After the pars flaccida of the tympanic membranes were completely

After the pars flaccida of the tympanic membranes were completely removed from male gerbils, corresponding portions of tympanic membranes of female gerbils were transplanted to the area of defect, and then we ligated the EAC (hybrid-model group). As a control group, the EAC of normal male and female gerbils was ligated without myringoplasty. In all ears of each group, the induced cholesteatomas were seen. In situ PCR

was then performed to detect the mouse X chromosome-linked phosphoglycerate kinase-1 (pgk-1) gene on the paraffin sections. One pgk-1 spot in the epithelial nuclei was detected in male cholesteatoma, and MI-503 molecular weight two pgk-1 spots were detected in female cholesteatoma, respectively. On the other hand, in the hybrid-model group, we detected not only one but also two pgk-1 spots in the epithelial nuclei of cholesteatoma. These results strengthened the evidence that the origin of epithelial cells in cholesteatoma Liproxstatin1 is the tympanic membrane in this model, but not the residential middie ear epithelial cells or the skin of the EAC. (Am J Pathol 2010, 176:2602-2606; DOI: 10.2353/ajpath.2010.091182)”
“Cytochrome P450 aromatase (CYP19) catalyzes conversion of testosterone

to estrogen, and is thought to influence neural and reproductive development in vertebrates. Unlike higher vertebrates, many teleost fish, including the medaka (Oryzias latipes) have two aromatase genes, one expressed predominantly in the ovary (cyp19a) and the other in the brain (cyp19b). However, the exact roles of the two aromatase genes see more in neural or ovarian development in fish are unclear. The primary objective of this study was to determine the pattern of 432 expression of each of the genes in developing and

adult medaka. Real-time PCR analysis indicated that both isoforms are expressed in adult ovary and brain, with predominant expression of cyp19a in the ovary and cyp19b in the brain. cyp19a was expressed at significantly higher levels in ovaries than in testes, whereas cyp19b was expressed at higher levels in the adult brain of females than males. Ontogenic expression showed that neither of the aromatase transcripts is inherited maternally, with onset of zygotic expression of both isoforms Occurring just prior to hatching (stage 39). Also the expression of the ovarian, but not the brain, isoform was significantly higher in genetically female individuals than in males of similar developmental stage. This coincided with the known increased proliferation of germ cells in XX genotypes, suggesting a possible role for cyp19a in ovarian differentiation. Differential expression of both isoforms in adults and during early larval development suggests that the genes have distinctly different roles: cyp19a contributing predominantly to ovarian differentiation and development; and cyp19b contributing towards neural development and perhaps sexual behavior in adults. Crown Copyright (C) 2008 Elsevier Inc.

In general, systemic maternal exposure increased proportionally w

In general, systemic maternal exposure increased proportionally with dosage in rats, but less than proportionally https://www.selleckchem.com/products/AC-220.html in rabbits. In conclusion, the no-observed adverse effect levels following

LY500307 administration were 1 mg/kg/day for male rat fertility, 0.3 mg/kg/day for female rat fertility and EFD, and 25 mg/kg/day for rabbit EFD. Adverse reproductive and developmental effects only occurred at or above parentally toxic dosage levels and were considered predominantly due to off-target ER effects.”
“As the longevity of patients with congenital heart disease improves, the number surviving to adulthood will continue to rise. Consequently, practicing physicians can expect to encounter an increasing number of adult patients with various congenital cardiac conditions. Impaired exercise tolerance in this patient population is exceptionally common; adult www.selleckchem.com/PARP.html patients with congenital heart disease have reduced exercise capacity compared with healthy, age-matched

counterparts. The different methods of evaluating exercise capacity, the characteristic physiologic 4 abnormalities encountered in patients with various congenital cardiac conditions, the pathophysiologic mechanisms that may account for these abnormalities, and the clinical implications of these findings are discussed.”
“Riparian systems are prone to invasion by alien plant species. The spread of invasive riparian plants may be facilitated by hydrochory, the transport of seeds by water, but while ecological studies have highlighted the possible role of upstream source populations in the establishment and persistence of stands of invasive riparian plant species, population genetic PXD101 chemical structure studies have as yet not fully addressed the potential role of hydrochoric dispersal in such systems.\n\nA population genetics approach based on a replicated bifurcate sampling design is used to test hypotheses consistent with patterns of unidirectional, linear gene flow expected under hydrochoric dispersal of the invasive

