Search

Building Energy Simulation (BES) tools play a key role in the optimization of the building system during the different phases, from pre-design through commissioning to operation. BES tools are increasingly used in research as well as in companies. New BES tools and updated versions are continuously being released. Each tool follows an independent validation process but rarely all the tools are compared against each other using a common case study. In this work, the modelling approaches of widespread dynamic simulation tools (i.e. EnergyPlus, TRNSYS, Simulink libraries CarnotUIBK and ALMABuild, IDA ICE, Modelica/Dymola and DALEC), as well as PHPP (a well-known quasi-steady-state tool), are described and the results of all the tools modelling the same characteristic office cell, defined within the IEA SHC Task 56, are compared on a monthly and hourly basis for the climates of Stockholm, Stuttgart and Rome. Unfortunately, different tools require different levels of input detail, which are often not matching with available data, hence the parametrization process highly influences the quality of the simulation results. In the current study to evaluate the deviation between the tools, frequently used statistical indices and normalization methods are analysed and the problems related to their application, in a cross-comparison of different tools, are investigated. In this regard, the deviation thresholds indicated by ASHRAE Guideline 14-2014 are used as a basis to identify results that suggest an acceptable level of disagreement between the predictions of a particular model and the outcomes of all models. The process of reaching a good agreement between all tools required several iterations and great effort on behalf of the modellers. To aid the definition of building component descriptions and future references for inter-model comparison a short history of the executed steps is presented in this work. Together with the comparison of the results of the tools, their computational cost is evaluated and an overview of the modelling approaches supported by the different tools for this case study is provided aiming to support the users in choosing a fit-for-purpose simulation tool.

The data presented in this article are the results of widespread building simulation tools (i.e. EnergyPlus, TRNSYS, Simulink/CarnotUIBK, Simulink/ALMABuild, IDA ICE, Modelica/Dymola and DALEC) used to simulate a characteristic office cell, described within IEA SHC Task 56 [1] , located in Stockholm, Stuttgart and Rome. Hourly data for each component of the thermal balance (i.e. Heating, cooling, infiltration, ventilation, internal gains, solar gains) and the hourly convective and radiative temperatures are reported for all the tools along with the ambient temperature and solar irradiation on the south facade. The mainly used statistical indices (i.e. Mean Bias Error, Mean Absolute Error, Root Mean Square Error and coefficient of determination) are applied to evaluate the accuracy of the tools. For more insight and interpretation of the results, please see “Detailed Cross Comparison of Building Energy Simulation Tools Results using a reference office building as a case study” [2] . This data set and evaluation methods are made available to ease the cross-validation process for other researchers.

By 2021, all new buildings in the European Union must be nearly zero-energy buildings in order to contribute to the achievement of the EU-CO2 neutrality by 2050. As the technical options to achieve highly-efficient building envelopes are available and well-known, there is no doubt that the most promising Heating Ventilation and Air Conditioning systems will include heat pumps and photovoltaic panels. However, there exist ongoing discussions on the optimal system layout and the integration of storage to achieve nZEB. In particular, there are some good arguments in favour of very low demand, while contrariwise also high flexibility is seen as an important feature to enable so-called grid-reactive operation of the building stock. Integration of onsite storage and its influence on the energy demand of the buildings and the corresponding electric load profile with focus on peak power is investigated.

Introduction Le desencombrement bronchique est un element cle de la kinesitherapie respiratoire chez les patients atteints de mucoviscidose afin de prevenir les recidives d’exacerbation pulmonaire et le declin de la fonction respiratoire. La diminution de la capacite inspiratoire (CI) est un indicateur approprie de la distension statique dans la mucoviscidose, et peut reveler une deterioration subclinique de la fonction respiratoire [1] . Cette etude multicentrique visait a evaluer les effets d’une nouvelle technologie de desencombrement sur la CI au repos chez des patients atteints de mucoviscidose cliniquement stables. Methodes Vingt et un patients mucoviscidose adultes inclus consecutivement dans 2 centres ont recu au cours d’une seance de kinesitherapie respiratoire prophylactique, une session de drainage bronchique de 20 min environ avec le dispositif Simeox (Physio-Assist, France). Les patients ont effectue sous la supervision d’un kinesitherapeute, 3 mesures valides de CI au repos (coefficient de variation moyen Resultats Population : 10 hommes (26,7 ± 6,3 ans) et 11 femmes (26,9 ± 8,1 ans). Apres la session de drainage, la CI etait augmentee significativement de 110 ± 140 mL et de 4 ± 5 % pred. (p Fig. 1 : correlation negative entre le % relatif de variation de CI et la CI% pred., p Conclusion La capacite inspiratoire au repos a ete amelioree apres une seule seance de drainage avec la technologie Simeox suggerant un effet direct sur la reduction de la distension pulmonaire statique. Ce mecanisme physiologique pourrait avoir un impact significatif sur l’evolution de la fonction pulmonaire dans la mucoviscidose et necessite d’etre confirme par des donnees a plus long terme.

