We have previously shown that two consecutive substitutions leaded to consecutive nonsense mutations in the BMPR1A gene in our proband’s family (21). The severity of disease in this family seemed more pronounced than in many others with germline BMPR1A mutations, as two affected individuals developed colon cancer, and one had selleck chem gastric juvenile polyps, both of which are more common in JP patients with SMAD4 rather than BMPR1A mutations (22,23). Our case also contradicts previous studies in the sense that JPS is an autosomal dominant disorder, and inheritance of a single deleterious

allele is sufficient to cause the JP phenotype (21). Apart from their academic significance, genetic Inhibitors,research,lifescience,medical examinations are crucial in identifying children who are carriers but have no symptoms. In any case, a paradigm shift is indeed needed for autosomal dominantly inherited diseases such Inhibitors,research,lifescience,medical as JPS. Hamartomatous polyps are not benign lesions; thus, we need to provide more advanced carcinoma-prevention by endoscopy, invasive endoscopy, or

surgical methods which may give these patients the opportunity for a better quality life with a longer life-span. Acknowledgements We thank Professor Istvan Ember (Medical University of Pecs, Hungary) Inhibitors,research,lifescience,medical for tumor marker analysis, Professor Istvan Racz (Petz Aladár Teaching Hospital of Győr, Hungary) for performing capsule endoscopy, and James R. Howe (University of Iowa Carver College of Medicine, Iowa City, IA, USA) for the genetic testing. Disclosure: The authors declare no conflict of interest.
Esophageal cancer is diagnosed in about 400,000 patients each year worldwide, and its incidence is increasing Inhibitors,research,lifescience,medical (1), it is the sixth leading cause of death from cancer (2). In

selleck catalog Europe, while incidence of SCC has remained stable or declined during the past few decades, the incidence of esophageal adenocarcinoma has been rising. This increase has been more prominent in Northern Europe, notably in the United Kingdom and Ireland (3,4). The majority of the patients suffering from a cancer Inhibitors,research,lifescience,medical of the esophagus presents with symptoms of dysphagia and weight loss because of an obstructive tumor (5). Several management options have been developed to palliate malignant dysphagia. These include endoluminal stenting GSK-3 or surgery and external beam radiation, brachytherapy, chemotherapy, chemoradiotherapy, laser treatment, photodynamic therapy or ablation using injection of alcohol or chemotherapeutic agents (6-8). Placement of self-expanding metallic stents (SEMS) made up of an alloy, usually nitinol or stainless steel, and deployed using endoscopic or fluoroscopic techniques, is a newer method for relief of dysphagia in these patients (9). External beam radiotherapy (EBRT) is known to provide durable and effective relief of dysphagia. However, there is a time lag before symptomatic relief occurs, and up to 6 weeks are required for maximum benefit (8).

90 These and other studies suggest that p-tau is promising in distinguishing AD from frontotemporal dementia

(FTD), with sensitivity and specificity rates of 85% to 90%. 90,91 A combination of various p-tau subtypes did not provide improved results in distinguishing between the groups due to ceiling effects. P-tau may also be useful in distinguishing AD from idiopathic normal pressure hydrocephalus (iNPII). A study found similarly altered concentrations of t-tau and Aβ42 in both groups compared with controls, while p-taul81P was considerably higher in the AD group only.92 The sensitivity and specificity rates were Inhibitors,research,lifescience,medical higher than 85%. A Ponatinib order systematic review discusses what clinical benefit p-tau might offer. The high negative predictive Inhibitors,research,lifescience,medical value of p-tau of approximately 90% appears to be particularly significant. This means that normal values rule out the presence of AD with

almost 90% probability.93 In MCI subjects, high p-tau231P concentrations correlated with a decline in cognitive performance and conversion to AD.94 Similar results were established for ptaul81P.95 The three p-tau subtypes presented above were comparable in this respect.96 High p-tau231P Inhibitors,research,lifescience,medical concentrations at the initial examination also correlated with structural disease progression, measured as the rate of hippocampal atrophy in the course of the disease.97 A recent European multicenter trial on CSF p-tau231 in MCI subjects has shown that Inhibitors,research,lifescience,medical the results for p-tau in predicting AD in this risk group are indeed stable and consistent throughout multiple centers. In this study p-tau proved to be a powerful candidate predictor of AD in MCI subjects even in a very short mean selleck chemicals observation interval of only 1 to 2 years.98

