As shown in Figure 2(a), dextran transport was increased approximately twofold in the cell cultures incubated with the AC formulation. Figure 2 Effects of the AC kinase inhibitor Brefeldin A formulation on Gemcitabine synthesis endothelial paracellular flux. (a) Increase in dextran permeation induced by the AC formulation. One hour after the addition of oligodeoxynucleotides (ODN), atelocollagen (AC), or the AC formulation (AC + ODN) to the inner … Next, the paracellular transport of atelocollagen was analyzed and compared with those of BSA and dextran. Inhibitors,research,lifescience,medical Neither BSA nor dextran affected the TER value of the cells. Only very small amounts of BSA and dextran penetrated the cell sheet during

the 2-hour study period; on the other hand, much more atelocollagen passed through, even though the molecular weight of atelocollagen is 4-5 times higher than those of BSA and dextran (Figure 2(b)). An examination using BMVEC [27] was performed to determine whether the effect of the AC formulation was specific to HMVEC. As a result, we found that Inhibitors,research,lifescience,medical the TER value of the BMVEC was also reduced by the AC formulation (and only the AC formulation), as shown in Figure 3. BMVEC forms the blood-brain barrier (BBB), where intercellular sealing function is strictly maintained. These results showed that the AC formulation is able to affect the paracellular flux of endothelial barriers. Figure 3 Effects of the AC formulation on the TER of BMVEC. The bar represents TER as a percentage compared Inhibitors,research,lifescience,medical to the value observed at

the start of the experiment. TER Inhibitors,research,lifescience,medical was determined at 1 and 2 hours after treatment with ODN alone (ODN), atelocollagen alone (atelocollagen), … 3.2. Effects on Cell Morphology It is well known that increased endothelial permeability is associated with impaired intercellular contact [32–35]. We carried out an immunohistochemical analysis of the cells treated with the AC formulation to clarify how their intercellular sealing was affected. As shown in Figure 4(a), treatment with the AC formulation markedly reduced the degree of intercellular contact,

as Inhibitors,research,lifescience,medical shown by intercellular gap formation, actin stress fiber formation, cellular contraction, and a lack of VE-cadherin. Adequate expression of claudin-5, one of the key components of the endothelial barrier, was noted at the cell periphery. However, ZO-1 protein expression was absent from the intercellular gaps. On the contrary, Dacomitinib Western blotting revealed that treatment with the AC formulation did not affect the expression of these proteins (Figure 4(b)). Although the TER value remained low as long as the AC formulation was present in the culture medium, the treatment did not cause toxicity. The cells survived well for at least 24hrs, and both the TER and morphology of the cells could be recovered by removing the formulation (data not shown). No such morphological changes were induced by treatment with ODN or atelocollagen alone (Figure 4(a)). Figure 4 Effects of atelocollagen combined with ODN on intercellular formation.

41,42 Thus, improvements in neurocognitive performance may help these patients to plan more effective strategies to prevent, substance misuse. However, it should be noted that newer www.selleckchem.com/products/Calcitriol-(Rocaltrol).html antipsychotics also produce some adverse effects. Although data from atypical interventions in this field are limited to those from small, mostly uncontrolled studies, atypical antipsychotics are associated with a decrease in substance abuse in schizophrenic patients.8 These findings, however, may be explained by the feasibility of new antipsychotics having a normalizing effect on the signal detection capabilities Inhibitors,research,lifescience,medical of the mesocorticolimbic

reward circuitry. Finally, neuroleptic medication may contribute to dysphoria and anhedonia, which might, be a consequence of impaired dopamine function in the nucleus accumbens and play an important, role in regard to comorbidity Inhibitors,research,lifescience,medical with substance abuse disorders.16 As a consequence, it, is important to optimize

neuroleptic medication with regard to the subjective experience of the patient. Preliminary results43 suggest a window of D2 receptor occupancy between 60% and 70% to be optimal for the subjective experience of patients, which is clinically relevant, concerning medication compliance and quality of life. However, careful interpretation is recommended, as further research is needed in order to investigate the effects of antipsychotics on subjective wellbeing, as well as on craving for Inhibitors,research,lifescience,medical drugs. Overall integrated treatment models that address both