The course in this book is intended for Licensed Practical Nurses, Registered Rurses (RN) and Advanced Practice Registered Nurses (APRN) working on a stroke unit in a skilled nursing facility and/or rehabilitation center. We used a competence profile to clarify what the level of education is and what is expected during and after the course, so that the results of the education can also be guaranteed in practice. The competence profile is based on the model ‘Miller’s Pyramid’ which is briefly described in this chapter. We discuss the core competences of nurses using the terms: “Knows”, “Knows how”, “Shows how” and “Does”. The top level of the pyramid concerns independent acting in complex situations. This requires an integrated whole of knowledge, skills, attitude and personal qualities. A student who works well at the level ‘Does’ can be considered competent. The stroke rehabilitation course for nurses concludes with a final assignment. This consists of writing a paper and presenting the findings to the group. In this chapter the criteria for the paper are described.

In order to continue with a systematic study that include different polymers and monomers, the residual active sites produced by heavy ion beams, that remain after the etching process, were used to start the grafting process. To produce tracks, foils of polypropylene (PP) were irradiated with 208 Pb of 25.62 MeV/n. Then, these were etched and grafted with acrylic acid (AA) monomers. Experimental curves of grafting yield as a function of grafting time with the etching time as a parameter were measured. Also, the grating yield as a function of the fluence and etching time was obtained. In addition, the permeation of solutions, with different pH, through PP grafted foils was measured.

The flow injection (FI) analytical determination of Se(IV) with 2,3-diaminonaphthalene (DAN) was assayed employing enhanced fluorometric detection. The different variables affecting the reaction rate between Se(IV) and DAN were studied in batch mode, and the best conditions for the 4,5-benzopiazselenol (Se–DAN complex) formation were found. On this basis, two different FI manifolds able to give optimal sensitivity were designed. Once established the optimal flow conditions for the product formation, a submicellar medium of sodium dodecylsulphate with the addition of beta-cyclodextrin was tested to perform enhanced fluorometric detection. A limit of detection of 0.3 ug l-1 of Se(IV), a linear dynamic range ranging between 1 and 500 ug l-1 of Se(IV) and a sampling throughput of 40 samples h-1 were obtained. A full discussion on each stage of the optimisation procedure and the validation of the propose methodology is provided. Fil: Pedro, Juana. Universidad Nacional del Litoral. Facultad de Ingeniería Química; Argentina Fil: Andrade, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Magni, Diana. Universidad Nacional del Litoral. Facultad de Ingeniería Química; Argentina Fil: Tudino, Mabel Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Bonivardi, Adrian Lionel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina

Many studies discuss the economic and technical aspects of flood warnings. Less attention has been given to the social and psychological patterns that affect alert services. In particular, the literature focuses on warnings activated in river basins or marine environments without providing clear evidence of relevance to Mediterranean coastal areas, even though these are subjected to growing flood risk related to climate change. This paper is a first attempt to bridge this gap. Our research develops an in- depth analysis of the village of Cesenatico on the Adriatic Sea coast. Here the municipality adopted two complementary warning systems: a siren and an alert via Short Message Service (SMS). The analysis focuses on a survey conducted in 2011 and 2012 with 228 participants. The relationships between social and behavioural variables and warning services are investigated, and so are flood preparedness and information dissemination. Qualitative evidence from informal interviews is used to support the understanding of key responses. The conclusions show how different social and behavioural patterns can influence the effectiveness and use of warning systems, regardless of the technology adopted and the structural mitigation measures implemented. Education, training and accountability are seen to be critical elements for improvement. Finally, the statistical output is used to suggest new questions and new directions for research.

