The study was approved by the Ethics Committee of the University of Lübeck (Lübeck, Germany) and all participants gave written informed consent in accordance with the Declaration find protocol of Helsinki. During this

double-blind, randomized study participants spent two experimental nights in the sleep laboratory (in addition to the adaptation night). On these nights, subjects arrived at the laboratory at 21:00 h for preparing blood sampling and polysomnographic recordings. Sleep was allowed between 23:00 h (lights off) and 7:00 h. Subjects received either 200 mg of spironolactone or placebo (orally) right before lights were turned off and a second dosage of spironolactone or placebo, respectively, at approximately 4:00 h. The second dosage was given to assure a high plasma concentration Ipilimumab cost of spironolactone during the second night half and early morning known to be associated with high levels of the endogenous MR ligands aldosterone and cortisol. To this end subjects in both experimental conditions were gently awakened between 3:45 and 4:15 h,

as soon as they had entered sleep stage 2. Awakenings from rapid eye movement (REM) sleep or slow wave sleep (SWS) were avoided. Blood was sampled first at 23:00 h and then every 1.5 h until 9:30 h via an intravenous forearm catheter which was connected to a long thin tube and enabled blood collection from an adjacent room without disturbing the subject’s sleep. To prevent clotting, approximately 700 mL of saline solution were infused during the experimental period. Blood samples were always processed immediately after sampling. Potential side effects of spironolactone were evaluated in the morning by questionnaires. Standard polysomnographic recordings were obtained to assure normal nocturnal sleep. Blood pressure

was assessed 30 min after awakening in the morning. Both conditions for a subject were separated by 2 weeks to assure clearance of the drug, and the order of conditions was balanced across subjects. Absolute counts of CD3+ total T cells, CD4+ T-helper cells, and CD8+ cytotoxic T cells as well as their naïve (CD45RA+CD62L+), central memory (CD45RA−CD62L+), effector memory (CD45RA−CD62L−), and (terminally differentiated) effector Montelukast Sodium (CD45RA+CD62L−) subsets were determined by a ‘lyse no-wash’ flow cytometry procedure. Briefly, 50 μL of an undiluted blood sample was immunostained with anti-CD3/APC-CY7, anti-CD8/PerCP, anti-CD4/PE-CY7, anti-CD62L/FITC, anti-CD45RA/PE, and anti-CD184 (CXCR4)/APC, in Trucount tubes (all from BD Biosciences, San Jose, CA). After 15 min of incubation at room temperature, 0.45 mL of fluorescence activated cell sorting (FACS) lysing solution (BD Biosciences) was added followed by incubation for 15 min. Finally, samples were mixed gently and at least 10 000 CD3+ cells were acquired on a FACSCalibur using DIVA Software (BD Biosciences).

„Moczenie nocne u dzieci w wieku szkolnym (7–15 lat) uczących się w szkołach podstawowych miasta i gminy Wyrzysk”, której promotorem był prof. Olgierd Sarrazin. Aleksander Napierała był również członkiem Zarządu Bydgosko-Pilskiej Izby Lekarskiej oraz członkiem Polskiego Towarzystwa Lekarskiego (PTL) i Polskiego Towarzystwa Alergologicznego (PTA). Od 1978 roku współpracował z Zarządem miejscowego Klubu Sportowego „Łobżonka”, bezinteresownie sprawując opiekę medyczną nad zawodnikami. Jego zdolności organizacyjne i pasja działania znalazły wyraz również w organizacji

Pirfenidone in vitro w Wyrzysku w latach 1979–1999 co najmniej 10 sympozjów naukowo-szkoleniowych o różnej tematyce i zasięgu niejednokrotnie pozaregionalnym, na które zapraszał wykładowców o uznanym autorytecie w kraju. Np. w 1988 roku przy współpracy miejscowego Koła PTL i firmy SANDOZ przygotowano sympozjum poświęcone astmie oskrzelowej, w którym uczestniczyło 83 lekarzy z kilku sąsiednich województw. Wymiernym efektem tego spotkania było założenie pierwszego w Pilskiem Koła PTA. Do dziś jest to ewenement w skali kraju, aby miasto na poziomie gminy, liczące nieco powyżej www.selleckchem.com/JNK.html pięć tysięcy mieszkańców, mogło zdobyć się na zorganizowanie cyklu takich spotkań medyków z całego regionu. Interesując się problemami regionu,

