982 resultados para No Exit


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Semi-presidential systems of democratic governance risk ending up in a stalemate when it is not clear which of the two „heads” – head of State or head of Government – shall take the lead. The current political situation in Romania features some of the commonly observed characteristics of such an institutional blockade. However, after addressing these formal aspects of political Romania, the author argues for not forgetting to take into account the informal, actor-related factors. The nature of the Romanian political parties and party system seems to hinder the finding of a consensus needed to exit the self-imposed blockade. More specifically, it is the Democratic Party (PD) that is the key to understanding the recent developments. The Government of April the third has yet to prove its efficiency.

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We investigate numerically the effects of nozzle-exit flow conditions on the jet-flow development and the near-field sound at a diameter-based Reynolds number of Re D = 18 100 and Mach number Ma = 0.9. Our computational setup features the inclusion of a cylindrical nozzle which allows to establish a physical nozzle-exit flow and therefore well-defined initial jet-flow conditions. Within the nozzle, the flow is modeled by a potential flow core and a laminar, transitional, or developing turbulent boundary layer. The goal is to document and to compare the effects of the different jet inflows on the jet flow development and the sound radiation. For laminar and transitional boundary layers, transition to turbulence in the jet shear layer is governed by the development of Kelvin-Helmholtz instabilities. With the turbulent nozzle boundary layer, the jet flow development is characterized by a rapid changeover to a turbulent free shear layer within about one nozzle diameter. Sound pressure levels are strongly enhanced for laminar and transitional exit conditions compared to the turbulent case. However, a frequency and frequency-wavenumber analysis of the near-field pressure indicates that the dominant sound radiation characteristics remain largely unaffected. By applying a recently developed scaling procedure, we obtain a close match of the scaled near-field sound spectra for all nozzle-exit turbulence levels and also a reasonable agreement with experimental far-field data.

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The coordinated exit of intracellular pathogens from host cells is a process critical to the success and spread of an infection. While phospholipases have been shown to play important roles in bacteria host cell egress and virulence, their role in the release of intracellular eukaryotic parasites is largely unknown. We examined a malaria parasite protein with phospholipase activity and found it to be involved in hepatocyte egress. In hepatocytes, Plasmodium parasites are surrounded by a parasitophorous vacuole membrane (PVM), which must be disrupted before parasites are released into the blood. However, on a molecular basis, little is known about how the PVM is ruptured. We show that Plasmodium berghei phospholipase, PbPL, localizes to the PVM in infected hepatocytes. We provide evidence that parasites lacking PbPL undergo completely normal liver stage development until merozoites are produced but have a defect in egress from host hepatocytes. To investigate this further, we established a live-cell imaging-based assay, which enabled us to study the temporal dynamics of PVM rupture on a quantitative basis. Using this assay we could show that PbPL-deficient parasites exhibit impaired PVM rupture, resulting in delayed parasite egress. A wild-type phenotype could be re-established by gene complementation, demonstrating the specificity of the PbPL deletion phenotype. In conclusion, we have identified for the first time a Plasmodium phospholipase that is important for PVM rupture and in turn for parasite exit from the infected hepatocyte and therefore established a key role of a parasite phospholipase in egress.

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A heterozygous mutation (c.643C>A; p.Q215X) in the monocarboxylate transporter 12-encoding gene MCT12 (also known as SLC16A12) that mediates creatine transport was recently identified as the cause of a syndrome with juvenile cataracts, microcornea, and glucosuria in a single family. Whereas the MCT12 mutation cosegregated with the eye phenotype, poor correlation with the glucosuria phenotype did not support a pathogenic role of the mutation in the kidney. Here, we examined MCT12 in the kidney and found that it resides on basolateral membranes of proximal tubules. Patients with MCT12 mutation exhibited reduced plasma levels and increased fractional excretion of guanidinoacetate, but normal creatine levels, suggesting that MCT12 may function as a guanidinoacetate transporter in vivo. However, functional studies in Xenopus oocytes revealed that MCT12 transports creatine but not its precursor, guanidinoacetate. Genetic analysis revealed a separate, undescribed heterozygous mutation (c.265G>A; p.A89T) in the sodium/glucose cotransporter 2-encoding gene SGLT2 (also known as SLC5A2) in the family that segregated with the renal glucosuria phenotype. When overexpressed in HEK293 cells, the mutant SGLT2 transporter did not efficiently translocate to the plasma membrane, and displayed greatly reduced transport activity. In summary, our data indicate that MCT12 functions as a basolateral exit pathway for creatine in the proximal tubule. Heterozygous mutation of MCT12 affects systemic levels and renal handling of guanidinoacetate, possibly through an indirect mechanism. Furthermore, our data reveal a digenic syndrome in the index family, with simultaneous MCT12 and SGLT2 mutation. Thus, glucosuria is not part of the MCT12 mutation syndrome.

