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A new technology of austenite grain refinement, fine austenite enhanced ferrite transformation, is proposed for heavy‐duty hot‐rolled H‐beam steels in this work. Titanium microalloying is very important and necessary for the new technology. The effect of titanium on the prior austenite grain size of steels during simulated rough rolling was investigated. The results show that the prior austenite grain sizes of specimens with titanium and niobium elements are much finer than those of specimens with niobium but without titanium deformed at the same parameters. For the alloying composition of studied steels, titanium nitride particle maybe precipitated in specimens with titanium at above 1,200 °C, however, niobium carbide particles can't form in specimens without titanium at above 1,150 °C. The thermodynamically stable titanium nitride particles can impede the grain growth at high temperature for example furnace heating before rough rolling and bring the epitaxial growth of niobium carbide on pre‐existing themselves which induces a large number of titanium nitride‐niobium carbide composite precipitates. These fine precipitates can pin austenite grain boundaries effectively and ensure austenite grain refinement. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A is widely used in the manufacture of polycarbonate plastics and has caused increasing concern over its potential adverse impacts on spermatogenesis. However, the effect of bisphenol A on spermiogenesis is yet to be explored. Objectives: To evaluate whether bisphenol A has adverse effects on DNA integrity and protamination of spermatogenic cell. Materials and methods: Newborn male mice were subcutaneously injected with bisphenol A (0.1, 5 mg/kg body weight, n = 15) or coin oil (control group, n = 20) daily from post‐natal day 1 until 35. At post‐natal day 70, epididymis caudal spermatozoa and testes were collected. Sperm count, sperm motility, and sperm morphology were analyzed. The sperm chromatin structure assay was performed to examine the sperm DNA fragmentation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method was used to assess apoptosis of spermatogenic cells. The ultrastructural features of testicular sections were examined under a transmission electron microscope. Western blot and RT‐PCR were used to detect the expression levels of transition protein (Tnp) 1 and Tnp2, protamine (Prm) 1 and Prm2 protein, and mRNA in mice testes. Results: Bisphenol A significantly reduced sperm counts, impaired sperm motility, and increased the percentage of malformed spermatozoa. Poor sperm chromatin integrity and increased TUNEL‐positive spermatogenic cells were also observed in mice exposed to bisphenol A. Ultrastructural analysis of testes showed that bisphenol A exposure caused incomplete chromatin condensation, retention of residual cytoplasm, and abnormal acrosome formation. In addition, the relative expression levels of Tnp2 and Prm2 in mice testes decreased significantly in bisphenol A groups. Discussion and conclusion: Our findings identified that neonatal bisphenol A exposure may negatively contribute to the sperm quality in adult mice. Mechanistically, we showed that bisphenol A reduced sperm chromatin integrity along with increased DNA damage, which may be due to poor protamination of spermatozoa. [ABSTRACT FROM AUTHOR]

Summary: Embryonic survival rate, an important factor in the fecundity of sows, is affected by endometrium‐secreting histotroph. A higher concentration of calcium ion has been observed in the uterus of highly prolific Erhualian sows (EH) compared with those of less prolific (EL) sows. This suggests that EH sows have better establishment and maintenance of pregnancies, thus increasing embryonic survival rate during the peri‐implantation period. To understand the mechanisms of how the endometrium‐secreting histotroph affects embryonic survival rate during the Erhualian peri‐implantation period, the expression patterns of endometrial mRNA in the EH and EL sows on day 12 of gestation were analyzed using RNA sequencing technology. A total of 164 differentially expressed genes (DEGs) were identified (Padj < 0.05, |log2(FC)| ≥ 1), including 46 upregulated and 118 downregulated genes in EH compared to EL. Gene Ontology enrichment indicated that a subset of DEGs was involved in calcium ion binding and cell adhesion. Solute carrier family 8 member A3 and solute carrier family 24 member 4, identified as upregulated genes (Padj < 0.05) in EH, were considered key candidate genes expressed in the endometrium affecting embryonic survival rate during the peri‐implantation period. The results improve understanding of the genetic mechanism underlying the variation in litter size of Erhualian pigs during the peri‐implantation period. [ABSTRACT FROM AUTHOR]

