Results: The FOMs comparing the analytical model to MANTIS fo

\n\nResults: The FOMs comparing the analytical model to MANTIS for these parameters were 0.1951 +/- 0.0011, 0.1915 +/- 0.0014, 0.2266 +/- 0.0021, and 0.2416 +/- 0.0074 for 0 degrees, 15 degrees, 30 degrees,

and 45 degrees, respectively. As a comparison, the same FOMs comparing MANTIS to 2D symmetric Gaussian fits to the zero-angle PRF were 0.6234 +/- 0.0020, 0.9058 +/- 0.0029, 1.491 +/- 0.012, and 2.757 +/- 0.039 for the same set of incidence angles. Therefore, the analytical model matches MANTIS results much better than a 2D symmetric Gaussian function. A comparison was also made against experimental data for a 170 mu m thick CsI screen and an x-ray energy of 25.6 keV. The corresponding FOMs were 0.3457 +/- 0.0036, 0.3281 +/- 0.0057, 0.3422 +/- 0.0023, and 0.3677 +/- 0.0041 for 0 degrees, 15 degrees, selleck chemicals 30 degrees, and 45 degrees, respectively. In a previous study, FOMs comparing the same experimental data to MANTIS PRFs were found to be 0.2944

+/- 0.0027, 0.2387 +/- 0.0039, 0.2816 +/- 0.0025, and 0.2665 +/- 0.0032 for the VX-770 Transmembrane Transporters inhibitor same set of incidence angles.\n\nConclusions: The two sets of derived FOMs, comparing MANTIS-generated PRFs and experimental data to the analytical model, demonstrate that the analytical model is able to reproduce experimental data with a FOM of less than two times that comparing MANTIS and experimental data. This performance is achieved in less than one millionth the computation time required to generate a comparable PRF with MANTIS. Such

small computation times will allow for the c-Met inhibitor inclusion of detailed detector physics in rigorous optimization and reconstruction algorithms for 3D x-ray breast imaging systems. [DOI: 10.1118/1.3397462]“
“Background: PHACE syndrome describes a spectrum of anomalies associated with large facial infantile hemangiomas and characterized by posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. With improved recognition and imaging practices of infants with PHACE syndrome, additional associations have been identified. To our knowledge, the potential association of ipsilateral hearing loss and PHACE syndrome has not been previously emphasized.\n\nObservations: We describe 6 patients, 4 with definite and 2 with probable PHACE syndrome, according to the new diagnostic criteria, and associated auditory deficiencies. One patient had isolated conductive hearing loss; 2 patients had isolated sensorineural hearing loss; 1 patient had mixed hearing loss (both conductive and sensorineural components); and 1 patient had hearing loss that was inconclusive at the time. Also, 1 patient had conductive loss and auditory neuropathy and auditory dys-synchrony.

The initial focus is on the various sources of bias and variance

The initial focus is on the various sources of bias and variance in the measurement of microvascular parameters and diffusion parameters as such parameters are being used relatively commonly as secondary or exploratory end points in current phase 1/2 Momelotinib chemical structure clinical trails of conventional and targeted therapies. Several ongoing initiatives that seek to identify the magnitude of some of the sources of measurement variations are then discussed. Finally, resources being made available through the National Cancer Institute Reference Image Database to Evaluate Response (RIDER) project that might be of use in investigations of quantitative

MRI biomarker change analysis are described. These resources include 1) data from phantom-based assessment of system response, Entinostat mouse including short-term (1 hour) and moderate-term (1 week) contrast response and relaxation time measurement, 2) data obtained from repeated dynamic contrast agent-enhanced MRI studies in intracranial tumors,

and 3) data obtained from repeated diffusion MRI studies in both breast and brain. A concluding section briefly discusses issues that must be addressed to allow the transition of MR-based imaging biomarker measures from their current role as secondary/exploratory end points in clinical trials to primary/surrogate markers of response and, ultimately, in clinical application.”
“Analysis and modeling of impedance spectroscopy data of ferroelectric BaTi2O5 single crystal has been carried out at temperatures both below and above the ferroelectric Curie temperature, T-C. The most appropriate equivalent circuit is found to consist of a parallel combination of a resistor (R), capacitor (C), and constant phase element