w 1991 roku Aleksander Napierała kandydował również do sejmu z listy SD, a później Unii Wolności. W sygnalizowanym programie reprezentował opinię, że w sejmie nie jest doceniana rola małych aglomeracji miejskich, w których żyje około 28% ludności. Dlatego zamierzał poświęcić swoją działalność problemom tych środowisk, zwłaszcza w dziedzinach wychowania, kultury i zdrowia. Uważał, że „oszczędzanie na wychowaniu i zdrowiu jest jednoznaczne

z podcinaniem gałęzi, na której się siedzi”. Uchwałą Rady Państwa został odznaczony Brązowym (1984) i Złotym (1990) Krzyżem Zasługi. Poza tym wyróżniono go Złotą Odznaką Honorową „Za zasługi w rozwoju województwa pilskiego” (1982) i Złotą Odznaką Honorową Polskiego Związku Niewidomych (1985). Dr med. Aleksander Napierała zmarł nagle 25 czerwca 1999 roku w czasie pełnienia dyżuru lekarskiego na Oddziale Dziecięcym miejscowego szpitala, dwa dni po obronie pracy doktorskiej. Pozostawił żonę Krystynę oraz córkę Monikę (1976) i syna Łukasza (1982). Żegnało go liczne grono Amisulpride współpracowników, a także rodzice i dzieci, którym zawsze służył pomocą. Spoczywa na cmentarzu parafialnym w Wyrzysku. W Wyrzysku był postacią bardzo popularną. Darzono go powszechną sympatią, nie tylko jako lekarza pediatrę, ratującego zdrowie i życie dzieci, ale także jako człowieka niezwykle komunikatywnego o dużym optymizmie życiowym, który angażował się w wiele inicjatyw społecznych na rzecz regionu, przede wszystkim dzieci. Docenili to także sportowcy, którzy co roku organizują ogólnopolski „bieg Olka” m.in. dla dzieci i młodzieży (w różnych grupach wiekowych na różnych dystansach), poświęcony jego pamięci.

Gas mixing during transport typically does not cause problems for the read out of the stored spatial information as long as there is no mixing between the individual point-by-point experiments. The main advantage of this technique is that the encoding and detection regions can be independently optimized, the former for versatility of the encoding and the latter can be optimized for sensitivity. An increased sensitivity could be achieved VX-809 order using a coil that may be smaller than the actual sample leading to an improved filling factor and the detection field strength may be higher than in the sample region. This scheme allows for samples to be used that could not be measured sensitively in an NMR experiment,

such as a magnetic porous material. The mobile

phase can be encoded within this porous substance while the detection will be spatially removed from the material. Alternatively, detection methods that are not based on Faraday inductive detection may be employed to provide Enzalutamide cost higher sensitivity [113] and [114]. While remote detection does not contain a direct spectral or imaging dimension, the arrival of the encoded gas can be monitored transiently, thereby retrieving time-of-flight information in a direct dimension. This enables visualization of flow and diffusion through, for example, a porous rock sample [115] or through microfluidic devices [116] and [117]. The gas from various regions (and therefore the encoded information) may arrive at different times (of flight) as shown in Fig. 11. The 129Xe chemical shift can also be

utilized in remotely detected MRI to separate between different environments of the gas Dolichyl-phosphate-mannose-protein mannosyltransferase flowing through porous systems [118]. Perhaps most interesting for biomedical applications, is that the remote detection concept can be extended to MRI of dissolved xenon with detection after extraction from the liquid to the gas phase via membranes [119]. Remote detection of hp gases can also be utilized for relaxation measurements and may be particularly useful for field dependent relaxometry studies [120]. As a note of caution, remote detection suffers from the absence of a direct dimension (i.e. there is no frequency encoding) because the information has to be collected point by point. For instance, a 64 × 64 two-dimensional MR image requires a minimum of 4096 scans as opposed to 64 scans for directly detected MRI. On the other hand, time-of-flight information can be recorded transiently, which facilitates a different type of direct dimension than in conventional Fourier imaging techniques. Therefore continuous flow type of experiments are probably most practical for remote detection. Further, remote detection also requires that fluctuations in the gas delivery and spin polarization are kept at a minimum although calibration experiments can sometimes correct for such fluctuations [120].