riparian plant Impatiens glandulifera in two contrasting river systems.\n\nA significant increase in levels of genetic diversity downstream was observed, consistent with the accumulation of propagules from upstream source populations, and strong evidence was found for organization of this diversity between different tributaries, reflecting the dendritic organization of the river systems studied.\n\nThese findings indicate that hydrochory, rather than anthropogenic dispersal, is primarily responsible for the spread of I. glandulifera in these river systems, and this is relevant to potential approaches to the control of invasive riparian plant species.”
“Obstructive sleep apnea (OSA) and hypertension are closely linked conditions. Disordered breathing events in OSA are characterized by increasing efforts against an occluded airway while asleep, resulting in a marked sympathetic response.

A549 cell pretreatment with WRW4, an antagonist of the transmembr

A549 cell pretreatment with WRW4, an antagonist of the transmembrane formyl peptide receptor-like 1 protein attenuated LL-37′s ability to increase cell stiffness. The LL-37-mediated increase in cell stiffness was accompanied by a decrease in permeability and P. aeruginosa uptake by a confluent monolayer of polarized normal human bronchial epithelial cells. These results suggested that the antibacterial effect of LL-37 involves an LL-37-dependent increase in cell stiffness

that prevents epithelial invasion by bacteria. The this website Journal of Immunology, 2011, 187: 6402-6409.”
“Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a gradual loss of motoneurons. The majority of ALS cases are associated with a sporadic form whose etiology is unknown. Several pieces of evidence favor autoimmunity as a potential contributor to sporadic ALS pathology. To gain understanding concerning possible antigens interacting with IgGs from sporadic ALS patients (ALS-IgGs), we studied immunoreactivity against neuromuscular junction (NMJ), spinal cord and cerebellum of mice with and without the Ca(V)2.1 pore-forming subunit see more of the P/Q-type voltage-gated 3 calcium (Ca(2+)) channel. ALS-IgGs showed a strong reactivity against

NMJs of wild-type diaphragms. ALS-IgGs also increased muscle miniature end-plate potential frequency, suggesting a functional role for ALS-IgGs on synaptic signaling. In support, in mice lacking the Ca(V)2.1 subunit ALS-IgGs showed significantly reduced NMJ immunoreactivity and did not alter spontaneous acetylcholine release. This difference in reactivity was absent when comparing N-type Ca(2+) channel wild-type or null mice. These results are particularly relevant because motoneurons are known to be early pathogenic targets in ALS. Our findings add further evidence supporting autoimmunity as one of the possible mechanisms contributing to ALS pathology. They also suggest that serum autoantibodies in a subset of ALS patients would find protocol interact with NMJ proteins down-regulated when P/Q-type

channels are absent.”
“Recycling of poly(ethyleneterephthalate) waste was achieved through glycolysis using diethyleneglycol (DEG) and poly(ethyleneglycol) (PEG 400), which yielded different fractions that exhibited hydroxyl numbers of 174.41 and 54.86 mg of KOH/g, respectively, whereas GPC profiles revealed bimodality in both cases corresponding to Mn values equivalent to 534 and 1648. The products of glycolysis from both cases were individually incorporated as modifiers during the synthesis of urea-formaldehyde resins from both the basic as well as acidic stages, respectively. It was found that the free formaldehyde level was remarkably decreased for the modified resins while the gel time was slightly affected indicating some activation of the resins.

Conclusion: More

than material factors, psychosocial fact

Conclusion: More

than material factors, psychosocial factors, mastery and self-efficacy in particular, explained a large part of the educational differences in physical and mental functioning in older people. Further research is recommended to explore the amenability to change of characteristics that hamper people from taking control over their lives.”
“Traditionally, IBD diagnosis is based on clinical, radiological, endoscopic, and histological criteria. Biomarkers are 123 needed in cases of uncertain diagnosis, or to predict disease course and therapeutic response. No guideline recommends the detection of antibodies (including ASCA and ANCA) for diagnosis or prognosis selleck of IBD to date. However, many recent data suggest the potential role of new serological markers (anti-glycan (ACCA, ALCA, AMCA, anti-L and anti-C), anti-GP2 and anti-GM-CSF Ab). This review focuses on clinical utility of these new serological markers in diagnosis, prognosis and therapeutic monitoring of IBD. Literature review of anti-glycan, anti-GP2