(CPE). Below TC, the resistance R is too large to measure and the circuit simplifies to C-CPE. Above T-C, R shows Arrhenius behavior with low values of conductivity, https://www.selleckchem.com/products/nu7441.html eg similar to 4 X 10(-7) S cm(-1) at 800 K and high activation energy, 1.13(2) eV, and represents a thermally activated dc hopping process associated with leakage transport of either electrons or holes through the crystal lattice. C is frequency-independent, passes through a maximum at the ferroelectric-paraelectric transition temperature, T-C similar to 475 degrees C, represents the limiting high frequency capacitance of the crystal and is attributed to the response of the individual dipoles that are responsible for the ferroelectricity. The A parameter of the CPE also passes through a maximum at T-C, is not thermally activated in the same manner as R but shows similar temperature dependence to that of C.


“Germline transformation with transposon vectors is an imp


“Germline transformation with transposon vectors is an important tool for insect genetics, but progress in developing transformation

protocols for butterflies has been limited by high post-injection ova mortality. Here we present an improved glass injection needle design for injecting butterfly ova that increases survival in three Nymphalid butterfly species. Using the needles to genetically transform the common buckeye butterfly Junonia coenia, the hatch rate for injected Junonia ova was 21.7%, the transformation learn more rate was 3%, and the overall experimental efficiency was 0.327%, a substantial improvement over previous results in other butterfly species. Improved needle design and a higher efficiency of transformation should permit the deployment of transposon-based genetic tools in a broad range of less fecund lepidopteran species.”
“A sensitive, reliable this website and accurate

reversed-phased liquid chromatography with tandem mass spectrometry (LC-MS/MS) in negative ion mode was developed and validated for the quantification of tenuifolin in rat plasma and tissue. A single step protein precipitation by methanol was used to prepare plasma and tissue homogenate samples. Tenuifolin and polydatin (internal standard, IS) were separated by HPLC using a C18 column and an isocratic mobile phase consisted of acetonitrile and water containing 0.05% formic acid (42:58, v/v) running at a flow rate of 0.2 ml/min for 6 min. Detection

and quantification were performed using a mass spectrometer by the multiple reaction BLZ945 molecular weight monitoring (MRM) in negative electrospray ionization mode. The transition monitored were m/z [M-H](-) 679.4 – bigger than 455.4 for tenuifolin and m/z [M-H](-) 389.0 – bigger than 227.2 for IS. respectively. Calibration curves were recovered over a concentration range of 0.5-1000 ng/ml for plasma, heart, liver, lung and kidney, 0.5-200 ng/ml for spleen, and 0.5-50 ng/ml for brain, respectively. The lower limit of quantification was 0.5 ng/ml for plasma and tissue homogenates. The inter-day precision (R.S.D.) was less than 12.9% and intra-day precision R.S.D. was less than 13.4%, while the inter-day accuracy (RE.) was ranged from -7.20 to 6.87% and intra-day accuracy (R.E.) was ranged from -6.20 to 8.04% in plasma and tissue homogenates. This method was successfully applied to the pharmacokinetic and tissue distribution study of pure tenuifolin in rat. The pharmacokinetic study indicated that poor absorption into systemic circulation was observed after rat was administered orally tenuifolin, and the absolute bioavailability was low (0.83 +/- 0.28%). The results of tissue distribution showed the higher tenuifolin concentrations were found in liver, kidney and heart, and the small amount of drug was distributed quickly into the brain tissue at 5 min after the intravenous injection of tenuifolin.

Here we shift focus to the neglected southern and interior AF by

Here we shift focus to the neglected southern and interior AF by addressing the phylogeography of the mouse Akodon montensis as inferred through analysis of cytochrome-b gene sequences of 86 specimens collected at 36 localities

in Argentina, Brazil, and Paraguay. Three main clades were recovered with average genetic divergence of 2.5%; a northern clade, differentiated in the Bahia refuge, a southern clade for which we propose the Rio Grande do Sul refugium- and a central clade (widely extending from coastal Brazil to Argentina and Paraguay). Within the latter, genetic diversity and historical demographic estimations support differentiation in the Sao Paulo refugium and their later population expansion toward interior AF. Additionally, no riverine barrier effect was found associated with the main river in the interior AF, the Parana River.