As shown in Fig. 2, rates of recanalization in the PROACT II study were quite similar to those obtained in the sonothrombolysis with TCCS and rtPA study. The PROACT II study randomized patients with MCA main stem or M2 branch occlusions within a 6-h time window for intra-arterial thrombolysis with pro-urokinase. The sonothrombolysis with TCCS and IV rtPA study randomized patients with proximal MCA main stem occlusions without residual flow (including patients with additional ipsilateral internal carotid artery occlusion) within a 3-h time window for 1 h of continuous insonation. As shown in Fig. 3, comparable

outcome results after 3 months (3–4 months in PROACT II) were obtained for the sonothrombolysis Nivolumab in vitro with TCCS and IV rtPA group and the pro-urokinase treatment group. The strong tendency toward a worse outcome for patients in the IV rtPA group without sonothrombolysis compared with those in the PROACT II control group may indicate that patients in the Lübeck randomized study may have been more severely affected than those in the PROACT II study. The lack of a temporal bone window is one main limitation of sonothrombolysis. Research studies have revealed that the frequency of an insufficient temporal sound

window for TCCS can vary from 8% [12] to 27% [13]. On the other hand, also the interventional therapy may not be applicable for all patients. A common limitation of interventional therapy is the lack of patency of the proximal carotid artery. PLX3397 solubility dmso Data from the own register of MCA-M1 occlusions have revealed the presence of an additional proximal occlusion of the internal carotid artery in 23% of patients (unpublished data). A meta-analysis conducted by Tsivgoulis et al. [3] on sonothrombolysis with transcranial US (TCCS or TCD) included over 400 patients. They found that in comparison to patients with this website rtPA treatment alone, patients who underwent sonothrombolysis had a 3 times higher chance for complete recanalization and a 2 times higher chance

for non-disability after 3 months. There was no evidence for increased risk of cerebral bleeding with US treatment. When the thrombolytic effect of “diagnostic” transcranial US was clinically observed for the first time, no experimental data on the effect of high-frequency, low-energy PW US on thrombolysis were available at the time. However, during the 1990s (after much time had passed since the first description of the thrombolytic effect of US in the late 1970s [14]), in vitro studies using high-frequency (1 MHz) and high-energy (spatial peak temporal average intensity [ISPTA] of 2 W/cm2) US demonstrated improved US-mediated binding of rtPA to fibrin, as well as reversible disintegration of fibrin without thrombolytics [15].

07 Full-size table Table options View in workspace Download as CSV “
“The optimum surveillance intervals following complete elimination of intestinal metaplasia (CEIM) by radiofrequency ablation (RFA) for Barrett’s esophagus (BE) are unknown, and practices

vary between institutions. We used data from a nationwide, multicenter registry of patients treated with RFA to assess surveillance ABT-737 in vitro practices in community and academic settings following successful ablation. Using the U.S. RFA Registry, we reviewed patients with BE who had achieved CEIM by RFA between July 2007 and November 2012. The onset of the surveillance period was defined as the date of histologic confirmation of CEIM. Ruxolitinib molecular weight Pre-ablation histology and endoscopic surveillance information were obtained from registry records. The frequency of esophagogastroduodenoscopies (EGDs) and time to first EGD after attaining CEIM were assessed in both community and academic settings. We used Student’s t-test to examine

differences between the frequency of EGDs performed in community and academic settings. Among 3724 patients who achieved CEIM after RFA, 2285 (61%) were followed up by endoscopic surveillance. Surveillance was practiced in 1539 of 2634 (58%) patients in community settings and 746 of 1090 (68%) patients in academic settings (p<0.001). The mean time to first EGD after CEIM was 9.8 ± 6.1 months for all CEIM patients. Subjects with more advanced histology had their initial surveillance endoscopy sooner than those with non-dysplastic disease, with a mean interval to first EGD of 11.4 ± 6.6, 9.2 ± 5.4, and 7.5 ± 5.0 months for no dysplasia, LGD, and HGD patients, respectively. For patients who received RFA in the community setting, the mean