An artificial neural network (ANN) procedure was used in the development of a catalytic spectrophotometric method for the determination of Cu(II) and Ni(II) employing a stopped-flow injection system. The method is based on the catalytic action of these ions on the reduction of resazurin by sulfide. ANNs trained by back-propagation of errors allowed us to model the systems in a concentration range of 0.5–6 and 1–15 mg l-1 for Cu(II) and Ni(II), respectively, with a low relative error of prediction (REP) for each cation: REPCu(II) = 0.85% and REPNi(II) = 0.79%. The standard deviations of the repeatability (sr) and of the within-laboratory reproducibility (sw) were measured using standard solutions of Cu(II) and Ni(II) equal to 2.75 and 3.5 mg l-1, respectively: sr[Cu(II)] = 0.039 mg l-1, sr[Ni(II)] = 0.044 mg l-1, sw[Ni(II)] = 0.045 mg l-1 and sw[Ni(II)] = 0.050 mg l-1. The ANNs-kinetic method has been applied to the determination of Cu(II) and Ni(II) in electroplating solutions and provided satisfactory results as compared with flame atomic absorption spectrophotometry method. The effect of resazurin, NaOH and Na2S concentrations and the reaction temperature on the analytical sensitivity is discussed. Fil: Magni, Diana. Universidad Nacional del Litoral; Argentina Fil: Olivieri, Alejandro Cesar. Universidad Nacional de Rosario; Argentina Fil: Bonivardi, Adrian Lionel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Primary percutaneous coronary intervention (PCI) has become an alternative to thrombolytic therapy as a reperfusion strategy for ST-elevation acute myocardial infarction (AMI).The main goal of this study was to determine whether PCI and thrombolytic therapy achieve comparable reperfusion rates, as evidenced by ST-segment resolution. Secondary end points included infarct vessel patency rates before hospital discharge and short- and long-term outcomes. Patients with ischemic chest pain with durationor =12 hours and no contraindication for thrombolytic therapy were included.Between October 1993 and August 1995, 58 patients were randomly assigned to streptokinase (SK) and 54 patients to primary PCI. Baseline clinical characteristics and infarct location were well balanced in both groups. Median age (interquartile range) was 68 (58, 75) years, 29% were women, and 78% of the patients met at least one criterion for "not low risk" AMI (anterior location, age70 years old, previous MI, systolic blood pressure100 mm Hg, and/or heart rate100 bpm). The median time from symptom onset to random assignment was 217 (139, 335) minutes in the PCI group and 210 (145, 334) minutes in the SK group. Median random assignment to balloon time was 82 (55, 100) minutes, and median random assignment to needle time was 15 (10, 26) minutes (P.0001). TIMI grade 3 flow after primary PCI was obtained in 85% of patients. The proportion of patients with ST-segment resolutionor =50% at 120 minutes was 80% in the PCI group and 50% in the SK group (P =.001). The predischarge angiogram showed the presence of TIMI 3 flow in 96% of patients who received PCI and 65% of patients who received SK (P.001). A composite of in-hospital death, reinfarction, severe heart failure, stroke, and major bleeding occurred in 15% of patients who received PCI and 21% of patients who received SK (P =.4). At 3 years, freedom from the composite end point of AMI, postdischarge revascularization, and death was 61% in the PCI group and 40% in the SK group (P =.025).Our study shows that primary PCI, as compared with SK, is associated with more effective ST-segment resolution, higher patency rates in the infarct vessel at 7 days, and more favorable clinical outcomes at 3 years of follow-up.

