Background: Breast and endometrial cancers are the most common gynaecological cancers in women in the UK. Early detection of tumours is crucial for improving patient survival rates. In breast cancer, mammography is the most reliable screening method for asymptomatic patients; however, its sensitivity is limited by breast density. Currently, there are no early screening assays for endometrial cancer. Thus, there is an urgent need to identify clinical biomarkers for improved non-invasive diagnosis of breast and endometrial cancer. Macrophages are abundant in the tumour microenvironment and their density has been associated with poor prognosis in breast cancer and decreased survival in endometrial cancer. Monocytes are precursors of macrophages and recent studies have shown an association with pro-tumoral functions. The aim of this study has been to examine the transcriptional profiles of human circulating monocytes and tumour associated macrophages (TAMs) in order to investigate their biological relevance and potential as biomarkers for cancer detection and prognosis. Methods: RNA-sequencing was performed on purified monocytes (22 healthy individuals, 21 breast cancer, 16 endometrial cancer samples), as well as purified normal macrophages, TAMs from breast tissue (4 breast cancer, 4 healthy breast) and endometrium tissue (5 endometrial cancer, 9 healthy endometrium). Results: A shift in the transcriptional profile of monocytes in cancer compared to controls was observed. Given these cancer-associated alterations circulating monocytes from cancer patients were called “Tumour Educated Monocytes” (TEMo). A TEMo-derived 13-gene signature was extracted that detected cancer, yielding an accuracy of 94%, a positive predictive value (PPV) of 92% and a negative predictive value (NPV) of 97%. External validation confirmed the ability of the signature to accurately identify cancer patients with perfect accuracy. Transcriptome profiling of TAMs revealed a significantly altered gene expression profile when compared to normal tissue resident macrophages. Furthermore, comparison of TAMs between breast and endometrial cancer also revealed differences suggesting that different tumour microenvironments induce different gene expression profiles in TAMs. Functional analysis of significant genes in breast cancer revealed similar biological pathways to those of murine studies suggesting that TAMs in humans and mice may have similar functions. A gene list of transmembrane receptors has been extracted by comparing breast cancer TAMs with publicly available datasets that could serve as markers for their identification. Finally, exploratory analysis identified a subset of 49 genes associated with recurrence-free and overall survival in publicly available datasets. Conclusion: To my knowledge this is the first genome-wide profiling study of human circulating monocytes and TAMs in breast and endometrial cancer. It provides evidence that monocytes and TAMs can alter their expression profile in the presence of cancer and, using bioinformatics tools I was able to identify biomarkers for diagnosis and prognosis of breast and endometrial cancer.

<p>Bronchial carcinois are subdivided into typical and atypical. Atypical carcinoids are more malignant, but typical carcinoids may also influence survival. In the present study immunohistochemistry was performed to identify prognostic markets in patients with typical bronchial carcinoids. The diagnostic efficacy of octreoscan was evaluated, in comparison with CT and bone scan, and finally our experience of treating patients with metastatic bronchial carcinoids is reported. In an unselected material of 43 patients with typical bronchial carcinoids, metastatic disease was found in 12 patients (28%). Five patients (12%) developed distant metastases and died from their disease. High Ki-67 index, as well as positive staining for bcl-2 or p53 was associated with de- creased survival time. Positive staining for CD44s, v7-8 and v9, as well as positive nuclear staining for nm23 correlated to decreased mortality. Staining for CD44 and Ki-67 should be performed routinely for prognostic evaluation in these patients. </p><p>Octreoscan positive tumors were found in altogether 20/28 patients (71%). The primary tumor was detectable in 81% and intrathoracic metastases in 78% of the patients on octreoscan; the corresponding figures for CT were 94% and 89% respectively. Liver metastases, as shown by CT, were demonstable by octreoscan in 64% of patients. Octreoscan showed 70% and bone scan 90% sensitivity for identification of bone metastases. </p><p>Plasma chromogranin A was elevated in 28/30 patients (94%) with metastatic bronchial carcinoids and was the most sensitive tumor marker. Increased urinary 5'HIAA was found in 68%. </p><p>Biotherapy with α-interferon and Octreotide relieved carcinoid syndrome in 7/16 patients. However, only 4/27 patients showed stable disease during median 15 months, while 23 patients progressed. Treatment with cisplatinum + etoposide resulted in an objective response or stable disease for 6-8 months in 3/8 patients with widespread tumors. Doxorubicin combined with streptozotocin or paclitaxel was associated with stable disease for 9 months in 2/2 patients each. All 7 patients treated with streptozotocin+5-FU progressed. </p><p>Among the 43 unselected typical bronchial carcinoid patients, 5-year and 10-year survival was 95% and 91%, respectively. The prognosis in patients with bronchial carcinoids showing distant metastases was poor: 5-year survival was 70% from diagnosis and 22% from treatment start. </p>

