Combined radioimmunotherapy and chemotherapy of human colon carcinoma grafted in nude mice, advantages and limitations.

In order to determine if 5-fluorouracil (5FU) could potentiate the effect of radioimmunotherapy (RIT), nude mice bearing subcutaneous human colon carcinoma xenografts were treated by 1 or 2 intravenous injection(s) of subtherapeutic doses of 131I labeled F(ab')2 from anti-carcinoembryonic antigen monoclonal antibodies combined with 5 daily intraperitoneal injections of 5FU. Control mice received either 131I F(ab')2 alone, 5FU alone or no treatment. RIT alone induced significant tumor regression, while 5FU alone gave only minimal tumor growth inhibition. The combined treatment group also resulted in long-term tumor regression with tumors remaining significantly smaller than in the RIT alone group. There was however, no significant difference in tumor recurrence time between the groups treated with RIT alone or with RIT + 5FU. Myelotoxicity, the major side effect of RIT, detected by the decrease of peripheral white blood cells (WBC), was shown to be almost identical between the groups receiving only RIT or only 5FU. Surprisingly, there was no cumulative bone marrow toxicity in animals which received 5FU before RIT. Furthermore, in the latter group, the WBC levels after RIT were significantly higher than in the control group receiving only RIT. Taken together, the results demonstrate the higher therapeutic efficiency of RIT as compared to 5FU in this model. They do not show, however, that the combination of the two forms of treatment can induce longer tumor remission. Interestingly, the WBC results suggest that 5FU given before RIT can have a radioprotective effect on bone marrow, possibly by selecting radioresistant bone marrow stem cells.

Expanding Combined Heat and Power in Iowa, October 2015

Combined Heat and Power (CHP) refers to the onsite production of electricity and thermal energy from the same fuel source. Integrating power and thermal energy production is more efficient than separate generating systems and used in the right situation can yield several benefits.

Combined Heat and Power Resource Guide, December 2015

Combined Heat and Power (CHP) refers to the onsite production of electricity and thermal energy from the same fuel source. Integrating power and thermal energy production is more efficient than separate generating systems and used in the right situation can yield several benefits.

Chemical chaperones regulate molecular chaperones in vitro and in cells under combined salt and heat stresses.

Salt and heat stresses, which are often combined in nature, induce complementing defense mechanisms. Organisms adapt to high external salinity by accumulating small organic compounds known as osmolytes, which equilibrate cellular osmotic pressure. Osmolytes can also act as "chemical chaperones" by increasing the stability of native proteins and assisting refolding of unfolded polypeptides. Adaptation to heat stress depends on the expression of heat-shock proteins, many of which are molecular chaperones, that prevent protein aggregation, disassemble protein aggregates, and assist protein refolding. We show here that Escherichia coli cells preadapted to high salinity contain increased levels of glycine betaine that prevent protein aggregation under thermal stress. After heat shock, the aggregated proteins, which escaped protection, were disaggregated in salt-adapted cells as efficiently as in low salt. Here we address the effects of four common osmolytes on chaperone activity in vitro. Systematic dose responses of glycine betaine, glycerol, proline, and trehalose revealed a regulatory effect on the folding activities of individual and combinations of chaperones GroEL, DnaK, and ClpB. With the exception of trehalose, low physiological concentrations of proline, glycerol, and especially glycine betaine activated the molecular chaperones, likely by assisting local folding in chaperone-bound polypeptides and stabilizing the native end product of the reaction. High osmolyte concentrations, especially trehalose, strongly inhibited DnaK-dependent chaperone networks, such as DnaK+GroEL and DnaK+ClpB, likely because high viscosity affects dynamic interactions between chaperones and folding substrates and stabilizes protein aggregates. Thus, during combined salt and heat stresses, cells can specifically control protein stability and chaperone-mediated disaggregation and refolding by modulating the intracellular levels of different osmolytes.

Cost-effectiveness of a new combined immunosuppressive and anti-infectious regimen in kidney transplantation.