The authors describe the Mozart-mixed mode (MM) simulation system which was formed by a tight coupling of the Mozart multi-level simulator and the Eldo analog simulator. Mozart-MM spans all the digital levels from behavioral to pseudo-electrical as well as the analog circuit and behavioral levels. This work required the development of a new algorithm to couple a digital simulator with discrete time together with a circuit simulator with adaptable time step. The full Mozart interactivity has been extended to Mozart-MM allowing the user to have direct control of the simulation experiment, including the possibility to conditionally execute commands. New techniques for netlisting, X handling and for the verification of the interface unidirectionally assumption are also presented. The tool has been tested extensively and the results presented demonstrate its performance. >

OBJECTIVES AND DESIGN Angiotensinogen (AGT) gene variants influence angiotensinogen plasma levels in children and young adults. The angiotensinogen promoter (-6)A variant facilitates gene transcription in human tissues and it has been associated with high blood pressure in older adults. A young adult population can be used as a model to study genotype/phenotype associations between AGT (-6) variants and cardiovascular variables. METHODS AND RESULTS Anthropometric measurements, blood pressure and heart rate were taken in 422 white Caucasian students (mean age 23.5 years, SD 2.5 years). Family history for hypertension, physical activity and smoking history were evaluated. Left ventricular variables were measured by echocardiography. Carotid artery wall intimal-media thickness (IMT) was measured by high resolution sonography and digitalized morphometry. The AGT G(-6)A alleles were evaluated by mutagenically separated polymerase chain reaction controlled by direct sequencing. No significant associations were found between angiotensinogen genotype and blood pressure, cardiac variables [except for deceleration time in females which increased with the number of (-6)A alleles] and IMT. Allele frequencies were similar between the first and third tertile of blood pressure and left ventricular mass, and were also similar between negative or positive family history for hypertension (the last group having significantly higher systolic blood pressure in males, P = 0.04 and diastolic blood pressure in females, P < 0.01). Moreover, no relevant interaction on the cardiovascular variables was found between AGT genotype and body mass index. CONCLUSIONS The angiotensinogen G(-6)A variants do not affect cardiovascular parameters in young adults, but an effect of this polymorphism on cardiovascular phenotype (and hypertension) in older adults cannot be excluded. Additional factors, associated with ageing, should be present to unleash the supposed unfavourable potential of the (-6)A angiotensinogen variant.

In an effort to improve results in patients with relapsed or refractory Hodgkin's disease (HD), an intensive regimen combining vinorelbine (25 mg/m2 i.v. days 1 and 5) and high-doses of ifosfamide (3000 mg/m2/d, days 1-4 by continuous infusion) with mesna uroprotection and G-CSF support was designed. Forty-seven patients were treated; 14 had failure to initial induction therapy and 33 had disease relapsed from an initial response. The response rate was 83%, with 21 complete (45%, CR) and 18 partial remissions (38%, PR). Partial response was achieved after a median of two cycles (range 1-3) and CR after a median of six cycles (range 2-10). At the end of ifosfamide and vinorelbine, 10 patients in CR, one in PR, and one with stable disease also received radiotherapy to nodal sites of relapse. Eleven patients who had undergone peripheral blood stem cell (PBSC) harvesting following ifosfamide-vinorelbine proceeded to receive high-dose chemotherapy (HDCT) and PBSC transplantation. The main toxic effect was grade III-IV neutropenia, documented in 65% of cycles with a median duration of 4 days, and non-haematological toxicity was mild. The combination of high-doses of ifosfamide and vinorelbine was well tolerated and an active regimen in treatment of patients with relapsed and refractory HD. It was not only useful as salvage therapy with or without consolidative radiotherapy but it also was a valuable induction regimen before high-dose intensification therapy followed by PBSC reinfusion in patients eligible for this approach.

Twenty patients of both sexes, hospitalized because they were suffering from acute cardiorespiratory syndromes, have been studied in a clinical blind test on unbalanced groups of patients. This research aims to evaluate the therapeutic efficiency and intravenous tolerance of doxophylline. Patients were observed for 24 hours. Signs and symptoms were recorded on a semi-quantitative scale, and the clinical situation, haemogasanalysis, blood pressure, cardiac frequency, and other analytic controls were performed in order to verify the systemic tolerability. We can conclude, in agreement with the literature, that the group treated with doxophylline showed a better reduction in cardiac frequency, while maintaining the same effects on the respiratory apparatus.