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Divalent metal transporter-1 (SLC11A2/DMT1) uses the H+ electrochemical gradient as the driving force to transport divalent metal ions such as Fe2+, Mn2+ and others metals into mammalian cells. DMT1 is ubiquitously expressed, most notably in proximal duodenum, immature erythroid cells, brain and kidney. This transporter mediates H+-coupled transport of ferrous iron across the apical membrane of enterocytes. In addition, in cells such as to erythroid precursors, following transferrin receptor (TfR) mediated endocytosis; it mediates H+-coupled exit of ferrous iron from endocytic vesicles into the cytosol. Dysfunction of human DMT1 is associated with several pathologies such as iron deficiency anemia hemochromatosis, Parkinson's disease and Alzheimer's disease, as well as colorectal cancer and esophageal adenocarcinoma, making DMT1 an attractive target for drug discovery. In the present study, we performed a ligand-based virtual screening of the Princeton database (700,000 commercially available compounds) to search for pharmacophore shape analogs of recently reported DMT1 inhibitors. We discovered a new compound, named pyrimidinone 8, which mediates a reversible linear non-competitive inhibition of human DMT1 (hDMT1) transport activity with a Ki of ∼20 μM. This compound does not affect hDMT1 cell surface expression and shows no dependence on extracellular pH. To our knowledge, this is the first experimental evidence that hDMT1 can be allosterically modulated by pharmacological agents. Pyrimidinone 8 represents a novel versatile tool compound and it may serve as a lead structure for the development of therapeutic compounds for pre-clinical assessment.

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PURPOSE The Geographic Atrophy Progression (GAP) study was designed to assess the rate of geographic atrophy (GA) progression and to identify prognostic factors by measuring the enlargement of the atrophic lesions using fundus autofluorescence (FAF) and color fundus photography (CFP). DESIGN Prospective, multicenter, noninterventional natural history study. PARTICIPANTS A total of 603 participants were enrolled in the study; 413 of those had gradable lesion data from FAF or CFP, and 321 had gradable lesion data from both FAF and CFP. METHODS Atrophic lesion areas were measured by FAF and CFP to assess lesion progression over time. Lesion size assessments and best-corrected visual acuity (BCVA) were conducted at screening/baseline (day 0) and at 3 follow-up visits: month 6, month 12, and month 18 (or early exit). MAIN OUTCOME MEASURES The GA lesion progression rate in disease subgroups and mean change from baseline visual acuity. RESULTS Mean (standard error) lesion size changes from baseline, determined by FAF and CFP, respectively, were 0.88 (0.1) and 0.78 (0.1) mm(2) at 6 months, 1.85 (0.1) and 1.57 (0.1) mm(2) at 12 months, and 3.14 (0.4) and 3.17 (0.5) mm(2) at 18 months. The mean change in lesion size from baseline to month 12 was significantly greater in participants who had eyes with multifocal atrophic spots compared with those with unifocal spots (P < 0.001) and those with extrafoveal lesions compared with those with foveal lesions (P = 0.001). The mean (standard deviation) decrease in visual acuity was 6.2 ± 15.6 letters for patients with image data available. Atrophic lesions with a diffuse (mean 0.95 mm(2)) or banded (mean 1.01 mm(2)) FAF pattern grew more rapidly by month 6 compared with those with the "none" (mean, 0.13 mm(2)) and focal (mean, 0.36 mm(2)) FAF patterns. CONCLUSIONS Although differences were observed in mean lesion size measurements using FAF imaging compared with CFP, the measurements were highly correlated with one another. Significant differences were found in lesion progression rates in participants stratified by hyperfluorescence pattern subtype. This large GA natural history study provides a strong foundation for future clinical trials.