OBJECTIVES: The aims of this study were to assess the 1-year cost-effectiveness of a new combined immunosuppressive and anti-infectious regimen in kidney transplantation to prevent both rejection and infectious complications. METHODS: Patients (pts) transplanted from January 2000 to March 2003 (Group A) and treated with a conventional protocol were compared with pts submitted to a combined regimen including universal cytomegalovirus (CMV) prophylaxis between April 2003 and July 2005 (Group B). Costs were computed from the hospital accounting system for hospital stays, and official tariffs for outpatient visits. Patients with incomplete costs data were excluded from analysis. RESULTS: Fifty-three patients were analyzed in Group A, and 60 in Group B. Baseline characteristics including CMV serostatus were not significantly different between the two groups. Over 12 months after transplantation, acute rejections decreased from 41.5 percent in Group A to 6.7 percent in Group B (p < .001), and CMV infections from 47 percent to 15 percent (p < .001). Overall, readmissions decreased from 68 percent to 55 percent (p = .160), and average hospital days from 28 +/- 19 to 20 +/- 11 days (p < .007). The average number of outpatient visits decreased from 49 +/- 10 to 39 +/- 8 (p < .001). Average 1-year immunosuppressive and CMV prophylaxis costs (per patient) increased from CHF20,402 +/- 7,273 to 27,375 +/- 6,063 (p < .001), graft rejection costs decreased from CHF4,595 +/- 10,182 to 650 +/- 3,167 (p = .005), CMV treatment costs from CHF2,270 +/- 6,161 to 101 +/- 326 (p = .008), and outpatient visits costs from CHF8,466 +/- 1'721 to 6,749 +/- 1,159 (p < .001). Altogether, 1-year treatment costs decreased from CHF39'957 +/- 16,573 to 36,204 +/- 6,901 (p = .115). CONCLUSIONS: The new combined regimen administered in Group B was significantly more effective, and its additional costs were more than offset by savings associated with complications avoidance.

Combined transcriptomic and proteomic studies reveal non-canonical signaling functions in the jasmonate pathway

Abstract Lipid derived signals mediate many stress and defense responses in multicellular eukaryotes. Among these are the jasmonates, potently active signaling compounds in plants. Jasmonic acid (JA) and 12-oxo-phytodienoic acid (OPDA) are the two best known members of the large jasmonate family. This thesis further investigates their roles as signals using genomic and proteomic approaches. The study is based on a simple genetic model involving two key genes. The first is ALLENE OXIDE SYNTHASE (AOS), encoding the most important enzyme in generating jasmonates. The second is CORONATINE INSENSITIVE 1 (COI1), a gene involved in all currently documented canonical signaling responses. We asked the simple question: do null mutations in AOS and COI1 have analogous effects on the transcriptome ? We found that they do not. If most COI1-dependent genes were also AOS-dependent, the expression of a zinc-finger protein was AOS-dependent but was unaffected by the coi1-1 mutation. We thus supposed that a jasmonate member, most probably OPDA, can alter gene expression partially independently of COI1. Conversely, the expression of at least three genes, one of these is a protein kinase, was shown to be COI1-dependent but did not require a functional AOS protein. We conclude that a non-jasmonate signal might alter gene expression through COIL Proteomic comparison of coi1-1 and aos plants confirmed these observations and highlighted probable protein degradation processes controlled by jasmonates and COI1 in the wounded leaf. This thesis revealed new functions for COI1 and for AOS-generated oxylipins in the jasmonate signaling pathway. Résumé Les signaux dérivés d'acides gras sont des médiateurs de réponses aux stress et de la défense des eucaryotes multicellulaires. Parmi eux, les jasmonates sont de puissants composés de sig¬nalisation chez les plantes. L'acide jasmonique (JA) et l'acide 12-oxo-phytodienoïc (OPDA) sont les deux membres les mieux caractérisés de la grande famille des jasmonates. Cette thèse étudie plus profondément leurs rôles de signalisation en utilisant des approches génomique et protéomique. Cette étude est basée sur un modèle génétique simple n'impliquant que deux gènes. Le premier est PALLENE OXYDE SYNTHASE (AOS) qui encode l'enzyme la plus importante pour la fabrication des jasmonates. Le deuxième est CORONATINE INSENSITIVE 1 (COI1) qui est impliqué dans la totalité des réponses aux jasmonates connues à ce jour. Nous avons posé la question suivante : est-ce que les mutations nulles dans les gènes AOS et COI1 ont des effets analogues sur le transcriptome ? Nous avons trouvé que ce n'était pas le cas. Si la majorité des gènes dépendants de COI1 sont également dépendants d'AOS, l'expression d'un gène codant pour une protéine formée de doigts de zinc n'est pas affectée par la mutation de COI1 tout en étant dépendante d'AOS. Nous avons donc supposé qu'un membre de la famille des jasmonates, probablement OPDA, pouvait modifier l'expression de certains gènes indépendamment de COI1. Inversement, nous avons montré que, tout en étant dépendante de COI1, l'expression d'au moins trois gènes, dont un codant pour une protéine kinase, n'était pas affectée par l'absence d'une protéine AOS fonctionnelle. Nous en avons conclu qu'un signal autre qu'un jasmonate devait modifier l'expression de certains gènes à travers COI1. La comparaison par protéomique de plantes aos et coi1-1 a confirmé ces observations et a mis en évidence un probable processus de dégradation de protéines contrôlé par les jasmonates et COU_ Cette thèse a mis en avant de nouvelles fonctions pour COI1 et pour des oxylipines générées par AOS dans le cadre de la signalisation par les jasmonates.

Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation.

Stromal fibroblast senescence has been linked to ageing-associated cancer risk. However, density and proliferation of cancer-associated fibroblasts (CAFs) are frequently increased. Loss or downmodulation of the Notch effector CSL (also known as RBP-Jκ) in dermal fibroblasts is sufficient for CAF activation and ensuing keratinocyte-derived tumours. We report that CSL silencing induces senescence of primary fibroblasts from dermis, oral mucosa, breast and lung. CSL functions in these cells as a direct repressor of multiple senescence- and CAF-effector genes. It also physically interacts with p53, repressing its activity. CSL is downmodulated in stromal fibroblasts of premalignant skin actinic keratosis lesions and squamous cell carcinomas, whereas p53 expression and function are downmodulated only in the latter, with paracrine FGF signalling as the probable culprit. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effectors and promotes stromal and cancer cell expansion. The findings support a CAF activation-stromal co-evolution model under convergent CSL-p53 control.

Combined dielectrophoretic and impedance system for on-chip controlled bacteria concentration: Application to Escherichia coli

The present paper reports a bacteria autonomous controlled concentrator prototype with a user-friendly interface for bench-top applications. It is based on a micro-fluidic lab-on-a-chip and its associated custom instrumentation, which consists in a dielectrophoretic actuator, to pre-concentrate the sample, and an impedance analyser, to measure concentrated bacteria levels. The system is composed by a single micro-fluidic chamber with interdigitated electrodes and a instrumentation with custom electronics. The prototype is supported by a real-time platform connected to a remote computer, which automatically controls the system and displays impedance data used to monitor the status of bacteria accumulation on-chip. The system automates the whole concentrating operation. Performance has been studied for controlled volumes of Escherichia coli (E. coli) samples injected into the micro-fluidic chip at constant flow rate of 10 μL/min. A media conductivity correcting protocol has been developed, as the preliminary results showed distortion of the impedance analyser measurement produced by bacterial media conductivity variations through time. With the correcting protocol, the measured impedance values were related to the quantity of bacteria concentrated with a correlation of 0.988 and a coefficient of variation of 3.1%. Feasibility of E. coli on-chip automated concentration, using the miniaturized system, has been demonstrated. Furthermore, the impedance monitoring protocol had been adjusted and optimized, to handle changes in the electrical properties of the bacteria media over time.

Combined electromagnetic and thermal design platform for totally enclosed induction machines

The aim of the thesis is to design a suitable thermal model that can be used as a tool for constructing the TEFC squirrel cage induction machine in addition to the electromagnetic model. A lumped-parameter thermal model is developed. The related problems and aspects of implementation are discussed in details. Losses are calculated analytically and the loss values are used in the thermal model. The sensitivity analysis is introduced to determine the most critical parameters of the model.

