realisation of logistics and production processes, this has led to SC performances that are frequently not robust. SCs are becoming increasingly vulnerable to disturbances, which can decrease the competitive power of the entire chain in the market. Moreover, in the case of food SCs non-robust performances may ultimately result in empty shelves in grocery stores and supermarkets.
The overall objective of this research is to contribute to Supply Chain Management (SCM) theory by developing a structured approach to assess SC vulnerability, so that robust performances of food SCs can be assured. We also aim to help companies in the food industry to evaluate their current state of vulnerability, and to improve their performance robustness through a better understanding of vulnerability issues. The following research questions (RQs) stem from these objectives:
RQ1: What are the main research challenges related to (food) SC robustness?
RQ2: What are the main elements that have to be considered in the design of robust SCs and what are the relationships between these elements?
RQ3: What is the relationship between the contextual factors of food SCs and the use of disturbance management principles?
RQ4: How to systematically assess the impact of disturbances in (food) SC processes on the robustness of (food) SC performances?
To answer these RQs we used different methodologies, both qualitative and quantitative. For each question, we conducted a literature survey to identify gaps in existing research and define the state of the art of knowledge on the related topics. For the second and third RQ, we conducted both exploration and testing on selected case studies. Finally, to obtain more detailed answers to the fourth question, we used simulation modelling and scenario analysis for vulnerability assessment.
Main findings are summarised as follows.
Based on an extensive literature review, we answered RQ1. The main research challenges were related to the need to define SC robustness more precisely, to identify and classify disturbances and their causes in the context of the specific characteristics of SCs and to make a systematic overview of (re)design strategies that may improve SC robustness. Also, we found that it is useful to be able to discriminate between varying degrees of SC vulnerability and to find a measure that quantifies the extent to which a company or SC shows robust performances when exposed to disturbances.
To address RQ2, we define SC robustness as the degree to which a SC shows an acceptable performance in (each of) its Key Performance Indicators (KPIs) during and after an unexpected event that caused a disturbance in one or more logistics processes. Based on the SCM literature we identified the main elements needed to achieve robust performances and structured them together to form a conceptual framework for the design of robust SCs. We then explained the logic of the framework and elaborate on each of its main elements: the SC scenario, SC disturbances, SC performance, sources of food SC vulnerability, and redesign principles and strategies.
Based on three case studies, we answered RQ3. Our major findings show that the contextual factors have a consistent relationship to Disturbance Management Principles (DMPs). The product and SC environment characteristics are contextual factors that are hard to change and these characteristics initiate the use of specific DMPs as well as constrain the use of potential response actions. The process and the SC network characteristics are contextual factors that are easier to change, and they are affected by the use of the DMPs. We also found a notable relationship between the type of DMP likely to be used and the particular combination of contextual factors present in the observed SC.
To address RQ4, we presented a new method for vulnerability assessments, the VULA method. The VULA method helps to identify how much a company is underperforming on a specific Key Performance Indicator (KPI) in the case of a disturbance, how often this would happen and how long it would last. It ultimately informs the decision maker about whether process redesign is needed and what kind of redesign strategies should be used in order to increase the SC’s robustness. The VULA method is demonstrated in the context of a meat SC using discrete-event simulation. The case findings show that performance robustness can be assessed for any KPI using the VULA method.
To sum-up the project, all findings were incorporated within an integrated framework for designing robust SCs. The integrated framework consists of the following steps: 1) Description of the SC scenario and identification of its specific contextual factors; 2) Identification of disturbances that may affect KPIs; 3) Definition of the relevant KPIs and identification of the main disturbances through assessment of the SC performance robustness (i.e. application of the VULA method); 4) Identification of the sources of vulnerability that may (strongly) affect the robustness of performances and eventually increase the vulnerability of the SC; 5) Identification of appropriate preventive or disturbance impact reductive redesign strategies; 6) Alteration of SC scenario elements as required by the selected redesign strategies and repeat VULA method for KPIs, as defined in Step 3.
Contributions of this research are listed as follows. First, we have identified emerging research areas - SC robustness, and its counterpart, vulnerability. Second, we have developed a definition of SC robustness, operationalized it, and identified and structured the relevant elements for the design of robust SCs in the form of a research framework. With this research framework, we contribute to a better understanding of the concepts of vulnerability and robustness and related issues in food SCs. Third, we identified the relationship between contextual factors of food SCs and specific DMPs used to maintain robust SC performances: characteristics of the product and the SC environment influence the selection and use of DMPs; processes and SC networks are influenced by DMPs. Fourth, we developed specific metrics for vulnerability assessments, which serve as a basis of a VULA method. The VULA method investigates different measures of the variability of both the duration of impacts from disturbances and the fluctuations in their magnitude.
With this project, we also hope to have delivered practical insights into food SC vulnerability. First, the integrated framework for the design of robust SCs can be used to guide food companies in successful disturbance management. Second, empirical findings from case studies lead to the identification of changeable characteristics of SCs that can serve as a basis for assessing where to focus efforts to manage disturbances. Third, the VULA method can help top management to get more reliable information about the “health” of the company.
The two most important research opportunities are: First, there is a need to extend and validate our findings related to the research framework and contextual factors through further case studies related to other types of (food) products and other types of SCs. Second, there is a need to further develop and test the VULA method, e.g.: to use other indicators and statistical measures for disturbance detection and SC improvement; to define the most appropriate KPI to represent the robustness of a complete SC. We hope this thesis invites other researchers to pick up these challenges and help us further improve the robustness of (food) SCs.

Global quantum correlations in finite-size spin chains

We perform an extensive study of the properties of global quantum correlations in finite-size one-dimensional quantum spin models at finite temperature. By adopting a recently proposed measure for global quantum correlations (Rulli and Sarandy 2011 Phys. Rev. A 84 042109), called global discord, we show that critical points can be neatly detected even for many-body systems that are not in their ground state. We consider the transverse Ising model, the cluster-Ising model where three-body couplings compete with an Ising-like interaction, and the nearest-neighbor XX Hamiltonian in transverse magnetic field. These models embody our canonical examples showing the sensitivity of global quantum discord close to criticality. For the Ising model, we find a universal scaling of global discord with the critical exponents pertaining to the Ising universality class.

Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4+ T Cell Immunity

Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

A multiconfigurational time-dependent Hartree-Fock method for excited electronic states. II. Coulomb interaction effects in single conjugated polymer chains

Conjugated polymers have attracted considerable attention in the last few decades due to their potential for optoelectronic applications. A key step that needs optimisation is charge carrier separation following photoexcitation. To understand better the dynamics of the exciton prior to charge separation, we have performed simulations of the formation and dynamics of localised excitations in single conjugated polymer strands. We use a nonadiabatic molecular dynamics method which allows for the coupled evolution of the nuclear degrees of freedom and of multiconfigurational electronic wavefunctions. We show the relaxation of electron-hole pairs to form excitons and oppositely charged polaron pairs and discuss the modifications to the relaxation process predicted by the inclusion of the Coulomb interaction between the carriers. The issue of charge photogeneration in conjugated polymers in dilute solution is also addressed. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3600404]