and anti-GM-CSFAb and their impact on diagnosis, prognosis and prediction of therapeutic response was performed in PubMed/MEDLINE up to June 2014. Anti-glycan, anti-GP2 and anti-GM-CSF Abate especially associated with CD and seem to be correlated with complicated find more disease phenotypes even if results differ between studies. Although anti-glycan Ab and anti-GP2 Ab have low sensitivity in diagnosis of IBD, they could identify a small number of CD patients not detected by other tests such as ASCA. Anti-glycan Abs are associated with a progression to a more severe disease course and a higher risk for IBD-related surgery.

Anti-GP2 Ab could particularly contribute to better stratify cases of pouchitis. Anti-GM-CSF Ab seems to be correlated with disease activity and could help predict relapses. These new promising biomarkers could particularly be useful in stratification of patients according to disease GDC-0973 ic50 phenotype and risk of complications. They could be a valuable aid in prediction of disease course and therapeutic response but more prospective studies are needed. (C) 2014 Elsevier B.V. All rights reserved.”
“Previous research evaluating the use of adjuvant endocrine therapy among postmenopausal breast cancer patients showed with 15-50% wide ranges of non-adherence rates. We evaluated this issue by analysing an unselected study group comprising of 325 postmenopausal women, diagnosed from 1997 to 2003 with hormonal receptor-positive invasive breast cancer. The different clinical situations that led to the discontinuation of adjuvant endocrine therapy were clearly defined and differentiated: non-adherence was not simply the act of stopping medication, but rather the manifestation of an intentional behaviour of the patient. Of the 287 patients who initiated endocrine therapy, 191 (66.6%) fully completed this treatment. Thirty-one patients (10.

014) Plexin-A3 decreased significantly with progression towards

014). Plexin-A3 decreased significantly with progression towards invasive cancer (P < 0.045), whereas Plexin-A1 expression was only significantly reduced once invasion had occurred (P = 0.012). Np1 and Np2 were expressed in both endothelial and epithelial/tumour cells. Np2 expression did not change, but Np1 expression significantly increased in the spectrum from hyperplasia to ductal carcinoma in situ (P < 0.035), but decreased with invasive cancer.\n\nConclusion: These data suggest that a decrease in class 3 semaphorin and their plexin receptors have some relationship with disease progression

in ductal breast carcinoma.”
“In this study, CaCu3Ti4O12 (CCTO) ceramics were doped with cesium and cerium atoms to possibly improve the electrical properties of these widely used ceramics. PFTα in vivo In all cases, pure phase perovskites were produced where cesium doping enhanced the grain growth and cerium doping produced grain growth inhibition. The cesium doping showed an improvement in loss tangent performance, in contrast

to the cerium doping which showed a negative result. A high dielectric constant >15,000 with a dielectric loss lower than 0.06 was observed for cesium 2.0 mol% doped at high frequencies. These results were related to the change in microstructure and the properties of grain boundary after doping. check details selleck inhibitor (C) 2011 Elsevier Ltd and Techna Group S.r.l. All rights reserved.”
“In this work, atmospheric pressure photoionization was investigated for use in characterizing protein palmitoylation, which is a major post-translational modification of membrane proteins. The study focused on native and palmitoylated peptides originating from plasma membrane proteolipids, such as tetraspanins CD9 and CD151. Mass spectrometry experiments were performed using

synchrotron radiation as a tunable UV source that provides optimal energy for photoionization (SR-APPI). In the positive ion mode, intense fragment ions corresponding to a. 6, candy ions were observed. Interestingly, these fragment ions conserved the palmitoyl modification, thus allowing for unambiguous structural characterization of the palmitoylated peptides. In-source fragmentation under APPI conditions offers a unique complement to conventional methods such as MS/MS, and the results demonstrate that APPI is a versatile and promising technique for the in-source characterization of post-translational modifications and top-down proteomics of membrane proteins. (C) 2012 Elsevier B.V. All rights reserved.”
“Background: The goal of this study was to determine the application of health belief model in oral health education for 12-year-old children and its effect on oral health behaviors and indexes.