this website Taken as a whole, the phylogeographic pattern of A. montensis and its recent population history are mainly concordant with the CM model.”
“The variability in the characteristics of fresh meat and thighs in relationship with genetic type PXD101 in vitro was studied on 22 lots of heavy pigs, comprising 615 female and castrated males, randomly chosen during slaughtering in groups of 20 to 30 animals per lot. Four different genetic types reared for the production of the San Daniele dry-cured ham PDO were considered: two traditionals (Large White or Duroc x (Landrace x Large White) and two industrial hybrids (GOLAND and DANBRED). Fresh meat samples from longissimus dorsi muscle were collected to perform chemical and physical analysis. The right trimmed thighs were used to evaluate some morphological parameters along with weight losses during seasoning. The genetic

type confirmed its important influence on pig carcass, meat and ham quality. The two industrial types, DANBRED in particular, tended to present a lower back fat values and a leaner carcass than the two Italian genetic types. Within the most important characteristics for the production Autophagy Compound Library ic50 of dry cured hams (subcutaneous fat thickness and seasoning losses) the highest differences were found among the industrials genetic types, which cannot be simply considered as an undifferentiated homogenous group.”
“Ischemic heart disease and myocardial infarction continue to be leading causes of cardiovascular morbidity and mortality. Activation of opioid, adenosine, bradykinin, adrenergic and other G-protein coupled receptors has been found to be cardioprotective. kappa- and/or delta-opioid receptor activation is involved in direct myocardial protection, while the role of mu-opioid receptors seems less clear. In addition, differential affinities to the three opioid-receptor subtypes by various agonists and cross-talk among different G-protein coupled receptors render conclusions regarding opioid-mediated cardioprotection challenging.

38), CE indication (P = 0 24), CE lesion

38), CE indication (P = 0.24), CE lesion VX-809 manufacturer location (P = 0.29), days between CE and SE (P = 0.30), and depth of insertion (P = 0.81). Type of CE findings (particularly AVMs) significantly affected SE reproducibility (P = 0.015). SE procedure time was inversely related to SE reproducibility (odds ratio = 0.94, 95% confidence interval = 0.88-0.99, P = 0.02).\n\nLimitations: Small sample size and potential for false-positive CE study.\n\nConclusions: SE seems to be moderately effective (57.1%) in terms of its ability to locate pathology within the small intestine. The type of small bowel pathology targeted by SE may affect its clinical utility.

AVMs observed on CE can be seen at the time of SE in the majority of cases (60%).”
“This study evaluated the antiplatelet effects of clopidogrel (CPG) in patients sustaining acute ischemic stroke who were already receiving chronic outpatient aspirin therapy (81-325 mg/day). Platelet function was measured using 3 different “point-of-care” platelet function analyzers: the Thrombelastograph hemostasis system, the Accumetrics VerifyNow system, and the Chronolog 570VS impedance aggregometer.

Platelet function was assessed before administration of a 300-mg CPG loading dose and again at 26 hours and 64 hours after this loading dose along with a 75-mg daily maintenance dose. All 3 instruments detected marked inhibition of platelet function at 26 hours and 64 hours after CPG administration. There were significant variations among the 3 instruments in monitoring antiplatelet responses to aspirin and CPG; however, these variations were eliminated Selleckchem MAPK inhibitor when the platelet

function results were corrected for baseline platelet variability. The percentage of patients who were poor responders to CPG after switching from aspirin depended on the measurement instrument used, but was higher at 26 hours after CPG administration than at 64 hours after CPG administration. Our findings indicate that poor response to antiplatelet agents in general, and to CPG in particular, is a function of the measuring instrument. The correction for baseline platelet variability results in similar levels of platelet inhibition measured by the 3 platelet function analyzers. Future studies are warranted to examine the association between ex vivo CPG-induced Cl-amidine platelet inhibition and clinical outcomes in patients with ischemic stroke.”
“Background:\n\nSince 2009 UK GPs have been incentivised to use depression severity scores to monitor patients’ response to treatment after 5-12 weeks of treatment.\n\nAim:\n\nTo examine the association between the severity scores obtained and follow-up questionnaires to monitor depression and subsequent changes made to the treatment of it.\n\nDesign and setting:\n\nA retrospective cohort study utilising routine primary care records was conducted between April 2009 and March 2011 in 13 general practices recruited from within Hampshire, Wiltshire, and Southampton City primary care trusts.

