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The interaction between plasma sex hormone-binding globulin (SHBG) and its receptor (SHBG-R) inhibits estradiol-induced proliferation of MCF-7 cells (human estrogen-dependent breast cancer) through cAMP and PKA. Thus, SHBG can modulate estradiol action in breast cancer, but the implications of this require a more detailed knowledge of the SHBG-R. To this end, we have transfected MCF-7 cells with an expression vector carrying the human SHBG cDNA (S-MCF-7) and studied the effects of this on both SHBG-R binding and cell proliferation. Control cells were parental MCF-7 (P-MCF-7) and MCF-7 cells transfected with the β-galactosidase gene (B-MCF-7). Transfections were mediated by lipofectin followed by selection of transfected cells with G418. The amounts of SHBG in culture medium were evaluated by IRMA assay, with only S-MCF-7 cells shown to secrete SHBG; SHBG-R levels were evaluated by tracer binding technique. In P-MCF-7 and B-MCF-7 cells, SHBG-R was detectable as a two-binding site receptor, but no binding of SHBG was observed in S-MCF-7 cells. Proliferation of cells treated with estradiol was evaluated by [ 3 H]thymidine incorporation in the three cell lines and in cells pretreated with SHBG (1 nM) purified from human serum or with conditioned medium from S-MCF-7 cells (medium S). In all three lines, cell proliferation increased after estradiol treatment. Preincubation with purified SHBG was effective in reducing estrogen-induced cell proliferation to basal levels in P-MCF-7 and B-MCF-7 but not in S-MCF-7 cells. The estradiol effect was also inhibited in P-MCF-7 cells treated with medium S. In conclusion, 1) SHBG inhibits estradiol-induced proliferation in cells containing a functional SHBG-R, whereas it has no detectable effect in cells in which the SHBG-R is either absent or not available to bind SHBG; and 2) S-MCF-7 cells are insensitive to SHBG (locally produced or exogenous) because their SHBG-R is occupied by SHBG.

The economic lot scheduling problem (ELSP) is a well known problem that focuses on scheduling the production of multiple items on a single machine such that inventory and setup costs are minimized. In this thesis the ELSP is extended to include price optimization with the objective to maximize profits. Two variants are proposed: a deterministic version which will be known as the PELSP and the stochastic version which is called the SPLSP. A solution methodology based on column generation and integer programming is proposed and is shown to produce very close to optimal results with short solution times. Computational testing is performed to evaluate the methodology. The results are discussed and recommendations for further research are provided. Maestro en Ciencias con Especialidad en Calidad y Productividad

Multiple embryo transfer is associated with a high frequency of twin pregnancies with costly complications involving both mother and child. As a result high priority is currently being given to the development of single embryo transfer (SET) programs. France seems to be lagging behind Northern European countries in the development of SET and widespread use of SET will depend on convincing physicians that this policy will not have a negative impact on success rate, as has been the case for many protocols described in the literature as well as in our own experience. Our SET program includes patients less than 36 years of age undergoing their first FIV-ICSI. If two embryos showing satisfactory morphology are obtained, one is selected transferred and the other is systematically frozen. Selection for transfer is based on two criteria, i.e. observation of even early cleavage 26 hours after FIV-ICSI and evaluation of embryo morphology score on day 2. Embryo morphology score is based on the presence of four blastomeres and absence of blastomere irregularities and anucleated fragmentation. Last, a prerequisite for SET is an effective freezing program. A pregnancy rate of 13% per thawing was sufficient enough to obtain a cumulative pregnancy rate after SET (N = 205) and subsequent frozen embryo transfer (FET) similar to the cumulative pregnancy rate obtained after double embryo transfer (N = 394) and subsequent FET (46.3 vs 46.7%, NS). Twin delivery rate were respectively 2,6% after SET and 26,6% after double embryo transfer (P0.01).