disorders have been found to increase retention and participation in treatment, reducing symptoms and substance use.4 Therefore, it will be necessary to provide care assessment methodologies in both systems, addiction clinics, and mental health clinics, which simultaneously Inhibitors,research,lifescience,medical address Inhibitors,research,lifescience,medical both schizophrenia and substance abuse disorders. Conclusion and future directions It has been determined that, schizophrenic patients with co-occurring substance misuse disorders are vulnerable to an increased risk of illness and injury, poorer outcomes in psychosis, and higher rates of presentation to inpatient and emergency services. Another tremendous problem involves the high occurrence of incarceration among persons with a diagnosis of schizophrenia, who abuse substances and lack Brefeldin_A stable housing. Even though the vulnerability of persons with schizophrenia to substance abuse has been emphasized, the BAY 87-2243? degree of risk and adverse consequences diversify across various studies. Gender-specific approaches stress that young male patients are associated with a greater risk for substance abuse. However, substance use difficulties among women with schizophrenia are often insufficiently identified. Thus, it represents a great challenge that women with comorbidity of substance abuse in many cases do not obtain adequate substance-abuse treatment, and genderspecific approaches should be incorporated into treatment strategics.

Binding of IGF-1 or IGF-2 or insulin to the http://www.selleckchem.com/products/BI6727-Volasertib.html IGF-1R α-subunit leads to autophosphorylation of β-subunit residues, which then act as docking site to insulin receptor substrates … INSULIN AND IGF RECEPTORS Insulin and IGF-1 bind their own receptors at physiological concentrations, but due to their high homology in the structure of their receptors

a hybrid receptor may also exist. This may give rise to multiple variations of homo- or heteroreceptor dimers: IR-A/IR-A, IR-B/IR-B, IGF-1R/IGF-1R, IGF-1R/IR-A, and IGF-1R/IR-B (Figure 1). Insulin binds with high affinity to the IR-A or to IR-B but has low affinity for IGF-1R, while insulin Inhibitors,research,lifescience,medical has little or no binding to the hybrid receptor. IGF-1 has high affinity for the IGF-1R and to the hybrid receptors. IGF-2 can bind to IR-A or to IGF-1R and also to the hybrid IGF-1R/IR-A. In addition only IGF-2 can bind to the IGF-2R; this interaction mediates the endocytosis and clearance of IGF-2 from the circulation.37 In general, ligand binding to the IR-A or to the IGF-1 receptor mediates the mitogenic signaling Inhibitors,research,lifescience,medical pathway (cell survival, growth, and proliferation), while ligand binding to IR-B activates metabolic signaling. Binding to the hybrid receptors, leading to mitogenic or metabolic signaling, is determined by Inhibitors,research,lifescience,medical the

IR isoform that formed the hybrid receptors (Figure 1). ANIMAL MODELS IGF-1, IGF-1R, AND CANCER To Inhibitors,research,lifescience,medical understand the relationship between T2D, obesity, and cancer risk, the effects of the insulin and IGF-1 signaling have been studied in animal models of cancer and cancer cell lines. These studies help determine the mechanisms involved. In mice, IGF-1 levels were reduced by caloric restriction treatment Inhibitors,research,lifescience,medical and led to a reduction in tumor growths8 In rodents with reduced circulating IGF-1 levels tumor growth and metastasis were reduced. Administration of IGF-1

ligand to these mice reversed the reduction in both tumor growth and metastases.39 in addition, in Noble rats (prostate carcinoma model), increased IGF-1 levels resulting from exposure to high levels of sex hormones led to progression from benign prostatic Brefeldin_A growth to adenocarcinoma of the prostate40 IGF-1 signaling appears to prevent apoptosis by up-regulating the expression of MDM2. This protein facilitates P53 inhibition41 IGF-1 induces redistribution of integrins, receptors that bind to components of the extracellular matrix and involve cell migration, thereby aiding in metastasis. Addition of IGF-1 to colon cancer cell lines caused re-localization of integrins which resulted in increased cell migration.42 Another cell motility feature, the lamellipodia, was found to be induced by IGF-1 in melanoma and neuroblastoma cancer cell lines.43 In order to understand the role of the IGF-1R in tumorigenesis, animal studies have investigated modulation of the IGF-1R.