Recognizing that the theranostics of the future could offer a fre

Recognizing that the theranostics of the future could offer a fresh approach to the treatment of degenerative diseases including cancer, we aim LY2835219 to start moving out of the chemical domain and into the biological one. Some MSNPs are already being tested in biological systems.”
“von Willebrand’s

disease (vWD) is the commonest inherited bleeding disorder. Although in literature there are some cases reported of epidural analgesia for labor pain in pregnancies with Von Willebrand’s disease, the technique is not free from risk of neurolocal complications. Authors reported a case of spontaneous labor in a pregnant woman with type II vWD, delivered under local analgesia administered through a continuous intravenous infusion of remifentanil integrated by boli. A 34-year-old woman at the 39(th) week of her second pregnancy was admitted for an active labor of a single fetus in cephalic presentation. The patient had been diagnosed with type H vWD by a hematologist during her first pregnancy. The patient coagulation panel was as follows: a reduction of VIII(th) factor concentration (21%); a normal value of vWD functional assay; an increase of vWf:Ag (antigen)

and a reduction of XI(th) factor. During labor she was put on remifentanil in PCA (patient controlled analgesia), administered with slow boli followed by continuous infusions at increasing doses. The woman delivered a female fetus weighing 3,550 g, in vertex presentation, in left anterior selleck occipital position, with an A.P.G.A.R. of 8 at the first minute and 9 at the fifth minute. The total duration of labor was 3 hours and 10 minutes. The patient was satisfied with analgesia in labor. The bleeding during and after delivery was regular. In the authors’ opinion, it is important to know that an alternative to epidural analgesia can be used in order to avoid the risk of neurological complications in labor pain for patients with type II Von Willebrand’s disease.”
“Fenofibrate, a fibric acid derivative, is frequently used to treat diabetic dyslipidemia and hypertriglyceridemia alone or in combination with statins. Rhabdomyolysis is a syndrome that results from striated muscle necrosis and release of its contents into the

systemic circulation and extracellular fluid. Fenofibrate-induced rhabdomyolysis is a rare clinical condition if there CH5424802 is not a predisposing factor such as diabetes mellitus, hypothyroidism, and renal insufficiency. In this study, we present a case of a patient who developed rhabdomyolysis after micronized fenofibrate use without known predisposing factor.”
“Background Catheter-related bloodstream infection remains an important health problem for hospitalized children. Although placement of a central venous catheter is a life-saving intervention for critically ill children, these same central catheters are a potential source of infection.\n\nObjectives Few studies that directly address care of central venous catheters for children in intensive care units have been reported.

Here we show proof-of-concept of a two-step synthesis that can be

Here we show proof-of-concept of a two-step synthesis that can be used to create similar constructs targeted to glioblastoma cells. Specifically, a well-defined aldehyde side chain polymer was synthesized and oxime chemistry was employed to conjugate ligands specific for the alpha(6)beta(1)-integrin. These constructs were then tested in competitive binding, fluorescence binding, and toxicity assays, through which we

demonstrate that constructs are multivalent, preferentially target glioblastoma cells, and are nontoxic. Rapid, potentially low-cost synthesis of targeting constructs will enable their use in the clinic and for personalized medicine.”
“Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides. Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6. Vorinostat molecular weight We have determined the crystal structures of TLR2-TLR6-diacylated lipopeptide,

TLR2-lipoteichoic acid, and TLR2-PE-DTPA complexes. PE-DTPA, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-diethy-lenetriaminepentaacetic acid, is www.selleckchem.com/products/ipi-145-ink1197.html a synthetic phospholipid derivative. Two major factors contribute to the ligand specificity of TLR2-TLR1 or TLR2-TLR6 heterodimers. First, the lipid channel of TLR6 is blocked by two phenylalanines. Simultaneous mutation of these phenylalanines made TLR2-TLR6 fully responsive not only to diacylated but also to triacylated lipopeptides. Second, the hydrophobic dimerization interface of TLR2-TLR6 is increased by 80%, which compensates for the lack of amide lipid interaction between the lipopeptide and TLR2-TLR6. The structures of the TLR2-lipoteichoic acid and the TLR2-PE-DTPA complexes demonstrate that a precise interaction pattern of the head group is essential for a robust immune response by TLR2 heterodimers.”
“The present study investigated whether