Bronchial carcinois are subdivided into typical and atypical. Atypical carcinoids are more malignant, but typical carcinoids may also influence survival. In the present study immunohistochemistry was performed to identify prognostic markets in patients with typical bronchial carcinoids. The diagnostic efficacy of octreoscan was evaluated, in comparison with CT and bone scan, and finally our experience of treating patients with metastatic bronchial carcinoids is reported. In an unselected material of 43 patients with typical bronchial carcinoids, metastatic disease was found in 12 patients (28%). Five patients (12%) developed distant metastases and died from their disease. High Ki-67 index, as well as positive staining for bcl-2 or p53 was associated with de- creased survival time. Positive staining for CD44s, v7-8 and v9, as well as positive nuclear staining for nm23 correlated to decreased mortality. Staining for CD44 and Ki-67 should be performed routinely for prognostic evaluation in these patients. Octreoscan positive tumors were found in altogether 20/28 patients (71%). The primary tumor was detectable in 81% and intrathoracic metastases in 78% of the patients on octreoscan; the corresponding figures for CT were 94% and 89% respectively. Liver metastases, as shown by CT, were demonstable by octreoscan in 64% of patients. Octreoscan showed 70% and bone scan 90% sensitivity for identification of bone metastases. Plasma chromogranin A was elevated in 28/30 patients (94%) with metastatic bronchial carcinoids and was the most sensitive tumor marker. Increased urinary 5'HIAA was found in 68%. Biotherapy with α-interferon and Octreotide relieved carcinoid syndrome in 7/16 patients. However, only 4/27 patients showed stable disease during median 15 months, while 23 patients progressed. Treatment with cisplatinum + etoposide resulted in an objective response or stable disease for 6-8 months in 3/8 patients with widespread tumors. Doxorubicin combined with streptozotocin or paclitaxel was associated with stable disease for 9 months in 2/2 patients each. All 7 patients treated with streptozotocin+5-FU progressed. Among the 43 unselected typical bronchial carcinoid patients, 5-year and 10-year survival was 95% and 91%, respectively. The prognosis in patients with bronchial carcinoids showing distant metastases was poor: 5-year survival was 70% from diagnosis and 22% from treatment start.

In insects, hemocytes are considered as the only source of plasma prophenoloxidase (PPO). PPO also exists in the hemocytes of the hematopoietic organ that is connected to the wing disc of Bombyx mori. It is unknown whether there are other cells or tissues that can produce PPO and release it into the hemolymph besides circulating hemocytes. In this study, we use the silkworm as a model to explore this possibility. Through tissue staining and biochemical assays, we found that wing discs contain PPO that can be released into the culture medium in vitro. An in situ assay showed that some cells in the cavity of wing discs have PPO1 and PPO2 mRNA. We conclude that the hematopoietic organ may wrongly release hemocytes into wing discs since they are connected through many tubes as repost in previous paper. In wing discs, the infiltrating hemocytes produce and release PPO probably through cell lysis and the PPO is later transported into hemolymph. Therefore, this might be another source of plasma PPO in the silkworm: some infiltrated hemocytes sourced from the hematopoietic organ release PPO via wing discs.

In cardiovascular disease the repair response is insufficient to restore blood flow, leading to the death of muscle and loss of tissue function. Therefore, strategies to augment the endogenous cell response and its effects may help improve tissue recovery and function. In this study we explored the use of tissue-engineered collagen matrices for augmenting endogenous regenerative processes after myocardial infarction. Treatment with the sLeX-collagen matrix reduced inflammation and apoptosis and had a positive regenerative effect on the infarcted mouse heart, through improved vascular density and possibly enhanced cardiomyogenesis. Additionally, we investigated the effects of cryopreservation on generating circulating angiogenic cells (CACs) from peripheral blood mononuclear cells (PBMCs), as a potential source of stem cells that could be used in combination with our collagen scaffold. Our findings show that despite PBMCs experiencing phenotypic changes after cryopreservation, they may still be used to generate the same therapeutic CACs as freshly procured PBMCs.