This work was also Idelalisib supported in part by the Bowman Family Foundation partnership with the National Alliance for Research on Schizophrenia and Depression (NARSAD).
he detection of psychotic disorder in the prodromal

phases, coupled with specialized early interventions to method prevent transition to overt psychotic disorder, has become the subject of an increasing amount of research and debate.1-8 Although this issue is by no Inhibitors,research,lifescience,medical means new,9,10 it is only in the last few years that the outlines of a consensus, based on quantitative arguments, are becoming discernible. These will be discussed in this article, using data from several population-based investigations to illustrate the quantitative arguments. Is there a rationale for schizophrenia prevention in the first place? The answer to this question is evident. If there is a way to prevent an illness that usually has a poor prognosis and starts in young adulthood, every effort should be made Inhibitors,research,lifescience,medical to put preventive Inhibitors,research,lifescience,medical measures into place. Work originating in Germany, the Netherlands, Norway, and elsewhere has suggested that a delay of about 1 year between the onset of positive psychotic symptoms

and the initiation of treatment is not rare.11-13 From the patient’s point of view this contributes not only to severe social stagnation and decline,14,15 but also to severe mental suffering, thus providing a powerful rationale for prompt treatment immediately after the onset of the first Inhibitors,research,lifescience,medical psychotic episode. Another rationale

for rapidly commencing treatment is the possibility that the longer the duration of untreated psychosis (DUP), the less effective treatment will be in the long term.16,17 It is quite likely that part of the observed association between Inhibitors,research,lifescience,medical a longer DUP and neuropsychological deterioration is noncausal.18,19 However, the mere possibility that prolonged episodes of psychosis impact negatively on longer-term outcome justifies the need for increased vigilance on the part of the clinician to identify prodromal symptoms.20,21 However, the concept of screening and prevention Anacetrapib in schizophrenia hinges on schizophrenia somehow manifesting itself before the onset of the disease. Therefore, the rationale for schizophrenia prevention, in terms of feasibility needs to be demonstrated first. Evidence has come from two lines of research. The first focused more on the expression of nonpsychopathological vulnerability over the course of development, and the second more on the expression of subclinical psychotic phenomena proximal to illness onset (Figure 1). Figure 1. Prepsychotic expression of illness.

Despite advances in treating HCV, even with the optimal delivery of the current interferon-based regimen for HCV, only about 50% of treated patients with genotype 1/4 successfully clear the virus (Mauss et al.

2011). The success of the current treatment is multi-factorial and depends on a combination of several host, viral, and treatment factors. Inhibitors,research,lifescience,medical Viral Sorafenib Tosylate clinical trial factors consist of HCV genotype, pretreatment viral load, and presence of viral quasi-species (Timm and Roggendorf 2007). Host factors include presence of co-morbidities such as obesity, cirrhosis, ethnic background, gender, and age (Bondini and Younossi 2006; Chen et al. 2007; Neumann-Haefelin et al. 2007; Sharma et al. 2007). Finally, treatment-related factors affecting response Inhibitors,research,lifescience,medical include adequate duration of treatment, patient adherence and, importantly, optimal management of PEG-IFN and RBV-related side effects (Mulhall and Younossi 2005; Sharma et al. 2007). Consequently, there are two main areas of focus to develop future treatment regimens for HCV. One of them focuses on new therapeutics that can potentially

increase the rates for sustained virological response (SVR) by developing regimens that would include direct acting antiviral agents (DAA). The other, equally important area, is to optimize treatment regiments and reduce its side-effect profile. Despite diligent Inhibitors,research,lifescience,medical efforts by clinicians and clinical investigators, successful management of treatment-associated side effects remains

a substantial problem and contributes significantly to treatment discontinuation or dose reduction (10 and 35%, respectively) (Manns et al. 2001; Dan et al. 2006). research use depression disorder is one Inhibitors,research,lifescience,medical of the least tangible, and one of the most difficult IFN-related side effects to quantify in the treatment of HCV. IFN-α-induced depression is markedly similar to major depressive disorder (MDD) and may be manifested as depressed mood, irritability, emotional lability, agitation, fatigue, apathy, Inhibitors,research,lifescience,medical anhedonia, anorexia, psychomotor retardation, sleep disturbance, sexual dysfunction, memory impairment, and diminished ability to concentrate (Valentine et al. 1998). Due to the variability of the symptoms and lack of unification in their measurements, studies on IFN-α-induced depression also produce variable results with incidence rates ranging from 16 to 45% in patients receiving treatment (Fattovich et al. 1996; Hauser et al. 2002; Dieperink et al. 2003). The most common risk factors Cilengitide for IFN-α-induced depression are related either to treatment regimen itself (i.e., higher dose and longer duration of medication) (Capuron and Ravaud 1999; Hauser et al. 2002; Dieperink et al. 2003; Capuron and Miller 2004) or to intrinsic factors predisposing patients to the development of DSM-IV symptom criteria for MDD. The most common risk factor of latter kind is pre-existing psychiatric problems or previously diagnosed MDD.