differences between adults and children in mechanical power during single-joint knee extension tasks and the complex multijoint task of jumping could be explained by differences in the quadriceps femoris muscle volume. Peak power was calculated during squat jumps, from the integral of the vertical force measured by a force plate, BKM120 cost and during concentric knee extensions at 30, 90, 120, 180 and 240 deg.s(-1), and muscle volume was measured from magnetic resonance images for 10 men, 10 women, 10 prepubertal boys and 10 prepubertal girls. Peak power during jumping and isokinetic knee extension was significantly higher in men than in women, and in both adult groups compared with children (P < 0.01), although there were no differences between boys and girls. When power was normalized to muscle volume, the intergroup differences ceased to exist for both tasks. Peak power correlated significantly with quadriceps volume (P < 0.01), with r(2) values of 0.8, 0.86, 0.81, 0.78 and 0.

Both evolutionarily conserved and evolutionarily new C2 domains o

Both evolutionarily conserved and evolutionarily new C2 domains of human Nedd4L, a cryptic splice variant resulting in a disrupted isoform product formed this website by a frame-shift mutation, were reported previously. We focused on one of the isoforms, isoform I, generated by SNP (rs4149601), and studied its expression and interactions with other isoforms by molecular biological, immunohistochemical, and electrophysiological methods. We found that isoform I may interact with other human isoforms in a dominant-negative fashion. Such interactions might abnormally increase sodium reabsorption. Taken together, our analyses suggest that the

human Nedd4L gene, especially the evolutionarily new isoform I, is a candidate gene for hypertension.”
“Hypobaric hypoxia leads to cognitive dysfunctions due to increase in intracellular calcium through ion channels. The purpose of this study was to examine the temporal contribution of L-type calcium channels and N-methyl-D-aspartate receptors (NMDARs) in mediating neuronal death in male Sprague Dawley rats exposed to hypobaric hypoxia simulating an altitude of 25,000 ft for different durations. Decreasing exogenous calcium loads by blocking voltage-gated calcium

influx with isradipine Captisol in vivo (2.5 mg kg(-1)), and its efficacy in providing neuroprotection and preventing memory impairment following hypoxic exposure was also investigated. Effect of isradipine on calcium-dependent enzymes mediating oxidative stress Saracatinib and apoptotic cell death was also studied. Blocking of L-type calcium

channels with isradipine reduced hypoxia-induced activation of calcium dependent xanthine oxidases, monoamine oxidases, cytosolic phospholipase A(2) and cycloxygenases (COX-2) along with concomitant decrease in free radical generation and cytochrome c release. Increased expression of calpain and caspase 3 was also observed following exposure to hypobaric hypoxia along with augmented neurodegeneration and memory impairment which was adequately prevented by isradipine administration. Administration of isradipine during hypoxic exposure protected the hippocampal neurons following 3 and 7 days of exposure to hypobaric hypoxia along with improvement in spatial memory. (C) 2009 Elsevier Inc. All rights reserved.”
“Mycoplasma contamination is a frequent problem in chlamydial cell culture. After obtaining contradictory contamination results, we compared three commercial PCR kits for mycoplasma detection. One kit signaled contamination in mycoplasma-free Chlamydia pneumoniae cultures. Sequencing of cloned PCR products revealed primer homology with the chlamydial genome as the basis of this false-positive result.

These data suggest that basal PIKA activity enhances SR Ca2+ rele

These data suggest that basal PIKA activity enhances SR Ca2+ release in the absence of E-adrenergic stimulation. This may depress contractile function in models such as

aging, where the cAMP/PIKA pathway is altered due to low basal cAMP levels. (C) 2012 Elsevier B.V. All rights reserved.”
“Background: The number of adults BGJ398 with congenital heart disease (CHD) is increasing rapidly, but care programs have not been fully established in Japan.\n\nMethods and Results: Questionnaires regarding current status and resources of outpatient and in-hospital services, and management of pregnancy in patients with adult CHD (ACHD) were sent to 1,033 training hospitals for board-certified cardiologists. Useful replies were obtained from 458 hospitals (44%). In 417 hospitals (91%), at least I patient was followed in the outpatient clinic; however, only 14 hospitals (3%) had specialized outpatient clinics; 354 hospitals (77%) had in-hospital patients, but only 6 hospitals (2%) admitted >50 patients per year. Surgery for ACHD was performed in 232 hospitals (51%), but in 135 of these (58%), the number of operations was <5