Recent data suggest that contractile reserve in dysfunctional but viable myocardium during low-dose dobutamine infusion might be elicited not only by a direct inotropic stimulation but also by an increase in coronary blood flow. Aim of the study was to evaluate the effects of low-dose dobutamine on myocardial perfusion and function in asynergic but viable myocardium.Nineteen patients with coronary artery disease and severe regional dysfunction were studied. Both regional ventricular function and myocardial perfusion were assessed at rest (PRE), during low-dose dobutamine (DOB) and, in twelve patients, after revascularization (POST). Regional ventricular function was evaluated with two-dimensional echocardiography using a score index ranging from 1 to 4. Myocardial perfusion was studied using Tc-99m-sestamibi Single Photon Emission Tomography (SPET); uptake defects were graded from 0 (normal) to 4 (absent uptake). For both evaluations the left ventricle was divided in 16 segments and two vascular territories were considered.Low-dose dobutamine elicited contractile reserve in 12 of 24 asynergic vascular territories (DOB+). Compared with PRE scintigraphy, DOB SPET showed perfusion improvement in 10/12 DOB+ and in 3/12 DOB- asynergic territories (p = 0.006). Mean uptake score decrease significantly in DOB+ (from PRE SPET 21.0 +/- 7.2 to DOB SPET 17.6 +/- 7.1; p = 0.0005) but not in DOB- (from SPET PRE 19.0 +/- 5.3 to SPET DOB 19.5 +/- 6.8, p = NS) abnormal territories. Fourteen asynergic territories underwent revascularization. Among them, 9 showed functional recovery after intervention (viable myocardium) and 5 showed no changes (fibrotic myocardium). A functional improvement under dobutamine was observed in 7 viable and in 1 fibrotic territories. Conversely, perfusion improved under dobutamine in 8 viable and in one fibrotic territory. After revascularization the perfusion defect score decreased significantly in viable territories (from PRE SPET 22.1 +/- 7.9 to POST SPET 13.3 +/- 6.6; p = 0.00001) but not in fibrotic regions (from PRE SPET 17.8 +/- 6.0 to POST SPET 15.6 +/- 4.9).In asynergic myocardium contractile reserve elicited by low-dose dobutamine is associated in most cases with an improvement in Tc-99m-sestamibi uptake. This suggests a possible link between increased blood flow and functional improvement during dobutamine in viable myocardium.

The identification of genes inducing resistance to anticancer chemotherapeutic agents and their introduction into hematopoietic cells represents a promising approach to overcome bone marrow toxicity, the limiting factor for most high-dose chemotherapy regimens. Because resistance to cyclophosphamide has been correlated with increased levels of expression of the aldehyde-dehydrogenase (ALDH1) gene in tumor cell lines in vitro, we tested whether ALDH1 overexpression could directly induce cyclophosphamide resistance. We have cloned a full-length human ALDH1 cDNA and used retroviral vectors to transduce it into human (U937) and murine (L1210) hematopoietic cell lines that were then tested for resistance to maphosphamide, an active analogue of cyclophosphamide. Overexpression of the ALDH1 gene resulted in a significant increases in cyclophosphamide resistance in transduced L1210 and U937 cells (50% inhibition concentration [IC50], approximately 13 mumol/L). The resistant phenotype was specifically caused by ALDH1 overexpression as shown by its reversion by disulfiram, a specific ALDH1 inhibitor. ALDH1 transduction into peripheral blood human hematopoietic progenitor cells also led to significant increases (4- to 10-fold; IC50, approximately 3 to 4 mumol/L) in cyclophosphamide resistance in an in vitro colony-forming assay. These findings indicate that ALDH1 overexpression is sufficient to induce cyclophosphamide resistance in vitro and provide a basis for testing the efficacy of ALDH1 gene transduction to protect bone marrow cells from high-dose cyclophosphamide in vivo.