number of EGDs Uroporphyrinogen III synthase with biopsy performed was 0.4 ± 0.6 during the first year following CEIM. For patients who received RFA in the academic setting, the mean number of EGDs with biopsy performed was 0.7 ± 0.8 during the first year following CEIM. In general, the first EGD with biopsies after CEIM occurred sooner in the academic setting than in community practice. With respect to the intervals between surveillance biopsy sessions, biopsies were performed every 11.6 months (interquartile range (IQR): 8.0-13.7) for CEIM patients in community-based settings, but more frequently in the academic setting (every 8.9 months, IQR: 6.2-11.8). In patients with BE who had achieved complete eradication of IM by RFA, endoscopic surveillance was generally less frequent in real-life settings than is reported in the literature. Surveillance occurred in a higher proportion of patients treated in academic settings, and occurred at shorter intervals compared to community practices. Long-term follow-up of this cohort will allow assessment of the efficacy of more attenuated surveillance periods. Endoscopic Surveillance after First CEIM in Academic vs.

This work presents a study regarding Alectinib solubility dmso total vitamin C and ascorbic acid degradation in acerola pulp during thermal treatment by ohmic and conventional heating. For the ohmic heating technology, the ascorbic acid degradation ranged from 3.08 to 10.63%. The applied voltage and the solids content of the pulp significantly influenced the degradation of the compounds. The voltage gradient had a positive effect, i.e., an increase in the voltage gradient lead to an increase in the AA degradation. The

total vitamin C degradation ranged from 2.0 to 5.1%. The vitamin C degradation was influenced only by the linear and the quadratic effects of the voltage. Ohmic heating, when performed with low voltage gradients, exhibited vitamin C and ascorbic acid degradation similar to conventional heating. However, high voltage gradients increased the degradation of both vitamin C and ascorbic acid. This behavior may be explained by the increase of electrochemical reactions when using high voltage gradients, which can adversely affect the ascorbic acid and catalyze the degradation pathways in the presence

of oxygen. The authors acknowledge the financial support received from CNPq (Conselho Nacional de Desenvolvimento Científico Apitolisib e Tecnológico, Brasil), as a scholarship to the first author, from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil) within the PRODOC project, and Mais Fruta Company for supplying the acerola pulp. “
“Thermal processing is one of the most widely used physical ADAMTS5 methods for food preservation. High temperature inactivates undesired microorganisms and enzymes, but also deteriorates quality and sensorial attributes. Consumer demands for minimally

processed products compel food companies to optimize and redesign the existing technologies. In this context, the assessment of the process impact in terms of food safety and quality is of great importance for process evaluation and design. The in situ evaluation of microbial count or vitamin content is often time-consuming and expensive. Alternatively, the effect of the thermal processing can be evaluated in two ways: from the analysis of the time-temperature history and the residence time distribution coupled with the kinetics of thermal change; and from the use a time-temperature integrator (TTI) as indicator of safety and quality ( Lewis & Heppell, 2000, p. 447; Van Loey, Hendrickx, De Cordt, Haentjens, & Tobback, 1996). The first method requires the time-temperature history, which can be recorded online at the processing plant and also residence time distribution techniques. These results, combined with the knowledge of the thermal change kinetics, allow the calculation of the process impact.

This correlation data indicate that when CD45RA down-regulates at the end see more of the naïve stage, CCR7 is indeed down-regulated, while CD28 is minimally up-regulated (see

Fig. 4B, blue hatched arrows). Our data are not consistent with the supposition that there is an extra stage as determined by CD45RA−CCR7+CD28+ ( Appay et al., 2002). Events with this phenotype captured by a gating strategy are most likely a mixture of naïve and CM events as defined by this analysis. The CD8+ average model also supports the hypothesis that when CD28 is down-regulated, CD45RA begins to be up-regulated (red arrows, r = 0.56, p < 0.01 with a difference of 1.9 (NS)). The last EF stage, is defined as the point at which the up-regulation of CD45RA has ended. During the developmental progression of memory and effector T cells, a subset of cells may begin to preferentially express markers that might not be expressed in the remaining cells. In PSM, the heterogeneous expression of markers can be visualized with branching expression profiles (see Fig. 5). Fig. 5A shows a progression schematic similar to Fig. 1 but includes a simple branch involving feature C. In this example, when cells reach the checkpoint where feature B is up-regulated, 70% of the cells also up-regulate feature C, while 30%