Hemodynamic and hormonal actions of adrenomedullin

Adrenomedullin, a 52-amino acid residue peptide, has numerous biological actions which are of potential importance to cardiovascular homeostasis, growth and development of cardiovascular tissues and bone, prevention of infection, and regulation of body fluid and electrolyte balance. Studies in man using intravenous infusion of the peptide have demonstrated that, at plasma levels detected after myocardial infarction or in heart failure, adrenomedullin reduces arterial pressure, increases heart rate and cardiac output, and activates the sympathetic and renin-angiotensin systems but suppresses aldosterone. The thresholds for these responses differ, being lower under some experimental circumstances for arterial pressure than for the other biological effects. Adrenomedullin administration inhibits the pressor and aldosterone-stimulating action of angiotensin II in man. By contrast, the pressor effect of norepinephrine is little altered by concomitant adrenomedullin administration. Although in the absence of a safe, specific antagonist of the actions of endogenous adrenomedullin it is difficult to be certain about the physiological and pathophysiological importance of this peptide in man, current evidence suggests that it serves to protect against cardiovascular overload and injury. Hope has been expressed that adrenomedullin or an agonist specific for adrenomedullin receptors might find a place in the treatment of cardiovascular disorders.

Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK) and L-arginine treatment both alone and in combination on blood pressure (BP), and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C) hypertension, 2K1C+ALSK (ALSK), 2K1C+L-arginine (L-arg), and 2K1C+ALSK+L-arginine (ALSK+L-arg) treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME) increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

Effects of combined electric and acoustic hearing on speech perception of a pediatric cochlear implant user

The primary objective of this study was to document the benefits and possible detriments of combining ipsilateral acoustic hearing in the cochlear implant ear of a patient with preserved low frequency residual hearing post cochlear implantation. The secondary aim was to examine the efficacy of various cochlear implant mapping and hearing aid fitting strategies in relation to electro-acoustic benefits.

Velocities of compressional and shear waves in limestones

Carbonate rocks are important hydrocarbon reservoir rocks with complex textures and petrophysical properties (porosity and permeability) mainly resulting from various diagenetic processes (compaction, dissolution, precipitation, cementation, etc.). These complexities make prediction of reservoir characteristics (e.g. porosity and permeability) from their seismic properties very difficult. To explore the relationship between the seismic, petrophysical and geological properties, ultrasonic compressional- and shear-wave velocity measurements were made under a simulated in situ condition of pressure (50 MPa hydrostatic effective pressure) at frequencies of approximately 0.85 MHz and 0.7 MHz, respectively, using a pulse-echo method. The measurements were made both in vacuum-dry and fully saturated conditions in oolitic limestones of the Great Oolite Formation of southern England. Some of the rocks were fully saturated with oil. The acoustic measurements were supplemented by porosity and permeability measurements, petrological and pore geometry studies of resin-impregnated polished thin sections, X-ray diffraction analyses and scanning electron microscope studies to investigate submicroscopic textures and micropores. It is shown that the compressional- and shear-wave velocities (V-p and V-s, respectively) decrease with increasing porosity and that V-p decreases approximately twice as fast as V-s. The systematic differences in pore structures (e.g. the aspect ratio) of the limestones produce large residuals in the velocity versus porosity relationship. It is demonstrated that the velocity versus porosity relationship can be improved by removing the pore-structure-dependent variations from the residuals. The introduction of water into the pore space decreases the shear moduli of the rocks by about 2 GPa, suggesting that there exists a fluid/matrix interaction at grain contacts, which reduces the rigidity. The predicted Biot-Gassmann velocity values are greater than the measured velocity values due to the rock-fluid interaction. This is not accounted for in the Biot-Gassmann velocity models and velocity dispersion due to a local flow mechanism. The velocities predicted by the Raymer and time-average relationships overestimated the measured velocities even more than the Biot model.