Therefore, we hypothesized that acetylation and/or methylation of

Therefore, we hypothesized that acetylation and/or methylation of histone H3 may underlie sexual differentiation, at least in some regions of the brain. We measured levels of acetylated (H3K9/14Ac)

and trim-ethylated (H3K9Me3) H3 in whole neonatal mouse brains and in three regions: preoptic area + hypothalamus, amygdala and cortex + hippocampus (CTX/HIP). Sex differences in H3K9/14Ac and H3K9Me3 (males > females) were noted in Selleck Sonidegib the CTX/HIP on embryonic day 18, the day of birth, and six days later. To determine if T mediates these changes in H3 modifications, pregnant dams received vehicle or T for the final four days of gestation; pup brains were collected at birth. Methylation of H3 was sexually dimorphic despite hormone treatment. In contrast, H3 acetylation in the CTX/HIP of females from T-treated dams rose to levels equivalent to males. Thus, H3 modifications are sexually dimorphic in the developing mouse CTX/HIP and acetylation, but not methylation, is masculinized in females by T in utero. This is the first demonstration that histone modification is associated with neural sexual differentiation.”
“Alkaline fuel cell membranes have the potential to reduce the cost and LCL161 clinical trial weight of

current fuel cell technology, but they still have not been broadly commercialized due to poor hydroxide conductivities and mechanical properties, in addition to low chemical stability. One approach to address these mechanical and transport shortcomings is forming a morphologically bicontinuous network of an ion transporting phase and a hydrophobic phase to provide mechanical strength. In this report, membranes having bicontinuous morphologies are fabricated by cross-linking

cation-containing block copolymers with hydrophobic constituents. This is accomplished in a single step and does not require postpolymerization modification. The resulting materials conduct hydroxide ions very rapidly, as high as 120 mS cm(-1) in liquid water at 60 degrees C. The methodological changes required to obtain a bicontinuous Buparlisib morphology from such 432 strongly self-segregating block copolymers, relevant to other applications in which bicontinuous structures are desired, are also described.”
“The hydroalcoholic extract of fruits of Ziziphus jujuba (ZJ) was investigated for its anti-inflammatory effect using acute and chronic models of inflammation in rat. Wistar albino rats of either sex were employed in the present study (n = 6). Acute inflammation was induced by subplantar administration of carrageenan (1%) in rat hind paw. Chronic inflammation was induced by interscapular implantation of a sterile cotton pellet (50 mg). ZJ extract as test drug and indomethacin (10 mg/kg) as standard were used. Serum nitrite/nitrate was also estimated to determine the expression of nitric oxide. In the acute study, carrageenan (1%) administration caused marked paw edema.

This selectivity was more robust when 123

This selectivity was more robust when larger numbers of surrounding items and multiple features were included in the display, and it was absent when only a few items were presented immediately outside the CRF. In addition, the popout modulation

of V4 activity was eliminated when top-down attention was directed to locations outside of the CRFs during saccade preparation, indicating that the salience of popout stimuli is not sufficient Ro-3306 Cell Cycle inhibitor to drive selection by V4 neurons. These results demonstrate that neurons in feature-selective cortex are influenced by bottom-up attention, but that this influence is limited by top-down attention.”
“Whether uni- or bilateral drainage should be performed for malignant hilar biliary obstruction remains a matter of debate. Moreover, endoscopic placement of bilateral metallic stents has been considered difficult and complicated. Although the Y-stent with a central wide-open mesh facilitates bilateral stent placement, it has limitations. This study evaluated the feasibility and efficacy of the Niti-S large CP-868596 cell D-type biliary stent (LCD) with a uniform large cell for both uni- and bilateral drainage of malignant hilar biliary obstruction.\n\nFrom April