SUMMARY: Background: Cross‐match‐compatible platelets can improve corrected count increments (CCIs) in alloimmunised patients with transfusion refractoriness. However, only a few studies mentioned that the specificities of platelet‐reactive alloantibodies can predict high reactivity in cross‐match assays among these patients. Methods: A total of 204 medical records of patients who were refractory to random single‐donor apheresis platelets between January 2014 and December 2014 were enrolled. Platelet‐reactive antibodies in patients' serum were screened by an enzyme‐linked immunosorbent assay (ELISA).The platelet cross‐match assays were performed by a solid‐phase adherence assay. The specificities of human leukocyte antigen (HLA) class I and human platelet antigens (HPAs) alloantibodies were determined by Luminex Single Antigen and Monoclonal Antibody‐specific Immobilization of Platelet Antigens (MAIPA) assays, respectively. Results: Anti‐HLA and anti‐HPA alloantibodies were found in 114 of 204 (55.88%) patients, including 110 (96.49%) with anti‐HLA alloantibodies only, 2 (1.75%) with anti‐HPA alloantibodies (anti‐GPIIb/IIIa) only and 2 (1.75%) with both anti‐HLA and anti‐HPA alloantibodies (anti‐HPA‐3a and anti‐HPA‐5b). The most common HLA class I alloantibody phenotypes in cross‐match‐incompatible patients were HLA‐A23 (59.38%), ‐A24 (50.00%), ‐A02 (43.75%), ‐B27 (65.63%), ‐B40 (50.00%), ‐B18 (46.88%) and ‐B07 (43.75%). A total of 480 cross‐matched platelet units were administered in 82 of 114 alloimmunised patients with a mean CCI of 7800 ± 5200, a significant improvement over random platelet units (P < 0.001). Conclusions: No development of additional platelet alloantibodies was observed during this platelet transfusion regiment. This study showed that transfusion of cross‐match‐compatible platelet units offers effective and safe management of platelet transfusion refractoriness (PTR). The finding of alloantibodies among cross‐match‐incompatible cases can be used as predictors for platelet donor selection. [ABSTRACT FROM AUTHOR]

Comparative pharmacokinetic profiles of diaveridine following single intravenous and oral dose of 10 mg/kg body weight in healthy pigs and chickens were investigated, respectively. Concentrations of diaveridine in plasma samples were determined using a validated high-performance liquid chromatography-ultraviolet ( HPLC- UV) method. The concentration-time data were subjected to noncompartmental kinetic analysis by WinNonlin program. The corresponding pharmacokinetic parameters in pigs or chickens after single intravenous administration were as follows, respectively: t1/2 β (elimination half-life) 0.74 ± 0.28 and 3.44 ± 1.07 h; V d (apparent volume of distribution) 2.70 ± 0.99 and 3.86 ± 0.92 L/kg; ClB (body clearance) 2.59 ± 0.62 and 0.80 ± 0.14 L/h/kg; and AUC0-∞ (area under the blood concentration vs. time curve) 4.11 ± 1.13 and 12.87 ± 2.60 μg∙h/mL. The corresponding pharmacokinetic parameters in pigs or chickens after oral administration were as follows, respectively: t1/2 β 1.78 ± 0.41 and 2.91 ± 0.57 h; Cmax (maximum concentration) 0.43 ± 0.24 and 1.45 ± 0.57 μg/ mL; Tmax (time to reach Cmax) 1.04 ± 0.67 and 3.25 ± 0.71 h; and AUC0-∞1.33 ± 0.55 and 9.28 ± 2.69 μg∙h/ mL. The oral bioavailability (F) of diaveridine in pigs or chickens was determined to be 34.6% and 72.2%, respectively. There were significant differences between the pharmacokinetics profiles in these two species. [ABSTRACT FROM AUTHOR]

Climate anomalies have resulted in changing forest productivity, increasing tree mortality in Central and Southern Europe. This has resulted in more severe and frequent ecological disturbances to forest stands. This study analysed the size-dependence of growth response to drought years based on 384 tree individuals of Norway spruce [ Picea abies (L.) Karst.] and European beech [ Fagus sylvatica ([L.)] in Bavaria, Germany., Samples were collected in both monospecific and mixed-species stands. To quantify the growth response to drought stress, indices for basal area increment, resistance, recovery and resilience were calculated from tree ring measurements of increment cores. Linear mixed models were developed to estimate the influence of drought periods., The results show that ageing-related growth decline is significant in drought years. Drought resilience and resistance decrease significantly with growth size among Norway spruce individuals. Evidence is also provided for robustness in the resilience capacity of European beech during drought stress. Spruce benefits from species mixing with deciduous beech, with over-yielding spruce in pure stands., The importance of the influence of size-dependence within tree growth studies during disturbances is highlighted and should be considered in future studies of disturbances, including drought. [ABSTRACT FROM AUTHOR]

The association between polymorphism of eNOS and male infertility in several studies was controversial. To explore a more precise estimation of the association, a meta-analysis of eight case-control studies, including 1,968 cases and 1,539 controls, were selected. The meta-analysis was conducted by calculating the pooled odds ratio (OR) with a 95% confidence interval (95% CI). Overall, the association between T786C and risk of male infertility was obvious (TC vs. TT: OR, 1.20; 95% CI, 1.01-1.42; CC vs. TT: OR, 3.37; 95% CI, 1.65-6.87; TC/CC vs. TT: OR, 1.47; 95% CI, 1.25-1.73; CC vs. TT/TC: OR, 3.18; 95% CI, 1.54-6.56; TC vs. TT: OR, 1.65; 95% CI, 1.27-2.03). However, no overall association was observed between the other two polymorphisms of eNOS ( G894T and 4a4b) and male infertility. Stratified analysis showed that significantly strong association between T786C polymorphism and semen quality was present in all three types of male infertility (azoospermia, oligozoospermia and asthenozoospermia). In the subgroup analysis based on ethnicity, both T786C and 4a4b could influence the risk of male infertility in Asian and Caucasian. Further studies of polymorphisms of eNOS with their biological functions are needed to understand the role in the development of male infertility. [ABSTRACT FROM AUTHOR]

