Telomeres and prognosis in patients with chronic lymphocytic leukaemia

In the present study, telomere length, telomerase activity, the mutation load of immunoglobulin variable heavy chain (IGHV) genes, and established prognostic factors were investigated in 78 patients with chronic lymphocytic leukaemia (CLL) to determine the impact of telomere biology on the pathogenesis of CLL. Telomere length was measured by an automated multi-colour flow-FISH, and an age-independent delta telomere length ( TL) was calculated. CLL with unmutated IGHV genes was associated with shorter telomeres (p = 0.002). Furthermore, we observed a linear correlation between the frequency of IGHV gene mutations and elongation of telomeres (r = 0.509, p < 0.001). With respect to prognosis, a threshold TL of -4.2 kb was the best predictor for progression-free and overall survival. TL was not significantly altered over time or with therapy. The correlation between the mutational load in IGHV genes and the TL in CLL might reflect the initial telomere length of the putative cell of origin (pre- versus post-germinal center B cells). In conclusion, the TL is a reliable prognostic marker for patients with CLL. Short telomeres and high telomerase activity as occurs in some patients with CLL with a worse prognosis might be an ideal target for treatment with telomerase inhibitors.

Performance Characteristics of Airlift Pumps with Vortex Induced by Tangential Fluid Injection

The effect of the swirl component of air injection on the performance of an airlift pump was examined experimentally. An airlift pump is a device that pumps a liquid or slurry using only gas injection. In this study, the liquid used was water and the injected gas was air. The effect of the air swirl was determined by measuring the water discharge from an airlift pump with an air injection nozzle in which the air flow had both axial and tangential components and then repeating the tests with a nozzle with only axial injection. The induced water flow was measured using an orifice meter in the supply pipeline. Tests were run for air pressures ranging from 10 to 30 pounds per square inch, gauge (psig), at flow rates from 5 standard cubic feet per minute (scfm) up the maximum values attainable at the given pressure (usually in the range from 20 to 35 scfm). The nozzle with only axial injection produced a water flow rate that wasequivalent to or better than that induced by the nozzle with swirl. The swirl component of air injection was found to be detrimental to pump performance for all but the smallest air injection flow rate. Optimum efficiency was found for air injection pressures of 10 psig to 15 psig. In addition, the effect of using auxiliary tangential injection of water to create a swirl component in the riser before air injection on the overall capacity (i.e., flow rate) and efficiencyof the pump was examined. Auxiliary tangential water injection was found to have no beneficial effect on the pump capacity or performance in the present system.

The GABRIEL Advanced Surveys: study design, participation and evaluation of bias

Exposure to farming environments has been shown to protect substantially against asthma and atopic disease across Europe and in other parts of the world. The GABRIEL Advanced Surveys (GABRIELA) were conducted to determine factors in farming environments which are fundamental to protecting against asthma and atopic disease. The GABRIEL Advanced Surveys have a multi-phase stratified design. In a first-screening phase, a comprehensive population-based survey was conducted to assess the prevalence of exposure to farming environments and of asthma and atopic diseases (n = 103,219). The second phase was designed to ascertain detailed exposure to farming environments and to collect biomaterial and environmental samples in a stratified random sample of phase 1 participants (n = 15,255). A third phase was carried out in a further stratified sample only in Bavaria, southern Germany, aiming at in-depth respiratory disease and exposure assessment including extensive environmental sampling (n = 895). Participation rates in phase 1 were around 60% but only about half of the participating study population consented to further study modules in phase 2. We found that consenting behaviour was related to familial allergies, high parental education, wheeze, doctor diagnosed asthma and rhinoconjunctivitis, and to a lesser extent to exposure to farming environments. The association of exposure to farm environments with asthma or rhinoconjunctivitis was not biased by participation or consenting behaviour. The GABRIEL Advanced Surveys are one of the largest studies to shed light on the protective 'farm effect' on asthma and atopic disease. Bias with regard to the main study question was able to be ruled out by representativeness and high participation rates in phases 2 and 3. The GABRIEL Advanced Surveys have created extensive collections of questionnaire data, biomaterial and environmental samples promising new insights into this area of research.