per year. Pregnant women with CHD were managed in 157 hospitals (34%), although only 3 hospitals (2%) managed >10 cases per year.\n\nConclusions: In most hospitals in Japan, a limited PND-1186 inhibitor number of ACHD patients have been followed up and specialized multi-disciplinary facilities for ACHD need Small molecule library nmr to be established. (Circ J 2009; 73: 1147-1150)”
“Pads of beetles are covered with long, deformable setae, each ending in a micrometric terminal plate coated with secretory fluid. It was recently shown that the layer of the pad secretion covering the terminal plates is responsible for the generation of strong attractive forces. However, less is known about the fluid itself because it is produced in an extremely small quantity. We present here the first experimental investigation of the rheological properties of the pad secretion in the Colorado potato beetle Leptinotarsa decemlineata (Coleoptera, Chrysomelidae). Because the secretion is produced in an extremely small amount

at the level of the terminal plate, we first developed a procedure based on capillary effects to collect the secretion for rheological experiments. In order to study the collected fluid (less than 1 nl) through passive microrheology, we managed to incorporate micrometric probes (melamine beads) that were initially in the form of a dry powder. Finally, the bead thermal motions were observed optically and recorded to determine the mechanical properties of the surrounding medium. We achieved this quantitative measurement with the collected volume, which is much smaller than the usual 1 mu l sample volume required for this technique. Surprisingly, the beetle secretion was found to behave as a purely viscous liquid, of high viscosity (about 100 times that of water).

Methods: Sixty CHB patients with positive HBeAg were equally rand

Methods: Sixty CHB patients with positive HBeAg were equally randomized by digital table into two groups: the observation group and the control group. Patients in the control group were treated with lamivudine only, while patients in the observation group were treated with lamivudine combined with SPNS fomula, for 12 weeks. The phenotype ACY-1215 manufacturer and function of dendritic cell, as well as its secretion factor interleukin 12 (IL-12) in all patients were determined after termination of therapy and the impacts on alanine transaminase (ALT) and HBV-DNA were observed. Results: The phenotypes of dendritic cells such as CD1a,

CD80, CD86, human leukocyte antigen (HLA-DR) and intercellular 4EGI-1 nmr adhesion molecule-1, as well as the levels of stimulation index (SI) and IL-12 were higher in the observation group than those in the control group (P<0.05 or P<0.01). Meanwhile, significant difference between the two groups was also shown in the normalizing rates of ALT and HBV-DNA (P<0.05). Conclusion: TCM therapy for SPNS can significantly improve

the function of dendritic cells in patients with CHB treated by lamivudine and enhance the early stage response of patients to the treatment.”
“When fractionation of meat lipids is not required. procedures such as saponification can be used to extract total fatty acids, reducing reliance on toxic organic compounds. However, saponification of muscle fatty acids is laborious, and requires extended heating times, and a second methylation step to convert the extracted fatty acids to fatty acid methyl esters prior to gas chromatography. Therefore the development of a more rapid direct methylation procedure would be of merit. The use of freeze-dried material

for analysis is common and allows for greater homogenisation of the sample. The present study investigated the potential of using freeze-dried muscle samples and a direct bimethylation to analyse total fatty acids of meat (beef, chicken and lamb) in comparison with a saponification procedure followed by bimethylation. Both methods selleck inhibitor compared favourably for all major fatty acids measured. There was a minor difference in relation to the C18:1 trans 10 isomer with a greater (P<0.05) recovery with saponification. However, numerically the difference was small and likely as a result of approaching the limits of isomer identification by single column gas chromatography. Differences ( P<0.001) between species were found for all fatty acids measured with no interaction effects. The described technique offers a simplified, quick and reliable alternative to saponification to analyse total fatty acids from muscle samples. (C) 2012 Elsevier Ltd. All rights reserved.