Angiogenic cell therapy is currently being developed as a treatment for coronary artery disease (CAD); however, endothelial dysfunction (ED), commonly found in patients with CAD, impairs the ability for revascularization to occur. We hypothesized that culture on a collagen matrix will improve survival and function of circulating progenitor cells (CPCs) isolated from a mouse model of ED. Overall, ED decreased the expression of endothelial markers in CPCs and impaired their function, compared to normal mice. Culture of CPCs from ED mice on collagen was able to increase cell marker expression, and improve migration and adhesion potential, compared to CPCs on fibronectin. Nitric oxide production was reduced for CPCs on collagen for the ED group; however, CPCs on collagen had better viability under conditions of serum deprivation and hypoxia, compared to fibronectin. This study suggests that a collagen matrix may improve the function of therapeutic CPCs that have been exposed to ED.

Many particulate processes are preferably implemented in circulating fluidized beds (CFB) over traditional low-velocity fluidization to take advantage of the many benefits of circulating systems. Fluid catalytic cracking (FCC) is one of the most successfully applied processes in CFB technology, with more than 350 FCC units in operation worldwide. Despite its extensive use, an understanding of the complex behaviour of these units is incomplete.<p> A theoretical and experimental evaluation of the fluidization behaviour was conducted in the CFB riser, standpipe, and stripper. Initially, an extension of the existing CFB in the Fluidization Laboratory of Saskatchewan was designed. The experimental program conducted in this study included an examination of the solids flow behaviour in the riser, interstitial gas velocity in the downcomer, and stripping efficiency measurements. The hydrodynamic behaviour of the stripper was modeled using Multiphase Flow with Interphase eXchanges (MFIX) CFD code.<p> The solids flow behaviour in the bottom zone of a high-density riser was investigated by measuring the local upwards and downwards solids flux. Solids circulation rates between 125 and 243 kg/(m2⋅s) were evaluated at a constant riser superficial gas velocity of 5.3 m/s. The effect of the riser superficial gas velocity of the local upflow at the riser centerline was also conducted at a solids circulation rate of 187 kg/(m2⋅s). The results show that there is little variation in the local net solids flux at radial locations between 0.00 ¡Ü r/R ¡Ü 0.87. The results indicate that a sharp regime change from a typical parabolic solids flux profile to this more radially uniform solids flux profile occurs at a gas velocity between 4.8 and 4.9 m/s.<p> To quantify stripping efficiency, the underflow of an injected tracer into the standpipe must be known. Quantification of the underflow into the standpipe requires knowledge of two main variables: the interstitial gas velocity and the tracer gas concentration profiles in the standpipe. Stripping efficiency was determined for stripper solids circulation rates of 44, 60, and 74 kg/(m2⋅s) and gas velocities of 0.1, 0.2, and 0.3 m/s. For most conditions studied, the interstitial gas velocity profile was found to be flat for both fluidized and packed bed flow. The stripping efficiency was found to be sensitive to the operating conditions. The highest efficiency is attained at low solids circulation rates and high stripping gas velocities.<p> In the numeric study, stripper hydrodynamics were examined for similar operating conditions as those used in the experimental program. Due to an improved radial distribution of gas and decreasing bubble rise velocity, mass transfer is deemed most intense as bubbles crest above the baffles into the interspace between disc and donut baffles. Stripping efficiency is thought to improve with increasing gas velocity due to an increased bubbling frequency. Stripping efficiency is thought to decrease with increasing solids circulation rates due to a lower emulsion-cloud gas interchange coefficient and a decreased residence time of the emulsion in the stripper.

Se estudió la incidencia de déficits del sistema complemento en pacientes con enfermedad meningocócica, detectándose 4 pacientes con déficit completo en la actividad hemolítica mediada por el complemento (ensayo de CH50). Tres de ellos tenían un déficit completo del factor C8, dos de los cuales pertenecían a la misma familia, y el cuarto paciente presentaba un déficit parcial de C3, secundario a la presencia de un factor activador de la vía alterna del complemento, conocido con factor nefrítico, o C3-nef. En los casos con déficit de C8 se llevó a cabo un estudio familiar, detectándose otro individuo más con déficit de C( y nueve sujetos con déficit parcial (inviduos heterocigotos). Así mismo se analizaron los niveles de complejos inmunes circulantes, mediante dos tecnicas diferentes: la fijación a C1q y la unión a células Raji. Los resultados no muestran asociación entre los niveles de CIC y la severidad del cuadro clínico. / We analyzed the incidence of complement deficiencies in patients with acute meningocococcal disease. We detected four patients with recurrent meningococcal infections having a complete lack of serum haemolitical activity (CH50 assay). Three of then had a complete absence of CD8 in serum and the four patient had an aberrant activation of the alternative complement pathway due to the presence of C3-nef. Familial studies were done in the cases of C8 deficiencies, in which a fourth member was identified, together with nine individuals with a partial (heterocygotic) C8 deficiency. Finally we evaluated the levels of circulating immune complexes (CIC) by binding to C1q or to Raji cells. Our results showed a lack of association between the severity of the disease and the levels of CIC.