A pilot study was conducted to evaluate safety and activity of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in colorectal carcinoma (CRC) and to determine whether a T-cell response to a tumor-associated antigen (TAA) was induced. Fifteen patients with metastatic CRC underwent HCT from human leukocyte antigen (HLA)-matched siblings after a nonmyeloablative conditioning regimen. All patients engrafted with a median donor T-cell chimerism of 72% at day +56. Eight patients experienced grades II to IV acute graft-versus-host disease (GVHD). Despite progressive disease before HCT, partial remission and disease stabilization longer than 90 days were observed in 1 and 3 patients, respectively. Induction of TAA-specific T cells was evaluated with a carcinoembryonic antigen (CEA)-specific HLA-A(*)0201 pentamer in 6 patients with CRC. CEA-specific CD8(+) T cells were detected in 3 of 3 patients concomitant with GHVD onset, but not in 3 of 3 patients without GVHD. They were also not detected in 9 of 9 control patients with GVHD who received transplants for diagnoses other than CRC. Antitumor activity of CEA-specific T cells was also validated in vitro. In one patient, the induction of CEA-specific T cells was associated with a decrease of serum CEA levels and a partial response. Thus, graft-versus-host reactions associated with allogeneic HCT can trigger the generation of T cells specific for CEA, and this may be associated with a clinical response.

Polycyclic aromatic hydrocarbons (PAHs) are one of the main classes of contaminants in the terrestrial environment. Aside from total organic carbon, the ratio among the different organic matter fractions [dissolved organic matter, fulvic acid (FA), humic acid (HA) and humin] can also affect the mobility of these hydrocarbons in soils. In this study the effect of the whole organic carbon pool has been compared with that of HA and FA on the translocation of four PAHs (biphenyl, fluorene, phenanthrene and pyrene) in soil columns. Oxidized and untreated soil columns with and without HA or FA, were prepared, spilled with hydrocarbons and leached with a 0.01 M CaCl2 solution. The influence of HA and FA on PAH translocation was investigated through determinations of the PAH contents and total organic carbon (TOC) in the layers of the columns. All molecules were moved vertically by the percolating solutions, their concentrations decreasing with depths. The nonoxidized soil tended to retain more PAHs (96%) than the oxidized one (60%), confirming that organic matter plays an important role in controlling PAH leaching. The whole organic matter pool reduced the translocation of pollutants downward the profile. The addition of HA enhanced this behaviour by increasing the PAH retention in the top layers (7.55 mg and 4.00 mg in the top two layers, respectively) while FA increased their mobility (only 2.30 and 2.90 mg of PAHs were found in the top layers) and favoured leaching. In fact, in the presence of HA alone, the higher amounts of PAHs retained at the surface and the good correlation (r2=0.936) between TOC and hydrocarbon distribution can be attributed to a parallel distribution of PAHs and HA, while in the presence of FA, the higher mobility of PAHs can be attributed to the high mobility of the humic material, as expected by its extensive hydrophilic characteristics.