AN EXPERIMENTAL EVALUATION OF THE PERFORMANCE OF A VORTEX-DRIVEN AIR LIFT PUMP

A prototype vortex-driven air lift pump was developed and experimentally evaluated. It was designed to be easily manufactured and scalable for arbitrary riser diameters. The model tested fit in a 2 inch diameter riser with six air injection nozzles through which airwas injected helically around the perimeter of the riser at an angle of 70º from pure tangential injection. The pump was intended to transport both water and sediment over a large range of submergence ratios. A test apparatus was designed to be able to simulate deep water or oceanic environments. The resulting test setup had a finite reservoir; over the course of a test, the submergence ratio varied from 0.48 to 0.39. For air injection pressures ranging from 10 to 60 psig and for air flow rates of 6 to 15 scfm, the induced water discharge flow rates varied only slightly, due to the limited range of available submergence ratios. The anticipated simulation of deep water environment, with a corresponding equivalent increase in thesubmergence ratio, proved unattainable. The pump prototype successfully transported both water and sediment (sand). Thepercent volume yield of the sediment was in an acceptable range. The pump design has been subsequently used successfully in a 4 inch configuration in a follow-on project. A computer program was written in Matlab to simulate the pump characteristics. The program output water pressures at the location of air injection which were physicallycompatible with the experimental data.

Integration of computational models and experimental characterization to study internal frost damage in cementitious materials

The objective of this doctoral research is to investigate the internal frost damage due to crystallization pore pressure in porous cement-based materials by developing computational and experimental characterization tools. As an essential component of the U.S. infrastructure system, the durability of concrete has significant impact on maintenance costs. In cold climates, freeze-thaw damage is a major issue affecting the durability of concrete. The deleterious effects of the freeze-thaw cycle depend on the microscale characteristics of concrete such as the pore sizes and the pore distribution, as well as the environmental conditions. Recent theories attribute internal frost damage of concrete is caused by crystallization pore pressure in the cold environment. The pore structures have significant impact on freeze-thaw durability of cement/concrete samples. The scanning electron microscope (SEM) and transmission X-ray microscopy (TXM) techniques were applied to characterize freeze-thaw damage within pore structure. In the microscale pore system, the crystallization pressures at sub-cooling temperatures were calculated using interface energy balance with thermodynamic analysis. The multi-phase Extended Finite Element Modeling (XFEM) and bilinear Cohesive Zone Modeling (CZM) were developed to simulate the internal frost damage of heterogeneous cement-based material samples. The fracture simulation with these two techniques were validated by comparing the predicted fracture behavior with the captured damage from compact tension (CT) and single-edge notched beam (SEB) bending tests. The study applied the developed computational tools to simulate the internal frost damage caused by ice crystallization with the two dimensional (2-D) SEM and three dimensional (3-D) reconstructed SEM and TXM digital samples. The pore pressure calculated from thermodynamic analysis was input for model simulation. The 2-D and 3-D bilinear CZM predicted the crack initiation and propagation within cement paste microstructure. The favorably predicted crack paths in concrete/cement samples indicate the developed bilinear CZM techniques have the ability to capture crack nucleation and propagation in cement-based material samples with multiphase and associated interface. By comparing the computational prediction with the actual damaged samples, it also indicates that the ice crystallization pressure is the main mechanism for the internal frost damage in cementitious materials.

Phenotyping, functional characterization, and developmental changes in canine intestinal intraepithelial lymphocytes

Little is currently known about the lymphocyte populations in the normal and diseased canine gut. The aim of this study was thus the phenotypical and functional characterization of canine intestinal intraepithelial lymphocytes (IEL). IEL were isolated from full-thickness biopsies of 15 adult Swiss Beagle dogs (mean age 8.2 +/-2.8 years) and compared to mesenteric lymph node cells. The phenotypical characterization by multi-parameter flow cytometry revealed that canine IEL differ substantially from lymph node T cells, and consist of various unconventional lymphocyte subsets, unique to mucosal surfaces. These include gammasigma T cells, and CD4(-)CD8(-) and CD8alphaalpha(+) T cells. IEL populations in adult dogs were also compared to those isolated from neonatal Beagle dogs. Analysis revealed a high frequency of undifferentiated CD4(-)CD8(-) T cells in newborn dogs whereas mature CD4(+) and CD8(+) T cells predominate in adult dogs, indicating maturation of the intestinal immune system during development. As IEL in other species are thought to exhibit regulatory functions, we investigated the role of IEL on the activation-induced proliferation of lymph node T cells. While IEL alone did not show activation-induced proliferation, they significantly inhibited the proliferation of activated lymph node T cells in a cell number-dependent manner. These findings are the first to demonstrate that canine intestinal IEL have an immunoregulatory phenotype, which may contribute to the maintenance of intestinal immune homeostasis and may, therefore, be lost in canine chronic enteropathies.