This result is particularly promising regarding clinical use of p-tau by general practitioners or consultants in order to Inhibitors,research,lifescience,medical inform patients as early as possible. A Swedish 6-year study investigated the predictive value of the combined t-tau, Aβ42, and p-taul81P (defined as a ratio) for AD in a group of 137 MCI patients.99 AD was able to be predicted in the MCI subjects with a sensitivity of 95% and a specificity of approximately 85% , both with a combination of t-tau and Aβ42 and with a combination of t-tau and the ratio of Aβ42/p-tau181P.99This suggests that a useful combination of markers may optimize prediction in a more heterogenous MCI population over a longer observation period. The single assay methods have been modified by using the Luminex xMAP® Drug_discovery technology (Luminex Corp, Austin, TX) based on flow cytometry, which allows several parameters to be determined at the same time; the three biomarker candidates presented here can thus be measured at once using a relatively small volume of CSF. The first multicenter results are promising.100 Determination of these parameters is implemented both in the US and the European dementia networks. The first round-robin study is currently being conducted.

The AUC for Ceritinib separation along LV1 was 0.71, with moderate sensitivity (0.74) but poor specificity (0.60). The loading plot (Supplemental Figure S1) indicates

a number of peaks contribute to the separation. The score plot from the OSC-PLS analysis of the NOESY spectra shown in Figure 1 (d), shows an even better separation between the two patient cohorts, and the loading plot (Supplemental Figure S2) shows Inhibitors,research,lifescience,medical mostly lipid peaks. These results show promise for the future study of lipids. However, a major challenge in using NOESY to study lipids is that it cannot fully distinguish lipids with different fatty acid chains as they overlap. As a result, the following analysis will focus on CPMG spectra since they contain a larger number of peaks from identifiable and quantifiable metabolites. Figure 1 (a) The averaged Carr-Purcell-Meiboom-Gill (CPMG) spectra (bottom) for the HCC patients (blue dashed line, n=40) and HCV patients (red solid line n=22), along with the difference spectrum Inhibitors,research,lifescience,medical (top, black solid line). Major differences in metabolites are indicated … Considering the contribution to the loading plots from Inhibitors,research,lifescience,medical many low-lying and unidentified metabolite peaks, as well as noise, a more

targeted approach was also pursued. Individual peaks from 19 known metabolites (See Supplemental Information Table S1) were integrated and analyzed to reduce the contribution Inhibitors,research,lifescience,medical from chemical noise and to focus the analysis on known metabolite species so as to provide more mechanistic information. Initially, PCA analysis was performed on the 19 metabolites to see the data clustering.

The results are shown in Figure S3; as anticipated, clear separation of the two groups was not observed in the PCA results. A PLS-DA model was built based on these metabolite signals to investigate classification and discrimination. The cross-validated prediction result and ROC curve are shown in Figure S4. The two sample classes are somewhat separated by this model, but a number of Inhibitors,research,lifescience,medical misclassifications still exist. The area under curve (AUC) is 0.71. The model was further tested by MCCV, and the results of the classification confusion matrix are shown in Supplementary Table S2. The low sensitivity (54%) and specificity (58%) that result from the MCCV procedure indicate that the model is not very strong. However, this model is still better than the permutation result (these data are provided in Table S2 as the values GSK-3 in parentheses). The sensitivity and specificity of the permutation test are only 50% and 48%, respectively, which is essentially a random result, as anticipated. The sensitivity and specificity results for both the true model and permutation test from 200 iterations are also plotted (see Supplemental Information Figure S5). Although not very impressive there is still some separation, which indicates that the predictive model is better than a random one.

Our clinical world will be governed by information technology and mathematical predictions, whether an entire community, a hospital, or a single patient is involved. Genetics and genomics, analyzed by robust internet-based programs that will reside in a cyber-cloud, will become an integral part of our world and will govern our clinical decisions. Medical devices combined with imaging will continue to evolve and offer new therapeutic options. Combinations of a device and a drug eluted over the right time and in the right space through microchip mechanisms

will be developed. Robotic and remote catheterization technologies will continue to evolve and introduce Inhibitors,research,lifescience,medical precision into the manually operated world.31–33 Surgery will be completely transformed to become minimally invasive and robotically driven, eliminating the need for large incisions. Genetically oriented molecular