Mitral valve prolapse (MVP) is generally regarded as a benign condition, but serious complications (including severe mitral insufficiency, cerebral ischemia, infective endocarditis, complex arrhythmias and sudden death) have been described in a minority of patients and have been correlated to demographic, clinical and echocardiographic characteristics. Both a lack of standardized definition of MVP in earlier studies and the different ways of recruitment of MVP patients may explain the variability in reported complication rates.As an offspring of a larger prospective study this paper focuses on the profile of patients who were found to have MVP by M-Mode and two-dimensional echocardiography in several outpatient hospital departments. A total of 8252 consecutive subjects, examined since March 1990 to February 1991 in the Echo laboratories of the Florence area are considered; according to the presence or absence of structural changes (anterior mitral leaflet thickness5 mm, leaflet redundancy and/or anulus dilatation) two groups of patients with MVP (A and B) were identified.A MVP was diagnosed in 288 subjects (3.5%), 170 females (59%) and 118 males (41%), mean age 41 +/- 18 years (range 7-84). 110 (38%) were in Group A, 178 (62%) in Group B. The following parameters differed significantly in the two groups: age (45 +/- 17 vs 39 +/- 17 years; p0.003); male gender (50% vs 35%; p0.01); auscultatory findings (midsystolic click: 31% vs 68%; p0.00001; holosystolic murmur: 22% vs 3%; p0.00001); left ventricular diameter (53 +/- 7 vs 48 +/- 5 mm; p0.00001) and left atrial diameter (38 +/- 8 vs 33 +/- 5 mm; p0.00001). Among patients with mitral regurgitation detected by Color Doppler Echocardiography 65% were in Group A (p0.00001).These patients with MVP are obviously selected by the modality of recruitment; hence there is a higher prevalence of subjects with morphologic abnormalities and mitral regurgitation who are older and more likely to be male if compared to individuals with MVP who are found in the general population. A long-term follow-up of these patients is ongoing: owing to the data of the literature about prognostic predictors, a higher incidence of complications with a different prognosis between the two groups (with or without structural changes of the mitral valve) is expected.

The authors describe the case of an epileptic patient in chronic therapy with carbamazepine, and with plasma concentration of the drug in therapeutical range, who suffers from persistent sinus tachycardia. At the present time the observations available in the literature on cardiac toxicity of carbamazepina concern the appearance of sinus tachycardia as consequence of overdose and of blocks of conduction in elderly with carbamazepine in therapeutical range.

With the aim of facilitating the ex vivo manipulation of peripheral blood hematopoietic progenitors (CPCs = circulating progenitor cells) collected by leukapheresis, we removed polymorphonuclear cells and monocytes that naturally adhere to nylon wool fibers. Leukapheresed cells harvested at the time of hematopoietic recovery after cancer therapy with high-dose cyclophosphamide plus hematopoietic growth factors were incubated with nylon wool fibers for 1 h at 37 degrees C. Evaluation of the cells non-adherent to the nylon wool in all experiments (n = 14) showed that the median recovery of nucleated cells and CPCs detected as CD34+ cells, CFU-GM and BFU-E was 16.4% (range 4.8%-34.0%), 60.0% (range 30.8-80.8%), 60.9% (range 33.4-74.5%) and 65.5% (range 30.8-69.2%), respectively. Therefore exposure to the nylon wool determined a selective removal of mature cells and a complementary enrichment of CPCs. The wide range of results depended on the significantly different cell compositions of the unmanipulated leukaphereses. The latter from patients receiving rhG-CSF (n = 10) comprised a median of 88.5% (range 77.8-93.8%) and 11.5% (range 6.2-22.2%) polymorphonuclear and mononuclear cells, respectively. In contrast, leukaphereses from patients receiving rhGM-CSF or PIXY321 (n = 4) comprised a median of 71.1% (range 55.4-85.0%) and 28.9% (range 15.0-44.6%) polymorphonuclear and mononuclear cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

After myeloablative regimens, combined reinfusion of peripheral blood hematopoietic circulating progenitor cells (CPC) and bone marrow, yields a very rapid hematopoietic recovery. Therefore, based on the knowledge that CPC express the CD34 and CD33 differentiation antigen, we have developed a direct immunofluorescence flow cytometry assay to detect the peak of CPC in the peripheral blood of patients treated with high dose chemotherapy and growth factors. This assay, compared to CFU-GM assay, has the following advantages: 1) easy to do 2) standardized method 3) real time information on CPC number. This work illustrates the practical aspects of this assay and substantiate the widespread use of the CD34/33 flow cytometry assay to guide harvesting of circulating hematopoietic progenitors for autologous transplantation.