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Mineralocorticoids (DOCA) are known to increase Na('+) absorption and K('+) secretion in the rabbit cortical collecting duct (CCD). However, the mechanism of regulation of the apical and basolateral cell membranes and tight junction ion conductive pathways (G('a), G('b), and G('tj), respectively) by mineralocorticoids are only partially understood. Using electrophysiological techniques and microelectrodes it was demonstrated that the apical cell membrane contained a dominant Ba('2+) sensitive K('+) conductive pathway, G(,K)('a), and an amiloride sensitive Na('+) conductive pathway, G(,Na)('a). The basolateral membrane contained a dominant Cl('-) conductive pathway, G(,Cl)('b), and a significant Ba('2+) sensitive K('+) conductive pathway, G(,K)('b). Upon elevating the mineralocorticoid levels of rabbits with intact adrenal glands it was found that V('te) was significantly increased after 1 day with a further increase after 13-16 days. These results indicated both primary and secondary effects of mineralocorticoid elevation. After 1 day of DOCA treatment, G(,Na)('a), I(,Na)('a) and I(,K)('a) increased by more than 2-fold and were maintained at high levels after 13-16 days of DOCA treatment. Secondary (chronic) effects of mineralocorticoids were evident after 4 days or more of DOCA treatment. These included a significant increase in G(,K)('a) from 4.0 to 10.2 mS.cm('-2) and a hyperpolarization of V('b) by -20 mV after 4 days of treatment. After 13-16 days of DOCA treatment V('b) remained hyperpolarized at -98.1 mV and G('tj) decreased from 5.6 to 4.2 mS.cm('-2). The hyperpolarization of V('b) was due to an increase in electrogenic Na('+) pump activity as the pump current, I(,act)('b), increased significantly from 35.7 to 195.2 (mu)A.cm('-2). Whereas net passive K('+) current across the basolateral membrane, I(,K)('b), was near zero in the control group of animals, i.e., K('+) near equilibrium, I(,K)('b) was approximately -40 (mu)A.cm('-2) in chronic DOCA treated animals. These results demonstrate that the initial effect of mineralocorticoid elevation is to increase G(,Na)('a). The ensuing depolarization of the apical membrane increases the driving force for K('+) exit into the lumen. Between 1 and 4 days of elevation, G(,K)('a) more than doubles in magnitude and at the same time the electrogenic activity of the Na('+) pump increases. This results in a hyperpolarization of V('b) which increases the driving force for K('+) uptake from the bath to the cell through a basolateral membrane conductive pathway. After 13-16 days G('tj) decreases thereby serving to maintain high electrochemical gradients across the epithelium. Therefore, the long term effects of mineralocorticoid elevation on the CCD appear to be adaptive mechanisms that serve to maintain high levels of K('+) secretion and Na('+) absorption. ^

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This paper considers the aggregate performance of the banking industry, applying a modified and extended dynamic decomposition of bank return on equity. The aggregate performance of any industry depends on the underlying microeconomic dynamics within that industry . adjustments within banks, reallocations between banks, entry of new banks, and exit of existing banks. Bailey, Hulten, and Campbell (1992) and Haltiwanger (1997) develop dynamic decompositions of industry performance. We extend those analyses to derive an ideal decomposition that includes their decomposition as one component. We also extend the decomposition, consider geography, and implement decomposition on a state-by-state basis, linking that geographic decomposition back to the national level. We then consider how deregulation of geographic restrictions on bank activity affects the components of the state-level dynamic decomposition, controlling for competition and the state of the economy within each state and employing fixed- and random-effects estimation for a panel database across the fifty states and the District of Columbia from 1976 to 2000.

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This paper considers the aggregate performance of the banking industry, applying a modified and extended dynamic decomposition of bank return on equity. The aggregate performance of any industry depends on the underlying microeconomic dynamics within that industry --- adjustments within banks, reallocations between banks, entry of new banks, and exit of existing banks. Bailey, Hulten, and Campbell (1992) and Haltiwanger (1997) develop dynamic decompositions of industry performance. We extend those analyses to derive an ideal dynamic decomposition that includes their dynamic decomposition as one component. We also extend the decomposition, consider geography, and implement decomposition on a state-by-state basis, linking that geographic decomposition back to the national level. We then consider how deregulation of geographic restrictions on bank activity affects the components of the state-level dynamic decomposition, controlling for competition and the state of the economy within each state and employing fixed- and random-effects estimation for a panel database across the fifty states and the District of Columbia from 1976 to 2000.