and cellular therapies Inhibitors,research,lifescience,medical will eventually beat cancer. As we reach the limit of our society to pay for medical care, cost sensitivity will remain a major factor Inhibitors,research,lifescience,medical in the development and wide availability of new devices and new therapeutics. Abbreviations: FDA Food and Drug Administration; IPC induced pluripotent cells; PCI Crenolanib clinical percutaneous coronary intervention; PTCA percutaneous transluminal coronary angioplasty; TAVR transarterial aortic valve replacement. Footnotes Conflict of interest: Dr Beyar is also Chairman of the Board of the Rambam Research Fund Inhibitors,research,lifescience,medical and is on the Board of BioRap of the Rappaport Family Research Institute on

Medical Research. He is also co-founder of Instent and Corindus (previously Navicath), a Technion-Rambam incubator company.
In vivo studies were conducted in order to evaluate whether the active antioxidant components of PJ are absorbed. Recent studies examined the bioavailability and metabolism of punicalagin in the rat as an animal model.5,6 Two groups of rats were studied. Inhibitors,research,lifescience,medical One group was fed for 37 days with standard rat diet (n = 5), and the second one with the same diet plus 6% punicalagin (n = 5). The daily intake of punicalagin ranged from 0.6 g to 1.2 g. Glucuronides of methyl ether derivatives of ellagic acid and punicalagin were detected in plasma. 6H-Dibenzo [b, d] pyran-6-one derivatives were Brefeldin_A also observed in the sellckchem plasma, especially during the last few weeks of the study. In urine, the metabolite urolithin was observed along with 6H-dibenzo [b, d] pyran-6-one derivatives, and they were present as aglycones or as glucuronides. It was concluded that since only 3%–6% of the ingested punicalagin was detected as such, or as metabolites in urine and feces, the majority of this ellagitannin has to be converted to undetectable metabolites or accumulated in non-analyzed tissues. Only traces of punicalagin metabolites were detected in liver or kidney.

6,7 However, while these designs demonstrate that drug-dependence disorders

are familial, they cannot distinguish between genetic and environmental contributions to this familiality. A demonstration of genetic contributions to these and other disorders requires other designs, prominently twin and adoption studies. Two adoption studies conducted by Cadoret et al8,9 showed that the only biological selleck products factor that was significantly associated with drug abuse in the proband was an alcohol problem in first-degree relatives. However, Tsuang et al,10 Inhibitors,research,lifescience,medical studying a sample of more than 3000 twin pairs, found a significantly greater pairwise concordance rate for monozygotic (MZ) than dizygotic (DZ) twins for abuse of marijuana, stimulants, cocaine, and for all drugs combined. Using twin pairs ascertained through the Virginia Twin Registry, Kendler et al examined concordance rates for drug use and dependence Inhibitors,research,lifescience,medical among more than 800 female-female pairs.11-13 Model

fitting showed that twin Inhibitors,research,lifescience,medical resemblance for liability to the use of cocaine, cannabis, hallucinogens, opioids, and sedatives was due to both genetic and family environmental factors. Liability to abuse or dependence on cocaine and cannabis was due only to genetic factors. In contrast, however, in another study by Kendler et al14 of the use and misuse of six classes of illicit drugs by nearly 1200 male-male twin pairs, model fitting revealed that one common genetic factor exerted a potent influence on risk for both substance use and misuse for all six substances. Inhibitors,research,lifescience,medical There was a modest effect on risk of substancespecific genetic free copy factors seen for substance use, but in contrast to other studies cited above, not for abuse or dependence. Inhibitors,research,lifescience,medical A single common shared environmental factor was also found to exert an effect on risk of substance use, and to a lesser extent, on risk of abuse dependence. Despite some contradictory findings, overall, the data from adoption, twin, and family studies support a substantial

genetic contribution to drug dependence, including the existence of genetic factors specific to each of these disorders, and factors common to these disorders and other forms of substance dependence. It is only common genetic factors (that is, those that influence more than one substance) that are likely to be important worldwide (genetic Carfilzomib factors specific to substances will vary because the specific substances vary). Whether genes relevant to drugs of abuse that have some similarities in their mechanisms of action, such as cocaine (important, eg, in the US) and methamphetamine (predominant, eg, in Thailand, and important in certain regions in the US) will prove to overlap, is still an open question. Further, different risk factors may be important in different populations (discussed in ref 1).