Many particulate processes are preferably implemented in circulating fluidized beds (CFB) over traditional low-velocity fluidization to take advantage of the many benefits of circulating systems. Fluid catalytic cracking (FCC) is one of the most successfully applied processes in CFB technology, with more than 350 FCC units in operation worldwide. Despite its extensive use, an understanding of the complex behaviour of these units is incomplete.<p> A theoretical and experimental evaluation of the fluidization behaviour was conducted in the CFB riser, standpipe, and stripper. Initially, an extension of the existing CFB in the Fluidization Laboratory of Saskatchewan was designed. The experimental program conducted in this study included an examination of the solids flow behaviour in the riser, interstitial gas velocity in the downcomer, and stripping efficiency measurements. The hydrodynamic behaviour of the stripper was modeled using Multiphase Flow with Interphase eXchanges (MFIX) CFD code.<p> The solids flow behaviour in the bottom zone of a high-density riser was investigated by measuring the local upwards and downwards solids flux. Solids circulation rates between 125 and 243 kg/(m2⋅s) were evaluated at a constant riser superficial gas velocity of 5.3 m/s. The effect of the riser superficial gas velocity of the local upflow at the riser centerline was also conducted at a solids circulation rate of 187 kg/(m2⋅s). The results show that there is little variation in the local net solids flux at radial locations between 0.00 ¡Ü r/R ¡Ü 0.87. The results indicate that a sharp regime change from a typical parabolic solids flux profile to this more radially uniform solids flux profile occurs at a gas velocity between 4.8 and 4.9 m/s.<p> To quantify stripping efficiency, the underflow of an injected tracer into the standpipe must be known. Quantification of the underflow into the standpipe requires knowledge of two main variables: the interstitial gas velocity and the tracer gas concentration profiles in the standpipe. Stripping efficiency was determined for stripper solids circulation rates of 44, 60, and 74 kg/(m2⋅s) and gas velocities of 0.1, 0.2, and 0.3 m/s. For most conditions studied, the interstitial gas velocity profile was found to be flat for both fluidized and packed bed flow. The stripping efficiency was found to be sensitive to the operating conditions. The highest efficiency is attained at low solids circulation rates and high stripping gas velocities.<p> In the numeric study, stripper hydrodynamics were examined for similar operating conditions as those used in the experimental program. Due to an improved radial distribution of gas and decreasing bubble rise velocity, mass transfer is deemed most intense as bubbles crest above the baffles into the interspace between disc and donut baffles. Stripping efficiency is thought to improve with increasing gas velocity due to an increased bubbling frequency. Stripping efficiency is thought to decrease with increasing solids circulation rates due to a lower emulsion-cloud gas interchange coefficient and a decreased residence time of the emulsion in the stripper.

A dynamic mathematical model for simulation of atmospheric circulating fluidized bed combustors has been developed on the basis of first principles and empirical correlations. The model accounts for dense and dilute zone hydrodynamics, volatiles release and combustion, char particles combustion and their size distribution, and heat transfer from/to gas, particles, waterwalls and refractory. Inputs to the model include configuration and dimensions of the combustor and its internals, air and coal flows, coal analysis, all solid and gas properties, inlet temperatures of air, cooling water, and feed solids, size distribution of feed solids / whereas outputs include transient values of combustor temperatures, gas concentrations, char and inert hold-ups and their size distributions. The solution procedure employs method of lines approach for the governing non-linear partial differential equations and combined bisection and secant rule for non-linear algebraic equations. The initial conditions required for the model are provided from the simultaneous solution of governing equations of dynamic model with all temporal derivatives set to zero. By setting all temporal derivatives to zero, model can also be utilized for steady state performance prediction. In order to assess the validity and predictive accuracy of the model, it was applied to the prediction of the steady state behavior of Technical University of Nova Scotia 0.3 MWt CFBC Test Rig and predictions were compared with measurements taken on the same rig. Comparison of model predictions at steady state conditions revealed that the predictions of the model are physically correct and agree well with the measurements and the model is successful in qualitatively and quantitatively simulating the processes taking place in a circulating fluidized bed combustor.