Background. The role of normal lymphocytes in the development of malignancies is investigated with increasing interest, with particular focus on lymphoproliferative disorders. A few recent reports, including a large study from our group, have shown that the lymphocyte/monocyte ratio (LMR) is often altered in diffuse large B cell lymphoma (DLB-CL) and a reduced LMR at diagnosis is associated with a poor response to therapy and a marked reduction in the overall survival expectancy. Reduction of LMR is primarily due to decreased levels of circulating lymphocytes, although an increase of circulating monocytes may also concur in reducing the LMR value. The present study was undertaken to further characterize the lymphocyte subpopulations in DLB-CL and in the other germinal-center derived Follicular Lymphoma (FL). In particular, the aim was to investigate possible abnormalities of either B or T-lymphocytes that might be present in patients with DLB-CL or FL at disease onset. Patients and Methods. Peripheral blood (PB) samples were obtained at diagnosis from 23 DLB-CL and 15 FL without leukemic involvement; among them 11/23 DLB-CL and 12/15 FL did not display disease involvement also in their bone marrow (BM). In addition, 25 PB and 20 BM were obtained as controls from age matched healthy donors or from subjects undergoing diagnostic procedures without any evidence of hematological or solid malignancy. Multicolor flow cytometry (MFC) was used, to evaluate the PB distribution and the absolute value of the main cell categories, i.e.: CD3+ T cell, CD3-CD56+ NK cells, and CD19+CD20+ B cells; among these latter, the following subsets were investigated: transitional (CD38+high/CD24+high/IgD+/CD27-), naive (CD38+/CD24+/IgD+/CD27-), memory IgD+ (CD38-/+CD24+/IgD+/ CD27+), and memory IgD- (CD38-/CD24+high/IgD-/CD27+). Similarly, MFC was used to identify B-lymphocyte subsets in BM samples (B cell precursors as CD19+CD20-CD10+ and mature B cells as CD19+CD20+CD10-). Results. The absolute number of circulating B cells was significantly reduced in both FL (median 86 cell/ul) and DLB-CL (median 72 cell/ul) compared to normal age-matched controls (median 233 cells/ul), as detailed in the Figure 1. The low absolute number of circulating B cells did not correlate with a low LMR or with bone marrow involvement. Despite the generalized reduction in absolute number, the proportion of transitional and naïve B cell subsets was similar or slightly increased in B-NHL, while the percentage of memory B cell was deeply reduced in both FL and DLB-CL compared to normal controls. The amount of BM CD19+ B cells, evaluated as percentage on the whole lymphocyte population, was similar in both FL and DLBCL (15% and 15.9% respectively) and not significantly different from normal controls (18.9%). Interestingly, the percentage of B cell precursors (CD19+CD20-CD10+) within the B cell compartment was similar in FL and normal BM (50% vs 43.1%, p=ns), while it was marginally reduced in DLB-CL (23.7% vs 43.1%, p=ns). T and NK cells were not significantly different in DLB-CL and FL and in normal controls. Conclusions. Our data suggest that the homeostasis of normal B-cell compartment is impaired in FL and DLBCL, mainly at the peripheral level. The circulating memory B cells seem to be the B-cell subset affected in FL and DLB-LC. The mechanism underlying the reduction of circulating B lymphocyte number remains unknown. It might be hypothesized that FL and DLB-CL affect the microenvironment in which normal B cell differentiation occurs, resulting in the hampered production or increased elimination of differentiating B-cells. This hypothesis seems supported by the observation that the B cell population is not significantly altered in BM. Further study should be addressed to verify the impact of B-cell reduction on the long-term outcome of DLB-CL e FL and whether increasing circulating B-cells may improve the response to therapy. In addition the results here reported should be considered in relation with the prolonged B-cell impairment associated with the widely employed chemo-immunotherapy treatments for B-cell lymphoma. Figure 1. Absolute count values of total PB B lymphocyte in normal control (dottet bar), DLBCL (vertical line bar) and FL (diagonal line bar). Figure 1. Absolute count values of total PB B lymphocyte in normal control (dottet bar), DLBCL (vertical line bar) and FL (diagonal line bar). Disclosures No relevant conflicts of interest to declare.

Introduction La gravite est une constante qui joue un role capital dans l’execution et la perception du mouvement humain. Sur Terre, les informations gravito-inertielles nourrissent l’ensemble des representations internes de l’action et du corps, sur lesquelles le SNC s’appuie pour controler et percevoir le mouvement. En microgravite, l’ensemble des informations graviceptives sont transitoirement supprimees ou perturbees. Afin de preciser les capacites du SNC a extraire les informations gravito-inertielles pertinentes contenues dans la cinematique d’un mouvement humain, nous avons mis au point un ensemble de stimuli enregistres en normo- et microgravite, modelises sous la forme de points lumineux. Materiel et methode Nous avons examine les reseaux cerebraux en charge de la perception visuelle du mouvement humain realise en normo- et microgravite, chez 20 jeunes adultes, naifs a la microgravite, lors d’une etude en imagerie par resonance magnetique fonctionnelle (IRMf). Resultats – discussion La perception du mouvement humain dans les deux conditions s’appuie sur un reseau cerebral identique impliquant des regions frontale, parietale et temporo-occipitale, caracteristiques de la perception des mouvements biologiques. En revanche, il existe des gradients d’activation au niveau de certaines regions motrices, qui appartiennent au systeme des neurones miroirs, en particulier le cortex moteur primaire, dont l’activation est plus importante dans la condition normogravite. Ainsi, la perception du mouvement humain, en normo comme en microgravite, s’effectue au travers d’un processus de resonance motrice dans lequel les mouvements observes sont simules par le sujet observateur sur la base de propre son repertoire moteur ; les 8-mouvements jamais executes en microgravite conduisant a une moindre activation de ses regions motrices.