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The intensification of consequential testing situations is associated with an increase in anxiety among American students (Casbarro, 2005). Test anxiety can have negative effects on student test performance (Everson, Millsap, & Rodriguez, 1991). If test anxiety has the potential to decrease students’ test scores, it becomes a factor that can threaten the validity of any inferences drawn between test scores and student progress (Cizek & Burg, 2006). There are several factors that relate closely to test anxiety (Cizek & Burg, 2006). Variables of key influence include gender, socioeconomic status, and teacher-manifested anxiety (Hembree, 1988). Another influence upon test anxiety is students’ participation in academic support programs to prepare them for exit examinations. The purpose of this study was to examine the relationship between 10th grade high school student gender, socioeconomic status, perceived teacher anxiety, and student preparedness with levels of the Massachusetts Comprehensive Assessment System (MCAS) test anxiety. It appears that few studies have examined levels of high school test anxiety in regards to this specific high-stakes MCAS exit exam required for high school graduation. A two-phase sequential mixed-methods research design was used to survey (N=156) 10th grade students represented by a sampling of (n=80) students with low socioeconomic status and (n=76) students with high socioeconomic status regarding their levels of test anxiety in relation to upcoming MCAS testing. A multiple regression analysis was used to measure the relationship between the predictor variables (gender, socioeconomic status, perceived teacher anxiety, and student preparedness) with the criterion variable of student test anxiety using the Test Anxiety Inventory (TAI). Personal interviews with (n=20) volunteer students provided rich explanations of students’ academic self-efficacy, their perceptions of their performance on the upcoming MCAS exam, and their use of strategies to reduce their levels of test anxiety. Personal interviews with (n=12) volunteer school administrators and teachers provided descriptions of their perceptions of how test anxiety affected their students’ performance. A major quantitative finding of this study was that the variables of student socioeconomic status and student ratings of teacher anxiety accounted for the variance in students’ levels of surveyed test anxiety (R2 = .06, p = .033, small to medium effect size). These results indicate that different student populations vary in their readiness skills to successfully participate in consequential testing situations. Consequently, high-test anxious students would require emotional preparation as well as academic preparation when confronting high-stakes testing. The results have the potential to re-shape the format of schools’ MCAS test preparation efforts.

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The purpose of this work was to develop a comprehensive IMSRT QA procedure that examined, using EPID dosimetry and Monte Carlo (MC) calculations, each step in the treatment planning and delivery process. These steps included verification of the field shaping, treatment planning system (RTPS) dose calculations, and patient dose delivery. Verification of each step in the treatment process is assumed to result in correct dose delivery to the patient. ^ The accelerator MC model was verified against commissioning data for field sizes from 0.8 × 0.8 cm 2 to 10 × 10 cm 2. Depth doses were within 2% local percent difference (LPD) in low gradient regions and 1 mm distance to agreement (DTA) in high gradient regions. Lateral profiles were within 2% LPD in low gradient regions and 1 mm DTA in high gradient regions. Calculated output factors were within 1% of measurement for field sizes ≥1 × 1 cm2. ^ The measured and calculated pretreatment EPID dose patterns were compared using criteria of 5% LPD, 1 mm DTA, or 2% of central axis pixel value with ≥95% of compared points required to pass for successful verification. Pretreatment field verification resulted in 97% percent of the points passing. ^ The RTPS and Monte Carlo phantom dose calculations were compared using 5% LPD, 2 mm DTA, or 2% of the maximum dose with ≥95% of compared points required passing for successful verification. RTPS calculation verification resulted in 97% percent of the points passing. ^ The measured and calculated EPID exit dose patterns were compared using criteria of 5% LPD, 1 mm DTA, or 2% of central axis pixel value with ≥95% of compared points required to pass for successful verification. Exit dose verification resulted in 97% percent of the points passing. ^ Each of the processes above verified an individual step in the treatment planning and delivery process. The combination of these verification steps ensures accurate treatment delivery to the patient. This work shows that Monte Carlo calculations and EPID dosimetry can be used to quantitatively verify IMSRT treatments resulting in improved patient care and, potentially, improved clinical outcome. ^

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The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity. ^

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Proper execution of mitosis requires the accurate segregation of replicated DNA into each daughter cell. The highly conserved mitotic kinase AIR-2/Aurora B is a dynamic protein that interacts with subsets of cofactors and substrates to coordinate chromosome segregation and cytokinesis in Caenorhabdiris elegans. To identify components of the AIR-2 regulatory pathway, a genome-wide RNAi-based screen for suppressors of air-2 temperature-sensitive mutant lethality was conducted. Here, I present evidence that two classes of suppressors identified in this screen are bona fide regulators of the AIR-2 kinase. The strongest suppressor cdc-48.3, encodes an Afg2/Spaf-related Cdc48-like AAA+ ATPase that regulates AIR-2 kinase activity and stability during C. elegans embryogenesis. Loss of CDC-48.3 suppresses the lethality of air-2 mutant embryos, marked by the restoration of the dynamic behavior of AIR-2 and rescue of chromosome segregation and cytokinesis defects. Loss of CDC-48.3 leads to mitotic delays and abnormal accumulation of AIR-2 during late telophase/mitotic exit. In addition, AIR-2 kinase activity is significantly upregulated from metaphase through mitotic exit in CDC-48.3 depleted embryos. Inhibition of the AIR-2 kinase is dependent on (1) a direct physical interaction between CDC-48.3 and AIR-2, and (2) CDC-48.3 ATPase activity. Importantly, the increase in AIR-2 kinase activity does not correlate with the stabilization of AIR-2 in late mitosis. Hence, CDC-48.3 is a bi-functional inhibitor of AIR-2 that is likely to act via distinct mechanisms. The second class of suppressors consists of psy-2/smk-1 and pph-4.1, which encode two components of the conserved PP4 phosphatase complex that is essential for spindle assembly, chromosome segregation, and overall mitotic progression. AIR-2 and its substrates are likely to be targets of this complex since mitotic AIR-2 kinase activity is significantly increased during mitosis when either PSY-2/SMK-1 or PPH-4.l is depleted. Altogether, this study demonstrates that during the C. elegans embryonic cell cycle, regulators including the CDC-48.3 ATPase and PP4 phosphatase complex interact with and control the kinase activity, targeting behavior and protein stability of the Aurora B kinase to ensure accurate and timely progression of mitosis. ^