do not. Fig. 5B delineates the three probability state model EPs that model this simple branch (top = feature A, middle = feature B, and bottom = feature C). Fig. 5C summarizes this progression in the probability state model progression plot, which includes the branching of feature C (see the CB label). Fig. 5D

shows the associated probability Glycogen branching enzyme state model surface dot plots for click here feature A vs. B (top), feature A vs. C (middle), and feature B vs. C (bottom). Note that branches are not always visible in dot plots, which is why they have been traditionally difficult to detect. Branches are relatively easy to determine with PSM since non-branched EPs are incompatible with branched data, resulting in a dramatic loss of classified events and poor fitting. In this simple example, the branch point is at the end of Stage 2. However, when modeling T-cell branches, the location might be elsewhere along the progression axis. An averaged model featuring 22 samples from healthy donors was used to identify branched markers. Each sample was stained with antibodies against CD3, CD4, CD8, CD45RA, CD28, CCR7 (CD197), CD27, CD62L, CD57, and CD127. Fig. 6 shows the stratification expression profiles of CD45RA, CCR7, and CD28 as well as four branched EPs for CD62L, CD27, CD127, and CD57. Here, CD62L (l-selectin) has a 77% (9%) chance of down-regulating slightly before the end of the naïve stage and correlates best with the down-regulation of CCR7 (blue hatched arrows, r = 0.81, p < 0.00001, diff = − 4.23, NS). CD27 slightly down-regulates with CD45RA and CCR7 at the end of the naïve stage and then has a 75% (17%) chance of fully down-regulating in the middle of the CM stage.

To this end, and as part of an ongoing review, Environment Canada’s Disposal at Sea Program hosted a Contaminated Dredged Material Management Decisions Workshop in 2006. The workshop brought together over

50 sediment assessment and management experts from academic, industrial, and regulatory backgrounds and charged them with drafting a potential framework to assess contaminated DMs and compare the risks of various disposal alternatives. The selleck compound resulting recommendations concerned the development of sediment assessment tools, the interpretation of these tools, and the essential attributes of a comparative risk assessment process for DM management (Agius and Porebski, 2008). The workshop participants strongly recommended the development of a national dredging or sediment management strategy, and proposed an expanded decision-making framework for the tiered assessment of dredged materials www.selleckchem.com/products/fg-4592.html and for the comparative assessment of disposal

options for those sediments deemed to be unsuitable for ocean disposal (Fig. 1). Specific recommendations to improve chemical assessments included: • Inclusion of a broader suite of metals (or even a full metal scan) rather than just Cd and Hg, in Tier 1 assessments. It was recognized that the implementation of these recommendations would require the development and application of new, analyte-specific LALs, and, potentially

chemical UALs that are compatible with EC’s DaS sample handling, extraction and analysis protocols. Since the workshop, EC has sought advice externally and carried out work internally to address a range of issues in support of framework revisions (Agius and Porebski, 2008, Apitz, 2008, Apitz, 2010, Golder, 2008, Mudroch and Agius, 2011 and Vogt, 2009). These studies generated broad-ranging advice and options by evaluating the scientific underpinnings of various assessment and decision tools, and reviewing international policy and practice on various aspects Bupivacaine of DM frameworks. Based upon the workshop recommendations, Apitz, 2008 and Apitz, 2010 reviewed the use of various chemical, biological and decision tools in a Tier 1 assessment. A range of options were reviewed, but it was pointed out that many options were interdependent and that the optimal choices would depend upon a range of policy choices by EC, informed by available science. In particular, the regulatory implications of various choices on chemical approaches would be dependent upon the list of chemicals considered, the decision rules applied, and the role of bioassays in the tiered approach.

According to Evans et al. [10] and Cerniglia and Yang [4], similar to naphthalene degradation pathway, catechol also degraded to simple aliphatic compounds. Though naphthalene has been identified as one of the degraded products in the present study, the presence of di-hydroxy anthracene and anthraquinone reveals that the catabolism has been realized through dioxygenase system of the isolate. The initial enzymatic attack at C-1 and C-2 position

observed in the present study showed similarity with the naphthalene dioxygenase system. Though complete degradation of anthracene by Pseudomonas, Sphingomonas, Nocardia, Beijerinckia, Rhodococcus and Mycobacterium [9], [10] and [19] in the presence of external surface-active agent, nevertheless, in the present study, in situ production Target Selective Inhibitor Library cost of surface-active agent mediates the degradation as observed. Further, the presence of anthracene and the process of degradation tremendously altered the cell Selleckchem Palbociclib volume. The modification of cell surface morphology with reference to external stress was observed in both Gram −ve