Matching form with content

Successful computer-supported distance education requires that its enabling technologies are accessible and usable anywhere. They should work seamlessly inside and outside the information superhighway, wherever the target learners are located, without obtruding on the learning activity. It has long been recognised that the usability of interactive computer systems is inversely related to the visibility of the implementing technologies. Reducing the visibility of technology is especially challenging in the area of online language learning systems, which require high levels of interactivity and communication along multiple dimensions such as speaking, listening, reading and writing. In this article, the authors review the concept of invisibility as it applies to the design of interactive technologies and appliances. They describe a specialised appliance matched to the requirements for distance second language learning, and report on a successful multi-phase evaluation process, including initial field testing at a Thai open university.

Matching form with content

Successful computer-supported distance education requires that its enabling technologies are accessible and usable anywhere. They should work seamlessly inside and outside the information superhighway, wherever the target learners are located, without obtruding on the learning activity. It has long been recognised that the usability of interactive computer systems is inversely related to the visibility of the implementing technologies. Reducing the visibility of technology is especially challenging in the area of online language learning systems, which require high levels of interactivity and communication along multiple dimensions such as speaking, listening, reading and writing. In this article, the authors review the concept of invisibility as it applies to the design of interactive technologies and appliances. They describe a specialised appliance matched to the requirements for distance second language learning, and report on a successful multi-phase evaluation process, including initial field testing at a Thai open university.

THE ROLE OF MAP KINASES ON THE FUNCTIONAL HETEROGENEITY OF HUMAN CD8+ T CELL MATURATION SUBSETS

While prior studies have focused on naïve (CD45RA+CD27+) and early stage memory (CD45RA-CD27+) CD8+ T cells, late memory CD8+ T cells (CD45RA+CD27) have received less interest because this subset of T cells is generally recognized as effectors, which produce IFNγ (but no IL-2) and perforin. However, multiple studies suggest that late memory CD8+ T cells may provide inadequate protection in infectious diseases and cancer models. To better understand the unique function of late memory CD8+ T cells, I optimized multi-color flow cytometry techniques to assess the cytokine production of each human CD8+ T cell maturation subset. I demonstrated that late memory CD8+ T cells are the predominant producer of CC chemokines (e.g. MIP-1β), but rarely produce IL-2; therefore they do not co-produce IL-2/IFNγ (polyfunctionality), which has been shown to be critical for protective immunity against chronic viral infection. These data suggest that late memory CD8+ T cells are not just cytotoxic effectors, but may have unique functional properties. Determining the molecular signature of each CD8+ T cell maturation subset will help characterize the role of late memory CD8+ T cells. Prior studies suggest that ERK1 and ERK2 play a role in cytokine production including IL-2 in T cells. Therefore, I tested whether differential expression of ERK1 and ERK2 in CD8+ T cell maturation subsets contributes to their functional signature by a novel flow cytometry technique. I found that the expression of total ERK1, but not ERK2, is significantly diminished in late memory CD8+ T cells and that ERK1 expression is strongly associated with IL-2 production and CD28 expression. I also found that IL-2 production is increased in late memory CD8+ T cells by over-expressing ERK1. Collectively, these data suggest that ERK1 is required for IL-2 production in human CD8+ T cells. In summary, this dissertation demonstrated that ERK1 is down-regulated in human late memory CD8+ T cells, leading to decreased production of IL-2. The data in this dissertation also suggested that the functional heterogeneity in human CD8+ T cell maturation subsets results from their differential ERK1 expression.

Pitfalls in post-mortem CT-angiography--intravascular contrast induces post-mortem pericardial effusion

We present a case where multi-phase post-mortem computed tomography angiography (PMCTA) induced a hemorrhagic pericardial effusion during the venous phase of angiography. Post-mortem non-contrast CT (PMCT) suggested the presence of a ruptured aortic dissection. This diagnosis was confirmed by PMCTA after pressure controlled arterial injection of contrast. During the second phase of multi-phase PMCTA the presence of contrast leakage from the inferior cava vein into the pericardial sac was noted. Autopsy confirmed the post-mortem nature of this vascular tear. This case teaches us an important lesson: it underlines the necessity to critically analyze PMCT and PMCTA images in order to distinguish between artifacts, true pathologies and iatrogenic findings. In cases with ambiguous findings such as the case reported here, correlation of imaging findings with autopsy is elementary.