While much of the basic research traditionally focused on “critical periods” of early development, attention has focused more recently on opportunities to selleck chemicals induce neuroplasticity in adulthood or during another critical period, the aging process. This the following site editorial will address different facets of neuroplasticity, the need for translational research to interpret neuroimaging Inhibitors,research,lifescience,medical data thought to reflect neuroplasticity in the human brain, and in what conditions and when in aging and in a disease process should interventions that induce

neuroplasticity be targeted. Strategies to induce neuroplasticity The papers in this issue cover aging, as well as depression, dementia, and stroke, and include a range of interventions,

including manipulations in behavior (physical and cognitive activity/exercise), physiological factors (caloric restriction, cholesterol1-4), pharmacologic treatments (AMPA receptors5), manipulation of magnetic fields and electrical activity Inhibitors,research,lifescience,medical (transcranial magnetic stimulation [TMS], magnetic seizure therapy [MST], and deep brain stimulation [DBS]6,7). Based on the data presented,6 the use of TMS alone or in combination with pharmacologic treatment has great promise in treating cognitive deficits post-stroke and in dementia. Interventions associated with neuroplasticity Inhibitors,research,lifescience,medical that merit further preclinical and human study and that would have widespread applicability across neuropsychiatry conditions include epigenetic manipulations (histone deacelylase inhibitors), estrogen, and addressing neuroinflammatory processes.7,8-10 While there is a considerable focus on lifestyle and environmental Inhibitors,research,lifescience,medical factors associated with enhancing neuroplasticity, there are also modifiable factors that inhibit neuroplasticity and should be a focus of investigation and treatment development, Inhibitors,research,lifescience,medical particularly stress.1-3 The important consideration of neurotransmitter interactions and the aging brain is discussed by Mora.3 Preclinical data demonstrate that regional

neurotransmitter interactions in functionally connected Carfilzomib systems (in this case, glutamate modulation of dopamine and GABA) may change as a function of age, particularly under conditions of stress. There are several important implications of this work. First, in the human brain, the modulation of glutamate in aging and neurodegenerative disease is not well understood, as glutamate has a role in the maintenance of cellular function, as well as cell death.11 Several glutamatergic transporters and receptors play a critical role in synaptic and dendritic plasticity.10 Secondly, the mechanism of action of psychotropic medications involves actions on the primary target, as well as on functionally linked neurotransmitters.

Reactions like

dissociative symptoms, panic-like response, extreme withdrawal, psychotic-like symptoms, and suicidality all raise red flags regarding the person’s vulnerability to developing PTSD.11 Why is PTSD suitable for prevention? PTSD is different from other psychiatric disorders, in that it has a very clear point of onset. In most cases, the traumatic event is also the point of onset of symptoms. The second unique feature of PTSD is that it is characterized by a failure of the normal response to disappear. The www.selleckchem.com/products/Dasatinib.html expected response after exposure to a traumatic event is to experience shock, horror fear, terror, grief, Inhibitors,research,lifescience,medical etc. This is a normal response to an abnormal situation. It becomes a disorder when this normal response continues

(according to DSM-IV, for more than a month). Moreover, as mentioned earlier, the vast majority (80% to 90%) experience spontaneous recovery from these symptoms, and hence, one way to conceptualize PTSD is Inhibitors,research,lifescience,medical as a disorder where there is a failure to recover (Figure 3). If PTSD is a failure to recover, then our obligation, as clinicians, to the patient is primum non nocere Inhibitors,research,lifescience,medical (“First, do no harm” ), ie, not to interfere with the potent spontaneous recovery process which usually takes place. It seems that what we do in this “window of opportunity,” in those “golden hours” – the first few hours after the exposure to the traumatic event – might have the potential to dramatically alter the trajectory of PTSD. Figure 3. Most people exposed to trauma do not develop post-traumatic stress disorder. Memory and PTSD We submit that the main feature of PTSD is the traumatic memory, which is clinically expressed by Inhibitors,research,lifescience,medical criterion B of the DSM-IV, namely that the traumatic