Introduction Agir avec son environnement necessite d’etre conscient de son propre corps. Cette conscience corporelle est basee sur le schema corporel qui correspond a la representation interne du corps en action. La construction du schema corporel au cours de l’ontogenese repose grandement sur la proprioception. La maturation des bases cerebrales sous-jacentes a l’integration proprioceptive reste encore peu connue. C’est autour de 8 ans que l’integration d’informations proprioceptives au service du controle en ligne du mouvement devient plus operationnelle, signant une maturation progressive des afferences proprioceptives (Contreras-Vidal et al., 2006). De plus, une immaturite du reseau proprioceptif a ete observee chez les adolescents, qui se caracterise par une moindre differentiation en comparaison des adultes (Cignetti et al., 2014 ; Assaiante et al., 2014). Materiel et methode Vinght enfants de 8 a 10 ans, ont ete places dans un scanner IRMf. Des illusions de mouvement de flexion plantaire ont ete induites grâce a des vibrateurs. Les vibrations delivrees etaient soit de faible frequence (30 Hz), soit de plus haute frequence (100 Hz) pouvant provoquer une illusion de mouvement. Resultats – discussion Les analyses preliminaires des cartes d’activation et de connectivite fonctionnelle et structurelle suggerent une moindre maturite des regions fronto-parietales sous-jacentes a l’integration proprioceptive chez l’enfant, a l’inverse des regions sensorimotrices dont les proprietes sont comparables a celles de l’adulte. La construction du schema corporel, qui s’appuie sur ces regions associatives, est donc un processus qui mature lentement au cours de l’ontogenese.

Reducing the energy consumed in the use of mobile and wireless devices is becoming a major design challenge. While the problem obviously must be addressed with improved low-level technology, we have advocated also considering a higher-level view in which energy management becomes an explicit design goal of the software developer who can be more aware of the needs of applications. In support of this objective, new programming models, measurement tools, and simulation environments must be developed to provide the developer with feedback on the energy implications of various design decisions. In this paper, we describe an energy model and an execution-driven simulator incorporating this model for the PalmOS™ family of devices.

Adoptive immunotherapy of leukemia aims at eradicating the disease through the transfer of leukemia-reactive lymphocytes. Donor lymphocytes infusions (DLI) after allogeneic hemopoietic cell transplantation (allo-HCT) have shown to cure chronic myelogenous leukemia (CML). Unfortunately, when applied to acute leukemias, the DLI approach is far less successful. Strategies to increase the efficacy of adoptive immunotherapy for the cure of acute leukemias are therefore urgently needed. To this aim, blasts from acute myeloid leukemias (AML) can be differentiated in vitro into dendritic cells (leukemic DC or LDC) that directly present leukemic antigens to T lymphocytes. This is commonly achieved by culturing AML blasts with cytokines such as GM-CSF, IL-4 and TNF-α for 7–14 days. LDC can be further induced to functional maturation by exposure to CD40L. The efficacy of these protocols is, however, suboptimal, since a large proportion of AML sub-types do not differentiate into LDC. The addition of calcium ionophore (A23187) has been shown to rescue some of the cases. The aim of this study is to identify the characteristics associated with the ability of blast from AML to differentiate into functionally mature LDC. To this, we studied a cohort of 17 consecutive AML patients. AML blasts were induced to differentiate into LDC either by GM-CSF, IL-4 and TNF- α or by cytokines and A23187. LDC were further matured with CD40L. LDC differentiation was defined by expression of MHC class II, costimulatory (CD80, CD86, CD40, CD70) and adhesion molecules (CD54, CD58). The overall efficacy of LDC differentiation by cytokines was 20%. Maturation of LDC induced by cytokines failed, as ascertained by the lack of up-regulation of CD83 and the chemokine receptor CCR7. Upon exposure of AML blasts to cytokines and A23187, we observed LDC differentiation in more than 90% of the cases. LDC differentiation occurred in 24–48 hrs and was associated with the maintenance of disease markers expression (c-kit, CD34). Interestingly, blasts derived from AML secondary to myelodysplastic syndromes directly differentiated into mature LDC. On the other hand, LDC derived from primary AML were insensitive to the maturative stimulus CD40L. Accordingly, LDC from secondary AML were the most potent inducers of allogeneic T-cell proliferation. The efficacy of the combination of calcium ionophore and cytokines in differentiating myelodysplastic blasts into LDC provides the rational for novel adoptive immunotherapeutic approaches to treat high risk AML. Furthermore, the differential ability of primary leukemic blasts and blasts secondary to myelodysplastic syndromes to rapidly differentiate into functionally mature LDC suggest the existence of molecular factors committing AML cells to the DC lineage. The identification of such factors and their exploitation, for example by gene transfer, will enable the generation of LDC from all cases of AML for the stimulation of the immune system against leukemia.