Excitatory synapses between pyramidal cells, and from pyramidal cells to the class of inhibitory interneurons activating chloride currents, were modified according to a Hebbian learning rule. When a spike arrived along a presynaptic axon, the maximal conductance of the synaptic current was changed in proportion to the amount by which the average of the postsynaptic membrane potential exceeded a modification threshold. Further Inhibitors,research,lifescience,medical methodological details are explained in the legend of Figure 6 below. Figure 6. Activity

in a network biophysical simulation showing the significance of long-term potentiation (LTP) of recurrent inhibition for recall of stored input patterns. This figure illustrates activity during recall. Activity during learning is Inhibitors,research,lifescience,medical not shown. A. … In order to examine the effects of age and hormonal status on recurrent inhibition, in vitro experiments similar to those described above were conducted on a cohort of rats aged 6 to 9 months or older. The examined groups of Long-Evans rats consisted of “younger”

females aged 200 days, ovariectomized females aged 200 days, “older” females aged 380 days, and males aged 250 Inhibitors,research,lifescience,medical days. One hemisphere of each brain was used for electrophysiological studies while the contralateral one was processed for immunohistochemistry. Elevated levels of the endogenous partial NMDA truly antagonist N-acetyl-L-aspartyl-L-glutamic acid (NAAG) are one of the striking findings in postmortem brains of schizophrenic patients.14 To mimic this condition and to characterize the effect of chronic low-dose NMDA antagonist exposure during puberty, we injected MK-801 Inhibitors,research,lifescience,medical (0.02 mg/kg body weight) intraperitoneally in 52-day-old rats for 2 weeks (MK-801: n=6; saline controls: n=6) before harvesting the hippocampi. During this period, rats showed no abnormalities of behavior or neurological signs of acute intoxication. Whole-cell patch clamp recordings Inhibitors,research,lifescience,medical were performed from CA1 principal neurons 3 days after the last injection.

In addition, a relative cell Anacetrapib count was performed on 15- µm cryostat slices triple-stained with antiparvalbumin, anticalretinin, and DAPI, as markers for the interncuronal subpopulation and total cell number, respectively, on the hippocampus not used for electrophysiology. Results The impact of acute NMDA antagonist application on the generation of IPSPs Whole-cell patch clamp recordings were obtained from pyramidal CA1 cells, manually held at -60 mV, and the IPSP inhibitor Baricitinib amplitude in response to low frequency (0.05 Hz, 0.5 -1 mA, 400 ms) was measured. Under drug-free baseline conditions, the mean amplitude of the IPSP was 6.7 ±0.5 mV (mean±SE). All NMDA antagonists tested, both competitive and noncompetitive, decreased the IPSP amplitude in a dose-dependent manner.

According to clinical observations,

6 hours suffice for normal tissues with the exception of spinal cord, for which a dose below 4000 cGy is recommended in hyperfractionated accelerated RT. The maximum point dose received by the spinal cord in our study was 4110 cGy, with 10 patients receiving doses above 4000 cGy. Of these 10 patients, 5 died, and the median duration of follow up in the remaining 5 patients is 15 months (9-23 months). No patients in the study had L’Hermitte’s syndrome Inhibitors,research,lifescience,medical or myelitis. No cardiac toxicity occurred in 19 of our study subjects (95%). In only one currently patient (5%), pericardial effusion developed approximately 1.5 months after the treatment. DVH examination showed that the radiation dose received by the entire cardiac volume Inhibitors,research,lifescience,medical was 308 cGy. In the study by Ishikura et al. (20), 78 patients with esophageal cancer received concomitant CRT (6000 cGy plus brachytherapy) and 8 patients (10%) had Grade III pericarditis, 3 patients (4%) had radiation pneumonia, and 4 patients (5%) had esophageal strictures. In the study by Yamada et al. (21) where concomitant CRT (5500-6600 cGy with brachytherapy) was given to 63 patients with T1 N0 esophageal cancer, late toxicities included pericardial effusion in 3 cases,