bacteria and Gram +ve bacteria. An extensive filamentous growth of B. licheniformis was observed when grown in the presence of organic solvents and a toxic compound [28] and suggested that this kind of filamentation of a bacterial cell reduces the environmental stress and also helps in communicating and exchange the information. However, the observations made in the present study suggested that the continuous flow of the molecules by selective permeability Ergoloid of cell membrane of MTCC 5514 and the micelle and reverse micellar aggregations occurs in the lipid bilayer as shown schematically ( Scheme 1), reflected as increase in cell volume, however, the said hypothesis,

further needs explorations. In addition, the increase in cell volume may also be reasoned to the chemotaxis behavior of the isolate MTCC 5514. Though, the degradation was ascertained based on the release of degradation of products, the actual degradation mechanism can be explained schematically. Since, it has been observed that, biosurfactant, pH, intra/extra cellular and degradative enzymes, temperature, shaking condition and concentration of the test compound played the significant role in the degradation observed, Scheme 1 convey the actual steps followed during the degradation studies. In brief, once the target molecule intended to the external medium, the presence of surface-active agents result with the formation of micelles and by selective permeability, micelles containing the anthracene molecule make an entry into the lipid bi-layer.

We observed that these metabolites did not change these activities (CK: μmol creatine min−1 mg protein−1: n = 7; control: 4.33 ± 0.81; Orn: 5.31 ± 0.97; Hcit: 4.48 ± 0.67; NaK: nmol Pi min−1 mg protein−1: n = 4; control: 209.8 ± 71.7; Orn: 207.5 ± 42.2; Hcit: 258.3 ± 28.2). Patients affected by this HHH syndrome commonly have neurological dysfunction with acute encephalopathy, ataxia, choreoathetosis, developmental delay, severe muscle spasticity and mental retardation, whose neuropathology is poorly known (Shih et al., 1969 and Valle and Simell, 2001). Interestingly, patients with HHH syndrome and argininemia present similarities

in clinical features, with progressive neurological deterioration and pyramidal signs that are usually not associated with hyperammonemic decompensation (Korman et al., 2004, Marescau et al., 1990 and Salvi et al., 2001; ABT-737 concentration Valle and Simell, 2001). Furthermore, it has been suggested that the lower limb dysfunction

observed in HHH syndrome, and also in argininemia, may be related to an altered polyamine metabolism (Shimizu et al., 1990). On the other hand, many individuals with HHH syndrome present mitochondrial abnormalities, as well as accumulation and excretion of lactic acid, ketone bodies and CAC intermediates (Gatfield et al., 1975, Haust et al., 1981, Metoki et al., 1984 and Salvi et al., 2001), indicating an impaired mitochondrial function. Therefore, in the current study we evaluated the in vivo effects of these learn more amino acids accumulating in HHH syndrome on important biochemical parameters of mitochondrial homeostasis, particularly those related to bioenergetics and biological oxidations in cerebral cortex of young rats in order to provide mechanistic insights for HHH syndrome Uroporphyrinogen III synthase neuropathology. We first verified that Orn and Hcit in vivo administration to rats increased

TBA-RS levels, as compared with control animals. These results corroborate our previous in vitro findings ( Amaral et al., 2009). Since TBA-RS measurement reflects the amount of malondialdehyde formation, an end product of membrane fatty acid peroxidation ( Halliwell and Gutteridge, 2007), the increased values of this parameter elicited by Orn and Hcit strongly indicates that these amino acids caused lipid peroxidation in vivo. Orn, and also Hcit to a higher degree, enhanced carbonyl formation, implying that they caused protein oxidation. In this scenario, carbonyl groups (aldehydes and ketones) are mainly produced by oxidation of protein side chains (especially Pro, Arg, Lys, and Thr), by oxidative cleavage of proteins, or by the reaction of reducing sugars or their oxidation products with lysine protein residues (Dalle-Done et al., 2003). However, we cannot also exclude the possibility that aldehydes resulting from lipid peroxidation may also induce carbonyl generation (Dalle-Done et al., 2003).