INTRODUCTION Interferon-alpha (IFN) plays a role in the management of different neoplasias, particularly those of hematological origin. The mechanisms of action of IFN are still poorly understood and the individual response is unpredictable. In the present study, the pattern of intracellular gene expression following in vitro and in vivo exposure of chronic myeloid leukemia (CML) cells to IFN was evaluated and correlated with the response to in vivo treatment with IFN. MATERIALS AND METHODS CML patients in different phases of the disease were studied. The pattern of expression of two IFN-inducible proteins involved in IFN-mediated biological activities, the p91 and p84 proteins (STAT1alpha and STAT1beta), components of the IFN-stimulated gene factor 3 (ISGF3) complex and the enzyme 2'-5' oligoadenylate synthetase (2'-5' OASE) were investigated by Western blot in peripheral blood mononuclear cells stimulated or not in vitro by IFN. RESULTS AND CONCLUSIONS In 6/9 patients evaluated before starting treatment, STAT1 was expressed either constitutively or after in vitro stimulation by IFN. In three cases, STAT1 remained negative even after in vitro activation. The pattern of protein expression correlated with the subsequent hematological response to prolonged in vivo IFN administration: the presence of STAT1 being associated with the clinical response to IFN and the absence and non-inducibility of STAT1 with resistance to IFN. This was further substantiated by studies carried out in ten patients analyzed at the time of a documented clinico-hematological response or resistance to the in vivo administration of IFN. Finally, in order to establish whether the pattern of response to IFN treatment could be predicted at diagnosis, cells cyropreserved at diagnosis from patients with a documented complete response, confirmed also by cytogenetic negativity, or resistance, were studied. While complete responders proved STAT1 positive, none of the four resistant cases ever expressed STAT1. The expression of 2'-5' OASE did not correlate with the clinical response to IFN. This study documents the pivotal role of STAT1 in the in vitro and in vivo responses of CML cells to IFN. The constitutive or induced presence or absence of STAT1 shows a predictive correlation with the response or resistance to treatment with IFN and could be utilized to identify, at diagnosis, resistant patients who may be spared an expensive and unnecessary prolonged IFN administration.

The goal of these studies is to identify genes that are preferentially expressed in leukemias by using a combination of cDNA library subtraction and microarray analysis. A human leukemia cDNA library was constructed by subtracting a normal bone marrow library from a library derived from a pool of the most common AML FAB subtypes (M1, M2, M4, M5). Prescreening of the library showed enrichment of leukemia associated genes and a high complexity, as evidenced by the low frequency of repeated isolation of the same clones. For microarray analysis of the subtracted cDNA library, 2500 clones from the subtracted library were randomly picked, PCR amplified and arrayed onto glass slides as multiple replicates. To determine tissue distribution of the putative leukemia associated genes, the arrayed cDNA clones were used as targets to be hybridized with first strand cDNA probes that included 40 leukemia probes and 40 probes from different normal tissues. Leukemia probes were generated from cryopreserved samples obtained at the time of diagnosis from AML patients with poor outcome (patients who failed to achieve complete remission following conventional chemotherapy or relapsed within 6 month after remission) or good outcome (patients who achieved long term remission). To compare the gene expression profile between the diagnosis and relapse, probes were generated from AML samples obtained at the time of relapse. In addition, probes were derived from patients with CML in CP or BC, ALL at time of diagnosis, CLL at diagnosis or with refractory disease. To analyze gene expression during hematopoietic differentiation probes were generated from >95% pure fractions of CD34+, CD2+, CD14+, CD15+ and CD19+ cells derived from healthy individuals. Following microarray analysis, genes of potential interest were sequenced. Results identified 27 genes differentially overexpressed in leukemias including 22 known genes and 5 novel cDNA sequences. 24 genes were differentially underexpressed in leukemias, including 20 known genes and 4 novel cDNA sequences. Studies are in progress to correlate expression of these genes with prognostic factors and response to therapy (DFS and OS) and to confirm expression profile and prognostic relevance of these genes using Real-time PCR with a large panel of leukemia samples (n=120).