and esophageal fistula (Grade IV and V) in 2 cases. Three-dimensional conformal RT, intensity-adjusted RT and proton treatment as well as Inhibitors,research,lifescience,medical avoidance from pre-load areas are recommended to avoid from cardiac side effects. In this study, Inhibitors,research,lifescience,medical four patients died due to gastrointestinal bleeding, which was probably due to esophageal perforation resulting from tumor necrosis. An additional five patients had grade III esophageal toxicity. A higher than expected rate of esophageal toxicity observed in this study may be due to the high radiation Inhibitors,research,lifescience,medical dose used. In addition, hyperfractionated dosing may not allow appropriate tissue repairing. In one patient, PET-CT showed metabolic complete response, but the patient died at week 5 before undergoing surgery. Early thorax computerized tomography images following

chemoradiotherapy did not allow an accurate distinction between edematous and tumor tissues due to Batimastat acute side effects. We believe that if surgery can be accomplished in patients with clinical response, it may be possible to minimize deaths due to esophageal perforation. Conclusions Improved radiation dose schedules and achievement of maximum possible pCR rates may improve survival and organ protection in patients with esophageal cancer. In these patients, HART may help to target local disease control and increased survival. However, several factors including the performance status, treatment compliance, and tumor dimensions also play an important role in patient selection. Further studies to improve neoadjuvant and radical chemoradiotherapy dose schedules are warranted for maximum local control rates with minimal toxicity. In particular, high esophageal toxicity should be addressed.

119 Moreover, this study determined that several miR-21 mRNA targets were differentially expressed purchase Capecitabine during fibrogenic EMT of EMCs, such as PDCD4 and SPRY1, of which miR-21-dependent suppression contributed to the development of the fibroblast-like phenotype of EMCs. 119 Another study of the same group utilized TGF beta-induced EMT in rat-derived adult EMC cultures to investigate the role of Islet-1 (Isl1), a known marker of progenitor cells such as EMCs. They reported that Isl1

promoted the mesenchymal phenotype in untreated EMCs, whilst during TGF beta-induced EMT Isl1 was underexpressed, exerting a negative effect on EMT progression. The observed underexpression of Isl1 was in part attributable to miR-31, which was shown to act as a negative modulator of cardiac fibrogenic EMT, primarily via targeting Isl1. 120 Overall, these studies shed light to molecular mechanisms implicated in the contribution of EMCs to cardiac fibrosis, whilst suggesting a regulatory role for miR-21 and miR-31 in the fibrogenic EMT of EMCs. According to recent studies, endothelial cells can also provide fibroblast-like cells through endothelial-to–mesenchymal transition (EndMT), but the presence of cells of this origin in the adult myocardium occurs only under pathological conditions and is associated with fibrosis. 121 Zeisberg and partners suggested that endothelial cells may undergo (EndMT) and generate CFs, and they

showed that EndMT contributes to cardiac fibrosis progression in mouse models of pressure overload and chronic allograft rejection. 122 More recently, Ghosh et al reported differential expression of several miRs during cardiac EndMT. 123 Specifically, they treated cultured mouse cardiac endothelial cells (MCECs) with TGFbeta2 to trigger EndMT, and performed microRNA microarrays to measure total microRNA expression

in fibroblast-like cells vs MCECs. They reported significant expression changes in a range of miRs in fibroblast-like cells, and amongst them there were many previously associated with CVD ( ↑ miR-125b, -21, -30b,-195, Let-7c, -7g; ↓ miR-122a, -127, -196, -375). The expression of miR-125b was further validated by qPCR, whilst the protein levels of its target p53 were found downregulated in the EndMT-derived fibroblast-like cells. Interestingly, p53 is known to antagonize TGFbeta-induced profibrotic responses, 124 therefore miR-125b overexpression may lead to profibrotic signaling Cilengitide upregulation via suppressing its target p53 in these fibroblast-like cells. In conclusion, EndMT-derived fibroblast-like cells emerge as a novel cardiac fibrosis mediators, whilst their disease-specific existence in the adult myocardium may facilitate the development of miRNA based tools to target fibrosis. miRNAs impact on calcium cycling The dysregulation of miR-1 and -133a appears to serve multiple and distinct roles during HF development and progression.