event is persistently re-experienced through recurrent and selleckchem Nilotinib intrusive distressing recollections and/or recurrent distressing dreams, acting or feeling as if the traumatic Inhibitors,research,lifescience,medical event were recurring (including dissociative flashback episodes) and intense psychological distress and physiological reactivity upon exposure to internal or external cues that symbolize or resemble an aspect of “the event.” Thus, AV-951 the core pathology of PTSD is the re-experiencing – the distressing recollections, flashbacks, nightmares, etc. One way to describe this is that patients with PTSD arc haunted by the memory of the event. For them, the past is always present; it is as if the clock has stopped, and they are constantly either reliving the experience, or fighting very hard not to be exposed to triggers which might set off a flashback. The avoidance, numbing, and increased arousal would then be secondary phenomena. One question would be regarding the consolidation of the traumatic event. Consolidation is the transition from unstable to stable memory, and the question is, if we could prevent this consolidation, whether or not it would be beneficial.

54 This suggests that TRPC1 may not be an obligatory and/or exclusive component of the SFR (similar findings were reported for TRPC3 (http://www.ncbi.nlm.nih.gov/gene/7222) 55 ). However, as with all knockout experiments, there is always the possibility of compensatory changes in expression of other genes. One way of assessing order Ibrutinib this would be to use acute

knockdown experiments, ideally involving tissue-specific drivers of protein expression. It would also be instructive to explore acute MEF responses that would be expected to precede the SFR in cardiac myocytes or tissue preparations of TRPC1− / −  mice. TRPC6: Mammalian TRPC6 was initially identified as a mechanosensitive ion channel by Spassova et al., 56 who found that overexpression of TRPC6 in human embryonic kidney cell line 293 (HEK293) cells induced ISAC,NS. However, a subsequent study by Gottlieb et al. 50 found that TRPC6 overexpression in CHO and COS cells had no significant effect. More recently, it has

been suggested that TRPC6 is not mechanosensitive, unless co-expressed with the angiotensin II type 1 (AT1) receptor. 45,47 Data, more directly relevant for cardiac mechanosensitivity, came from Dyachenko et al., 58 who used mouse ventricular myocytes, as opposed to heterologous expression systems. Their whole-cell patch clamp experiments identified a robust ISAC,NS in response to shear stimuli, which was inhibited by pore-blocking TRPC6 antibodies. TRPC6 knockout blunts

the SFR in wild-type murine models, while its genetic down-regulation or pharmacological block returns ‘hyper-responsive’ murine models of Duchenne muscular dystrophy back to normal SFR levels, 55 highlighting the potential clinical relevance of targeted TRPC6 manipulation. TRPC6 is among a small number of SAC candidates that is highly expressed in human heart homogenates. 48 In murine heart, TRPC6 appears to be localised to T-tubules. 58 In agreement with this observation, detubulation GSK-3 inhibits ISAC,NS in murine cardiomyocytes. 58 Interestingly, a recent paper has suggested that the localization of TRPC6 shows marked plasticity in response to sympathetic stimulation via α1A receptors, and that these channels can translocate from T-tubules to the sarcolemma. 59 Whether this occurs physiologically is unclear; however, pre-treatment with α1A-agonists might serve as a useful experimental intervention to facilitate single-channel recordings of TRPC6, and potentially other channels localised in T-tubules, in adult ventricular myocytes. Other TRP channels: Several other members of the TRP family are mechanosensitive and are expressed in the heart. The TRPC3 protein has been identified in rat ventricular myocytes, also located in T-tubules.