An analytical method based on the use of a liquid chromatograph equipped with a UV detector was developed for the determination of acifluorfen In soil and water. Acifluorfen was extracted from soil In methanol-0.10N NaOH (80 + 20 v/ v) and from water by partition with dlchloromethane. Solvent partitioning and solid-phase extraction were used to separate acifluorfen from major Interfering sample components. Average recoveries from soil at 1, 0.1, and 0.01 ppm fortification levels were 95.1 ± 3.4,92.6 ± 2.9, and 73.9 ± 3.0%, respectively. Recoveries from water spiked at levels from 0.01 to 1 ppm averaged 96.5 ± 5.4%. Method limits of detection were 0.006 ppm in soil and 0.003 ppm In water.

Genetic alterations, including genomic instability, represent possible steps towards a malignant transformation. One approach to delineate replication errors in cancer cells is to determine alterations of microsatellites that are short tandem repeat sequences dispersed throughout the human genome. We have investigated whether genomic instability may be a possible event in the leukemogenic process by evaluating the pattern of instability in 41 cases of childhood acute lymphoblastic leukemia (ALL).Eighty-two samples of genomic DNA (41 at diagnosis and 41 at remission) were analyzed by PCR with microsatellite markers chosen on five different chromosomes (2, 10, 11, 13, 18) known to be frequently involved in tumors of various origins. Since deletions of the short arm of chromosome 12 are relatively common in children with ALL, we also analyzed one region flanked by the microsatellite marker D12S308 on 12p. This area encompasses a genetic locus which contains the putative suppressor gene KIP1.A pattern of MI at one or two loci on different chromosomes could be documented in 4 of the 41 cases analyzed (9.7%). Three were common ALL and 1 was a T-ALL. One case showed two concomitant sites of instability, while 1 revealed two additional bands by using simultaneously microsatellite markers D2S123 and D18S58.These results indicate that genetic instability of microsatellite repeat sequences occurs in a proportion of childhood ALL. Mismatched repair errors documented in hereditary and sporadic solid tumors may thus be involved in hematological malignancies. While in such cases the pattern of genomic instability appears indicative of a mutator phenotype and of a potential predisposition towards a leukemic transformation, other genomic loci close to cytogenetic and molecular alterations known to occur in ALL need to be investigated in depth in cases with an apparently non mutated phenotype.

We have investigated the susceptibility of primary acute myeloid leukaemia (AML) samples to the lytic action of normal peripheral blood mononuclear cells (PBMC), as well as of the patients' autologous and allogeneic PBMC collected at the time of remission following stimulation with different concentrations of interleukin (IL)-2 and IL-12, both alone and in variable combinations. Primary AML blasts were resistant to IL-2-activated PBMC effectors generated from normal individuals, allogeneic and autologous patients in five, six and eight of the 10 AML samples tested, respectively, IL-12 alone proved ineffective in generating anti-leukaemic activity, whereas, in combination, the two cytokines induced anti-leukaemic killing in all five cases resistant to normal PBMC, in 4/6 samples resistant to allogeneic AML effectors and in 5/8 cases resistant to autologous effectors. In each case the lytic effect was maintained at the lowest cytokine combination (10 + 10 IU/ml) utilized. The suggestion of a synergistic effect was further strengthened by the evidence that at the lowest doses of IL-2 and IL-12 the degree of killing was greater than that promoted by each cytokine independently. The results of this study suggest that two major limitations associated with the administration of IL-2 to AML patients, the resistance of the blasts to IL-2-generated killing and the toxicity associated with high-dose IL-2, may be overcome by the combined use of very low doses of IL-2 and IL-12. As IL-2-resistant blasts may be lysed by a low-dose combination of IL-2/IL-12, feasibility studies with this cytokine combination are worthy of exploration in vivo.

Service quality evaluation is one of the main issues that have recently drawn managers’ and researchers’ attention. The definition of an evaluation standard not dependent on any particular service context has determined the popularity of many different quality tools. In this paper we show a comparative analysis of the affected tools that are widely used. These are summarized in an orientation map. Moreover we present some results of an experiment carried out with two of the major quality tools (SERVQUAL and QUALITOMETRO). The results identify good qualities as well as weaknesses for both tools. Possible improvement strategies are presented.