The gender difference was opposite in a computer-pointing task (Rohr 2006), with motor times shorter in men, favoring speed, than women, highlighting accuracy. In the present study, fairly comparable results were obtained for human subjects and monkeys, as far as the hand Ivacaftor side effects dominance is concerned. Indeed, 62% of monkeys and 55% of human subjects did not show any statistically significant Inhibitors,research,lifescience,medical hand dominance, as assessed by the score derived from the

modified Brinkman board task. Concerning the CTs, the results are more difficult to interpret in monkeys. The CTs were fully coherent with the score in one case only (Mk-CA), whereas for the other monkeys, there was no, or less, consistency (Table ​(Table1).1). As reminder, the CT is a parameter Inhibitors,research,lifescience,medical additional to the score, which eliminates possible biases in the score, due to inattention and/or lack of motivation of the monkey. In other words, it does not take into account the time interval between two slot manipulations. Moreover, we had taken into consideration only the last 20 both sessions at plateau, to focus on the supposedly most stable daily behavioral sessions. It may, however, be interesting to consider the CT in more sessions Inhibitors,research,lifescience,medical in the plateau phase for a stricter comparison with the score for the very same sessions, although, in previous studies

(e.g., Kaeser et al. 2010, 2011), the CTs were largely stable during the entire plateau phase. The discrepancy between score and CTs is likely to be due to other parameters, such as diverted Inhibitors,research,lifescience,medical attention in between the grasping of two consecutive pellets. It may also originate from the different motor habits reflected by the temporal sequence followed by the animal to visit the slots (e.g., the monkey scans the board systematically from one side to the other or from the middle and then to the sides; see Kaeser et al. 2013). Moreover, at a given time point, the animal may change prehension strategy (e.g., collect two pellets at a

time). As long as the new strategy is not fully mastered, the hand dominance may vary, although the CTs Inhibitors,research,lifescience,medical remain short. In human subjects, as for the score data, the CT data showed that the hand dominance is generally consistent with the hand preference. The present study offers the opportunity to compare the hand dominance and the hand preference for both human subjects Carfilzomib and nonhuman primates. As reminder, the human subjects exhibiting hand dominance showed, most of the time, the same laterality for hand preference. This was not the case for the monkeys, where the laterality of the hand dominance did not systematically correspond to the one of the hand preference (Table ​(Table1).1). The same conclusion was met in a study conducted on four female M. fuscata Japanese monkeys (Kinoshita 1998). Concerning the hand preference, the results in human subjects are very consistent with their self-assessment.

Finally, in Section 5 some conclusions are provided.2.?Nonlinear Static Decoupling2.1. Coupling Error Model and NotationsWe first establish an appropriate coupling error model to capture the relationships between input forces and corresponding coupling errors. In the model, the input forces and output voltages of a 3-axis force sensor in X, Y, Z directions are defined as fx, fy, fz and ux, uy, uz, respectively.For each dimension, output voltages are partitioned into two categories. One category includes the voltages corresponding to input forces in the same dimension, called prime voltages. The other category includes the voltages corresponding to the input forces in the other two dimensions, called coupling errors. We use uxx, uyy, uzz to denote prime voltages and ex, ey, ez to denote coupling errors in X, Y, Z directions, respectively. Prime voltages account for the majority of output voltages. Next, coupling errors are separated into two coupling error elements caused by input forces of different dimensions. Let (exy, exz) represent the coupling error element in X direction, where exy refers to the coupling error element caused by fy, and exz refers to the coupling error element caused by fz. Similarly, we split the coupling error in Y direction into eyx and eyz, and split the coupling error in Z direction into ezx and ezy. We can get:{ux=uxx+exy+exzuy=uyy+eyx+eyzuz=uzz+ezx+ezy(1)Based on the observation of calibration data of multi-axis force sensors in our lab, we make the following scientific research assumptions about coupling errors.The relationship between the prime force and the prime voltage in every dimension is linear;Relationships between disturbing force and thei
Many applications based on vehicle localization, such as navigation systems, fleet management or Electronic Toll Collection (ETC), are a reality today thanks to the so-called Global Navigation Satellite Systems (GNSS) and digital maps. GNSS devices are exploited to estimate the vehicle location, while digital maps are used to refer this location to the road segments where the vehicle drives.However, location-based applications must face serious drawbacks in urban environments, where perhaps safety systems and location-based services become of more necessity. Main drawbacks can be summarized as follows:In urban built-up areas, the satellite signals used by GNSS sensors to estimate the vehicle location are strongly affected by the environment. GNSS signals are reflected, dispersed and attenuated by buildings, other vehicles, trees, etc. [1].While in highways and interurban areas the road layout trends to be simple and the most common approach to define the road shape based on polylines works well [2], in cities the road layout is far more complex and the polylines lack the necessary flexibility to accurately define the road shape.