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Purpose: Self-neglect (SN) is the inability to maintain self-care needs. It is thought that older adults who have impaired executive function (EF) develop the inability to do self-care and to protect themselves. The specific aims were to (1) determine the feasibility of using multiple EF measures with community-dwelling elders with SN, (2) identify changes in EF between baseline and 5-months in community-dwelling elders with SN who receive 50,000 IU or 400 IU of oral vitamin D monthly and (2) explore changes in specific dimensions of EF between the groups. ^ Methods: Fifty adults, 65 years of age and older, were recruited from Adult Protective Services with confirmed SN. A research nurse administered the following tests at baseline and five-months: Delis-Kaplan Card Sort Test (D-KEFS), Executive Interview (EXIT 25), CLOX Drawing Test (CLOX I, II), Trails Making Test A and B (TMT A & B) and the Mini-Mental State Examination (MMSE). Demographic data was collected at baseline and serum 25-OHD levels were collected at baseline and five-months. ^ Results: Older adults with SN were more likely to fail the CLOX1 and D-KEFS, while passing the MMSE, CLOX II, TMT A & B and the EXIT 25. At five-months, the only statistically significant difference between groups was in the TMT A & B test scores; the control group did better than the treatment group. There was a non-significant increase in serum vitamin D levels for both groups and no difference between groups. ^ Conclusions: Results from this study provide support that individuals who SN will complete a battery of EF tests and that they exhibit the following impairments consistent with executive dysfunction: 'concept generation', 'planning', 'inhibition', and 'spatial working memory'. Utilizing only one EF measure in individuals with intact cognition may result in unidentification of individuals with executive dysfunction, thus delaying necessary treatment. Future studies should attempt to determine different etiologies of executive dysfunction and determine if early treatment can prevent or reverse SN. ^ Key Words: Self-neglect, Executive Dysfunction, Executive Function, Adult Protective Services, Community-dwelling, Vitamin D ^

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La producción de aceite de oliva genera distintos subproductos entre los cuales el efluente o alpechín representa un serio problema mediambiental. En los países productores el alpechín es un residuo muy contaminante debido a su elevada composición orgánica, sus efectos inhibitorios y la tendencia de sus componentes a sufrir oxidación biológica. Estas características y la estacionalidad de su producción dificultan su eliminación. La industria del aceite de oliva está actualmente en expansión en Argentina. En Mendoza, dicha actividad tiene una gran tradición y un impacto ambiental considerable. El objetivo de este trabajo fue analizar los caracteres físico- químicos de los efluentes de fábricas de aceite oliva en Mendoza (Argentina) para conocer la realidad de la industria local y rever las especificaciones legales para efluentes. Los efluentes de dos fábricas fueron evaluados en tres puntos de muestreo: agua de entrada al proceso, salida de la fábrica y pileta de deposición final de los efluentes. Se analizó el contenido de iones, pH, conductividad eléctrica, DBO y DQO. Los resultados obtenidos permiten concluir que las características del efluente dependen del método de extracción utilizado y la eventual dilución con agua de lavado. La calidad del agua subterránea utilizada en el proceso no es un factor determinante para lograr un efluente fácilmente tratable. El problema medioambiental que se plantea es la producción de un efluente con alto contenido orgánico, salino y bajo pH, caracteres que impiden su vuelco en cursos de agua superficial o red de cloacas, por no cumplir con los requisitos indicados en la normativa vigente. Por lo tanto, las fábricas elaboradoras de aceite de oliva serán las encargadas de que dichos efluentes reciban un adecuado proceso de depuración que permita su eliminación o reutilización.