The EMG (electromyography) signals were recorded with a bandpass filter of 0.1–100 Hz online at a sampling rate of 600 Hz. MEG recordings The MEG signals were recorded as described elsewhere (e.g., Wasaka and Kakigi 2012), with a helmet-shaped 306-channel detector array (Vectorview; Eleka Neuromag Yo, Helsinki, Finland), which comprised 102 identical triple sensor elements. Each sensor element consisted of two orthogonal planar gradiometers and one magnetometer coupled

to a multi-SQUID (superconducting Inhibitors,research,lifescience,medical quantum interference device) and thus provided three independent measurements of the magnetic fields. The MEG signals were Inhibitors,research,lifescience,medical recorded at a 600 Hz sampling rate online with a bandpass filter of 0.1–300 Hz. Raw records for MEG, EMG signals, and trigger pulse signals were all stored continuously on the same computer for off-line analysis. Prior to the MEG recording, four head position indicator (HPI) coils were placed at specific sites on the scalp. To determine the exact location of the head with

respect to the MEG sensors, an electric current was fed to the HPI coil, and the resulting magnetic fields were measured with the MEG sensors. These procedures allowed for alignment of the individual head coordinate system with the MEG coordinate Inhibitors,research,lifescience,medical system. The location of the HPI coils with respect to the three anatomical landmarks (nasion and bilateral preauriculas) was also measured using Inhibitors,research,lifescience,medical a three-dimensional (3D) digitizer to align the coordinate systems of MEG with magnetic resonance (MR) images, obtained with a 3T MR selleck chemicals Tipifarnib imaging system (Allegra; Siemens, Erlangen, Germany). Analyses In the movement task, trials that generated artifacts due to corrective EMG activities before or during movement,

or trials that were initiated without an intertrial interval less than 5 sec, were removed following manual inspection on a trial-by-trial basis. Each data set of MEG Inhibitors,research,lifescience,medical and EMG signals was time locked to the trigger signal and averaged. The time window Brefeldin_A of the analysis was from 3000 msec before (−) to 3000 msec after (+) the onset of the trigger signal, and for MEG recordings the prestimulus period from −3000 to −2000 msec was used as the DC baseline. The number of trials used for the analysis averaged 86 (±5) across subjects. As recorded magnetic fields in each coil are a summation of those from temporally overlapping multiple source activities, a multiple source analysis method has been used to differentiate each source activity (Mauguière et al. 1997; Hari and Forss 1999; Inui et al. 2004; Wang et al. 2004; Jung et al. 2009). We adopt the modeling procedure implemented in BESA 5.

Worldwide, there is a need for continued wetland inventories as small water bodies have often been underemphasized, and many inventories are therefore unreliable [15, 22]. The use of remote sensing in fundamental temporary and permanent wetland ecology, moreover, is currently not widespread, but has a large potential. Some biologists claim that spatial scales of remote sensing and scales usually covered by ecological or evolutionary research do not match, thus creating a perception problem [8], limiting the use of remote sensing techniques in biological studies.The aim of this study is to http://www.selleckchem.com/products/AP24534.html indicate that elementary and relatively cheap imagery and basic remote sensing techniques can substantially improve the knowledge on characteristics of temporary and permanent wetlands. In this study isolated open water wetlands in the Cape region of the Western Cape were characterised from seven Landsat images using supervised classification methods. Classification results of the Landsat imagery were compared with those of an Envisat image. Ecologically relevant traits (surface area, distance, dynamics, total number, and fraction of temporary and permanent wetlands) were investigated and discussed within the scope of wetland ecology. The effectiveness as well as the limitations of this straightforward remote sensing study, as an addition to ecological research, were evaluated.2.?Materials and Methods2.1. Optical wetland detectionIsolated open water wetlands were classified from seven Landsat TM and ETM+ images acquired on 9 January 1987 (summer), 16 October 1990 (winter), 3 June 1999 (winter), 4 December 1999 (summer), 31 July 2000 (winter), 24 February 2001 (summer), and 3 June 2002 (winter). Images were downloaded from the Global Land Cover Facility (GLCF) website or purchased from the United States Geological Survey Organization (USGS). The study area is located in the Cape Region of the Western Cape Province, South Africa (within latitude 33�� 03�� to 33�� 52�� South and longitude 17�� 57�� to 19�� 05�� East). It has a Mediterranean climate, receives much of its rainfall in winter months, and has relatively dry summers [23].Ground truth data were collected for the larger (from 0.32 hectare onwards) wetlands in the area by field surveys in 2004 and 2005 and supplemented with information from topographical maps obtained from the South African Chief Directorate of Surveys and Mapping. Most of the vegetation of these larger water bodies was situated at the edges (personal observation). Band 4, which showed a strong contrast between water bodies and other land features, was used to define at least 25 training sites for each land cover type (fresh water, sea, mountains, two types of vegetation, city, and sand dunes).