The existence of a direct link between receptor-activated phospholipid hydrolysis and changes of cellular Ca2+ homeostasis was hypothesized quite some time ago but remained unclear, being based largely on anecdotal evidence, until the discovery almost a decade ago of the specific Ca2+ release activity of inositol 1,4,5-trisphosphate (IP3) (reviewed by Berridge and Irvine, 1989). Initially, the reaction responsible for IP3 generation, i.e., the hydrolysis of phosphatidyl inositol 4,5-bisphosphate (PIP2) by specific phospholipase(s) C (PLC), was thought to be the only metabolic process by which [Ca2+]i was regulated. However, the field soon became more complex. In 1984–85, activation of the receptors coupled to PPI hydrolysis was shown to stimulate not only Ca2+ release from internal stores but also Ca2+ influx via channels in the plasmalemma, later named second messenger-operated channels (Meldolesi and Pozzan, 1987). The multiplicity and complex regulation (not only by second messengers, but also via G proteins and the physiological state of intracellular Ca2+ stores) of these channels is discussed elsewhere (Meldolesi et al., 1991).

Hematopoietic progenitor cells circulate in the peripheral blood (PB) of cancer patients during the recovery phase that follows treatment with high-dose cyclophosphamide followed by hematopoietic growth factor infusion. We report that when PB progenitors were exposed in vitro to filtered supernatant from cell line PA317-N2, producing amphotropic helper-free N2 vector at conventional titers, successful retroviral-mediated transfer of neomycin resistance gene was documented by polymerase chain reaction in 93% of day 14 myelomonocytic colonies. Under the same conditions, gene transfer was achieved in 22% of steady-state bone marrow-derived myelomonocytic colonies. Neo-resistance gene transfer was documented also in a CD34+/cyclophosphamide-resistant precursor to granulocyte-macrophage colonies, an undifferentiated progenitor close to the hematopoietic stem cell. Neither cocultivation with vector-producing cells nor high vector titer were stringent requisites for efficient gene transfer. The large-scale availability of PB hematopoietic progenitors in cancer patients, together with the high gene transfer rate achieved under safe and clinically feasible conditions, support an optimal approach for gene transfer procedures into the human hematopoietic system.

The effects of epidermal growth factor (EGF) on membrane potential were investigated in suspensions of the following three cell types endowed with a large complement of specific receptors: EGFR-T17 (a clone of mouse NIH-3T3 fibroblasts overexpressing EGF receptors); A431 and KB (two human carcinoma lines). In all these lines EGF induced a rapid and marked hyperpolarization constituted by an initial peak (in all three cell lines) and a subsequent sustained plateau phase, concomitant with the well-known increase of [Ca2+]i. The time course and phorbol ester inhibitability of the membrane potential effects were the same as for the [Ca2+]i response. Experiments with Na+-free and chloride-free media excluded a major role of the latter ions in the EGF-induced hyperpolarization. In contrast, experiments with high K+ media, with the monovalent cation ionophore gramicidin and with Ca2+-free media together with either a Ca2+ ionophore (ionomycin, in A431 and EGFR-T17), or an agonist (bradykinin, in A431) addressed to a receptor coupled to phosphoinositide hydrolysis, were consistent with the involvement of Ca2+-activated K+ channels. The EGF-induced hyperpolarization was completely blocked by the K+ channel blocker, quinidine, and unaffected by a variety of other drugs. Patch clamping of individual EGFR-T17 cells confirmed the initial hyperpolarization (from approximately -30 mV, the resting potential, to -60, -80 mV) was due to activation of an outward current. This initial hyperpolarization was followed by fluctuations (period approximately 1 min) persisting as long as the cells could be analyzed. Thus, the changes of membrane potential appear to be not only novel members of the group of early events triggered by EGF in target cells but also long-lasting effects of the growth factor, which continue for unexpectedly long periods of time after EGF application.