2008 to March 2009, a total of 12 consecutive patients with unresectable malignant hilar biliary obstruction of Bismuth type 2 or greater underwent placement of LCD. Before LCD placement,

all the patients underwent endoscopic unilateral biliary drainage using a plastic stent or a nasobiliary drainage tube. If jaundice improved after the procedure, the plastic stent or nasobiliary drainage tube was replaced with the unilateral LCD. If jaundice did not resolve or contralateral cholangitis occurred, bilateral LCD placement was performed.\n\nSeven patients had unilateral and five patients had bilateral LCD placement. Technical DAPT success was achieved for all 12 patients. An early complication occurred for one patient (8%), and stent occlusion occurred for six patients (50%) because of tumor ingrowth (n = 4) or sludge (n = 2). These patients were managed by insertion of plastic stents (n = 4) or percutaneous transhepatic biliary drainage (n = 2). The median stent patency period was 202 days.\n\nThe newly 123 designed endoscopic metallic stent may be feasible and effective for malignant hilar biliary obstruction, and endoscopic reintervention is relatively simple.”
“Objective: A major challenge in the management of patients with complex regional pain syndrome 1 is identifying those individuals who are at risk of developing severe problems. Data from large follow-up studies providing empirical evidence are largely lacking. The goal of this study was to obtain an expert-agreed priority list of parameters that are correlated with a poor prognosis.

The

binding constant (K) value as determined from fluores

The

binding constant (K) value as determined from fluorescence experiments of Selleckchem BMN 673 complexes 5 and 6 were calculated to be 4.09 x 10(4) and 2.51 x 10(4) M-1, respectively revealing that complex 5 has greater binding propensity for DNA. To gain further insight into the molecular recognition at the target site, interaction studies of 5 with 5′-GMP were carried out by employing H-1 and P-31 NMR spectroscopy. Complex 5 exhibited preferential selectively towards the minor groove of pBR322 DNA and efficient cleavage activity via hydrolytic pathway. Furthermore complexes 4-6 exhibited significant antimicrobial activity. (C) 2012 Elsevier B.V. All rights reserved.”
“About 30% of all 4 female ‘groin’ hernias are femoral hernias, although often only diagnosed during surgery. A Lichtenstein repair though, as preferred treatment modality according to guidelines, would not diagnose and treat check details femoral hernias. Totally extraperitoneal (TEP) hernia repair, however, offers the advantage of being an appropriate modality for the diagnosis

and subsequent treatment of both inguinal and femoral hernias. TEP therefore seems an appealing surgical technique for women with groin hernias.\n\nThis study included all female patients a parts per thousand yen18 years operated for a groin hernia between 2005 and 2009.\n\nA total BMS345541 of 183 groin hernias were repaired in 164 women. TEP was performed in 85% of women; the other 24 women underwent an open anterior (mesh) repair. Peroperatively,

femoral hernias were observed in 23% of patients with primary hernias and 35% of patients with recurrent hernias. There were 30 cases (18.3%) of an incorrect preoperative diagnosis. Peroperatively, femoral hernias were observed in 17.3% of women who were diagnosed with an inguinal hernia before surgery. In addition, inguinal hernias were found in 24.0% of women who were diagnosed with a femoral hernia preoperatively. After a follow-up of 25 months, moderate to severe (VAS 4-10) postoperative pain was reported by 8 of 125 patients (6.4%) after TEP and 5 of 23 patients (21.7%) after open hernia repair (P = 0.03). Five patients had a recurrent hernia, two following TEP (1.4%) and three following open anterior repair (12.5%, P = 0.02). Two of these three patients presented with a femoral recurrence after a previous repair of an inguinal hernia.\n\nFemoral hernias are common in women with groin hernias, but not always detected preoperatively; this argues for the use of a preperitoneal approach. TEP hernia repair combines the advantage of a peroperative diagnosis and subsequent appropriate treatment with the known good clinical outcomes.”
“The primary management of lymph nodes involved with metastatic melanoma is regional lymphadenectomy.

Methods: All

perforator-supercharged occipitocervicop

\n\nMethods: All

perforator-supercharged occipitocervicopectoral flaps that were used for face and neck reconstructions were analyzed retrospectively.\n\nResults: In all nine cases, the second 4 internal mammary artery perforator was attached at the end of the occipitocervicopectoral flap and supercharged with the contralateral recipient facial artery vessels. The average flap size was 22.6 x 6.2 cm, without BVD-523 any flap loss. It was possible to cover a large defect extending to bilateral sides with thin and pliable local skin tissue. All patients were satisfied with functional and aesthetic results achieved postoperatively after 6 months.\n\nConclusions: The internal MLN4924 in vivo mammary artery perforator-supercharged occipitocervicopectoral flap can be considered a type of bipedicle perforator flap and can provide reliable flap vascularity. By using a perforator supercharging technique, we can adjust and enlarge the flap length tailored to the defect. (Plast. Reconstr. Surg. 129: 879, 2012.)\n\nCLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.”
“Plants are unique in their ability to continuously produce new meristems and organ primordia.