The impact of retrieval processes, age, general achievement level, and test scoring scheme for children's metacognitive monitoring and controlling

This multi-phase study examined the influence of retrieval processes on children’s metacognitive processes in relation to and in interaction with achievement level and age. First, N = 150 9/10- and 11/12-year old high and low achievers watched an educational film and predicted their test performance. Children then solved a cloze test regarding the film content including answerable and unanswerable items and gave confidence judgments to every answer. Finally, children withdrew answers that they believed to be incorrect. All children showed adequate metacognitive processes before and during test taking with 11/12- year-olds outperforming 9/10-year-olds when considering characteristics of on-going retrieval processes. As to the influence of achievement level, high compared to low achievers proved to be more accurate in their metacognitive monitoring and controlling. Results suggest that both cognitive resources (operationalized through achievement level) and mnemonic experience (assessed through age) fuel metacognitive development. Nevertheless, when facing higher demands regarding retrieval processes, experience seems to play the more important role.

Dear Brand, Please Help me to Become a True-Man Out of the Truman: The Role of Brand Authenticity

Although brand authenticity is gaining increasing interest in academia and managerial practice, empirical studies on its contribution to the branding literature are still limited. The authors therefore conceptually and empirically examine the emergence and outcomes of perceived brand authenticity (PBA). A prior multi-phase scale development process resulted in a 17-item PBA scale to measure its four dimensions of credibility, integrity, symbolism, and longevity. Brand authenticity perceptions are influenced by indexical, existential, and iconic cues, whereby the latter’s influence is moderated by consumers’ level of marketing skepticism. Further, PBA increases emotional brand attachment. This relationship is particularly strong for consumers with a high level of self-authenticity. In addition, PBA effects are stronger in a North American market context compared to a European context.

Brand Authenticity: An Integrative Framework and Measurement Scale

This article develops an integrative framework of the concept of perceived brand authenticity (PBA) and sheds light on PBA’s (1) measurement, (2) drivers, (3) consequences, as well as (4) an underlying process of its effects and (5) boundary conditions. A multi-phase scale development process resulted in a 15-item PBA scale to measure its four dimensions of credibility, integrity, symbolism, and continuity. PBA is influenced by indexical, existential, and iconic cues, whereby the latter’s influence is moderated by consumers’ level of marketing skepticism. Results also suggest that PBA drives brand choice likelihood through self-congruence for consumers high in self-authenticity.

Brand Authenticity: An Integrative Framework and Measurement Scale

Although brand authenticity is gaining increasing interest in consumer behavior research and managerial practice, literature on its measurement and contribution to branding theory is still limited. This article develops an integrative framework of the concept of brand authenticity and reports the development and validation of a scale measuring consumers' perceived brand authenticity (PBA). A multi-phase scale development process resulted in a 15-item PBA scale measuring four dimensions: credibility, integrity, symbolism, and continuity. This scale is reliable across different brands and cultural contexts. We find that brand authenticity perceptions are influenced by indexical, existential, and iconic cues, whereby some of the latters' influence is moderated by consumers' level of marketing skepticism. Results also suggest that PBA increases emotional brand attachment and word-of-mouth, and that it drives brand choice likelihood through self-congruence for consumers high in self-authenticity.

Brand Authenticity: an Integrative Framework

Although brand authenticity is gaining increasing interest in consumer behavior research and managerial practice, literature on its measurement and contribution to branding theory is still limited. This article develops an integrative framework of the concept of brand authenticity and reports the development and validation of a scale measuring consumers' perceived brand authenticity (PBA). A multi-phase scale development process resulted in a 15-item PBA scale measuring four dimensions: credibility, integrity, symbolism, and continuity. This scale is reliable across different brands and cultural contexts. We find that brand authenticity perceptions are influenced by indexical, existential, and iconic cues, whereby some of the latters' influence is moderated by consumers' level of marketing skepticism. Results also suggest that PBA increases emotional brand attachment and word-of-mouth, and that it drives brand choice likelihood through self-congruence for consumers high in self-authenticity.