Two clones of NIH3T3 fibroblasts, NEN37 and NEN7, overexpressing chimeric EGF/neu receptors (3 x 10(5) and 1 x 10(6) receptors/cell, respectively), were treated with EGF in order to identify the array of intracellular signals generated after activation of the neu proto-oncogene product. The results thus obtained were correlated with the effects of EGF on cell growth, investigated by both [3H]thymidine incorporation and long term (5 days) proliferation studies. In addition to the stimulation of the neu tyrosine kinase, previously reported by Lehvaslaiho et al. (EMBO J., 8, 159-166, 1989), EGF (10(-9)-10(-8) M) was found to induce marked increases of both [Ca2+]i and plasma membrane potential (investigated by the fura-2 and bis-oxonol techniques) which, in their initial phase, were only marginally dependent on the presence of Ca2+ in the incubation medium. These responses were inhibited, but only in part (40-50%) by phorbol ester activators of protein kinase C. Moreover, inositolphosphate analysis (by anion exchange chromatography) revealed hydrolysis of membrane polyphosphoinositides. All these effects of EGF were more prompt and much larger in NEN7 than NEN37 cells. The EGF concentration-dependence curves (measured by both [3H]thymidine incorporation and long-term proliferation assay) were quite different in the two cell clones. In the cells expressing the lower number of receptors measurable growth stimulation was observed at 10(-10), and maximal effect at 10(-9) M EGF. In NEN7 cells the curve was much more shallow, with measurable stimulation already at 10(-12) and maximal effect at 10(-8) M EGF. The maximal growth effect was approximately the same for the two cell clones. It is concluded that the intracellular signals identified here may play a limited role in the neu-induced cell proliferation, but are possibly involved in the acquisition of the tumoral phenotype typically expressed by the EGF-treated NEN7 cells.

An indoor hot spot test procedure for photovoltaic modules is described.Test procedures for different cell interconnection circuits, from simple series connected strings to more complex series-parallel configurations, are suggested. Results from tests on nearly sixty module types are presented. Scanning electron microscopy and infrared imaging have been used to identify the basic phenomena giving rise to hot spots. Local heating has been correlated with the presence of surface defects.

Solar Envelope systems, which represent the technological response for meeting aesthetic requirements and solar renewable energy exploitation on building facades, are gaining rising attention. However, they are still rare on the market. IEA SHC Task 56 focuses on the critical analysis, simulation, laboratory tests and onsite monitoring of market available and near market Solar Envelope systems. Within this framework, reference boundary conditions are required in order to assess the performance of Solar Envelope systems and compare different technologies through numerical simulations. The present paper reviews the process of defining reference boundary conditions for an office building, listing possible simplifications and required assumptions in order to calculate the impact at whole building level in terms of useful and final energy savings related to the installation of a facade integrated technology. The paper concludes with a comparison of simulation results between TRNSYS and DALEC, a simplified concept evaluation tool, which performs combined thermal and lighting analysis already at early design stages.

The identification of genes inducing resistance to anticancer chemotherapeutic agents and their introduction into hematopoietic cells represents a promising approach to overcome bone marrow toxicity, the limiting factor for most high-dose chemotherapy regimens. Because resistance to cyclophosphamide has been correlated with increased levels of expression of the aldehyde-dehydrogenase (ALDH1) gene in tumor cell lines in vitro, we tested whether ALDH1 overexpression could directly induce cyclophosphamide resistance. We have cloned a full- length human ALDH1 cDNA and used retroviral vectors to transduce it into human (U937) and murine (L1210) hematopoietic cell lines that were then tested for resistance to maphosphamide, an active analogue of cyclophosphamide. Overexpression of the ALDH1 gene resulted in a significant increases in cyclophosphamide resistance in transduced L1210 and U937 cells (50% inhibition concentration [IC50], approximately 13 mumol/L). The resistant phenotype was specifically caused by ALDH1 overexpression as shown by its reversion by disulfiram, a specific ALDH1 inhibitor. ALDH1 transduction into peripheral blood human hematopoietic progenitor cells also led to significant increases (4- to 10-fold; IC50, approximately 3 to 4 mumol/L) in cyclophosphamide resistance in an in vitro colony-forming assay. These findings indicate that ALDH1 overexpression is sufficient to induce cyclophosphamide resistance in vitro and provide a basis for testing the efficacy of ALDH1 gene transduction to protect bone marrow cells from high-dose cyclophosphamide in vivo.

This paper aims to explore what the factors enabling or threatening IT and IS innovation choices are and how they interact to mould organisational change in professional service firms, and especially in accounting firms. We employ a survey carried out in the Italian setting, relating to IT and IS strategies to understand whether they may enable innovation and knowledge creation and sharing. The paper reveals complex and multifaceted circumstances, providing interesting implications both under academic and managerial aspects.