In Arabidopsis, the transcription factor LEAFY (LFY) functions as a master regulator of a gene network that is important for floral meristem and organ specification. UNUSUAL FLORAL ORGANS (UFO) is a co-activator of LEAFY and is required for proper activation of APETALA3 in the floral meristem during the specification of stamens and petals. The ufo mutants display defects in other parts of the flower and the inflorescence, suggestive of additional roles. Here we show that the normal determinacy of the developing Arabidopsis leaves is affected by the expression of a gain-of-function UFO P505-15 concentration fusion protein with the VP16 transcriptional activator domain. In these lines, the rosette and cauline leaf

primordia exhibit reiterated serration, and upon flowering produce ectopic meristems that develop into flowers, bract leaves and inflorescences. These striking phenotypes reveal that developing leaves maintain the competency to initiate flower and inflorescence programs. Furthermore, the gain-of-function phenotypes are dependent on LFY and the SEPALLATA (SEP) MADS-box transcription factors, indicative of their functional interactions with UFO. The findings of this study also suggest that UFO promotes the establishment of the lateral meristems and primordia in the peripheral zone of the apical and floral meristems by enhancing the activity of LFY. These novel phenotypes along with the mutant phenotypes of UFO orthologs in other plant species suggest a broader function for UFO in plants.”
“Decision making (DM) in the context of others often entails complex cognition-emotion interaction.

However, youth with ADHD showed

However, youth with ADHD showed this website greater activation in the left dorsolateral prefrontal cortex (DLPFC) and left posterior cingulate cortex (PCC), greater functional

connectivity between the left DLPFC and left intraparietal sulcus, and reduced left DLPFC connectivity with left midcingulate cortex and PCC for the high load contrast compared to controls (p smaller than .01; k bigger than 100 voxels). Reanalysis using a more conservative statistical approach (p smaller than .001; k bigger than 100 voxels) yielded group differences in PCC activation and DLPFC-midcingulate connectivity. Conclusion: Youth with ADHD show 432 decreased efficiency of DLPFC for high-load visuospatial working memory and greater reliance on posterior spatial attention circuits to store and update spatial position than healthy control youth. Findings should be replicated in larger samples.”
“About 2000 tons of chrysotile is used annually to produce friction materials in Islamic find more Republic

of Iran. Approximately, 3000 workers are exposed to the asbestos fibers in the different processes of brake and clutch manufacturing. In the current study, asbestos fiber concentrations during brake and clutch manufacture were measured. This study also evaluated the fiber size and morphology distribution according to the Asbestos International Association (AIA) for standardization analytical method for asbestos.\n\nThe airborne asbestos fiber concentrations buy Crenigacestat and its chemical composition of 92 personal samples were analyzed by phase contrast microscopy (PCM)

and scanning electron microscope (SEM) equipped with an energy-dispersive X-ray analyzer (EDX).\n\nPersonal monitoring of fiber levels demonstrated counts that ranged from 0.31 to 1.3 PCM f/ml ( 15.5-51.5 SEM f/ml). Geometric means of the asbestos concentrations were 1.3 PCM f/ml (51.5 SEM f/ml) and 0.86 PCM f/ml (42.1 SEM f/ml) according to the brake weighting and mixing and clutch mixing process, respectively. The geometrical mean concentrations were 0.63 PCM f/ml (31 SEM f/ml), which is considerably higher than threshold limit value (TLV) of the American Conference of Governmental Industrial Hygienists (ACGIH) which is 0.1 f/ml. The SEM data demonstrate that the fibrous particles consisted, approximately, of chrysotile (50%), tremolite (30%), and actinolite (20%).\n\nBased on these findings, the 50% of airborne fibers inhaled by the workers were amphiboles asbestos with fibers equal and greater than 5 mu m in length and 0.2 mu m in diameter, and thus not included in the PCM-based fiber counts. Therefore, it might be expected that workers who worked in the brake and clutch manufacture will suffer from negative health effects of exposing to the amphibole asbestos fibers. (C) 2009 Elsevier Inc. All rights reserved.