Metformin, a synthetic dimethyl biguanide, has been in clinical use for over 55 years, and today is considered the first-choice drug for the treatment of type 2 diabetes used by an estimated 125 million people worldwide. Metformin is orally effective, not metabolized, excreted unchanged by the kidney, relatively free of side effects and well tolerated by the majority of patients. Of importance is that the United Kingdom Prospective Diabetes Study 20-year study of type 2 diabetics, completed in 1998, compared patients treated with insulin, sulfonylureas and metformin and concluded that metformin provided vascular protective actions. Cardiovascular disease is the primary basis for the high morbidity and mortality that is associated with diabetes and that metformin proved to be protective resulted in a dramatic increase in its use. The vascular protective actions of metformin are thought to be secondary to the antihyperglycaemic effects of metformin that are mediated via activation of AMP kinase and subsequent inhibition of hepatic gluconeogenesis, fatty acid oxidation as well as an insulin sensitizing action in striated muscle and adipose tissue. As reflected by a number of clinical studies, patients treated with metformin also have improvement in endothelial function as measured by the use of plethysmography and measurement of flow-mediated vasodilatation. These data as well as data from animal studies are supportive that metformin has a direct protective action on the vascular endothelium. In this review article, we discuss the pharmacology of metformin and critique the literature as to its cellular sites and mechanism(s) of action. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the oxidative status in ketotic cows. We observed changes in the oxidative status and correlations between the oxidative and metabolic status in non-ketotic ( n = 10), subclinical ketotic ( n = 10) and ketotic cows ( n = 10). Plasma samples were analysed by standard biochemical techniques and ELISA to determine traditional metabolic parameters: triglyceride ( TG), phosphonium (P), calcium (Ca), aspartate aminotransferase ( AST), alanine aminotransferase ( ALT), alkaline phosphatase ( ALP), total protein ( TP), albumin ( ALB), immune globulin (Ig), total cholesterol ( TC), high-density lipoprotein ( HDL), very low-density lipoprotein ( VLDL) and lactate dehydrogenase ( LDH); energy metabolism indices: glucose, β-hydroxybutyrate ( BHBA) and non-esterified fatty acids ( NEFA); and indices of oxidative status: malondialdehyde ( MDA), hydrogen peroxide (H2O2), vitamin C, vitamin E, superoxide dismutase ( SOD), glutathione peroxidase ( GSH-Px), catalase ( CAT), xanthine oxidase ( XOD) and total antioxidant capacity ( TAOC). The results of this study showed that plasma glucose levels were lower in ketotic and subclinical ketotic cows than in non-ketotic cows; however, the plasma NEFA and BHBA concentrations were higher. In addition, significant decreases in TC, HDL and VLDL and significant increases in AST, ALT and LDH were observed in the plasma of the ketotic cows. The ketotic cows showed decreased plasma SOD, CAT, vitamin C and vitamin E, inhibited hydroxyl radical capacity and increased plasma H2O2 and MDA. There were positive correlations between the plasma NEFA and ALT, AST, LDH and MDA and negative correlations between the plasma NEFA and TC, HDL, VLDL, SOD, vitamin C, vitamin E, 1542280 uric acid and inhibited hydroxyl radical capacity. In addition, there were positive correlations between BHBA concentrations and ALT, AST and LDH and negative correlations between plasma BHBA concentrations and TC, HDL, VLDL, vitamin E and inhibited hydroxyl radical capacity. Overall, ketotic dairy cows experience oxidative stress, which is presumably associated with hyperketonemia and higher NEFA. [ABSTRACT FROM AUTHOR]

SUMMARY Background Several studies had demonstrated that leucocyte antibodies including anti-human leucocyte antigen (anti- HLA) antibodies (class I and class II) and anti-human neutrophil antigen (anti-HNA) antibodies ( HNA-1, -2 and -3) present in the blood products are responsible for transfusion-related acute lung injury ( TRALI). Therefore, selection of blood products exclusive of anti- HLA and anti- HNA antibodies may lower the risk of TRALI reaction. However, the prevalence of leucocyte antibodies among blood donors in China is currently not known. Study design and methods Blood samples were collected from 454 male and 560 female donors (143 nulliparous and 417 multiparous female). HLA class I and II antibodies were analyzed by bead assays. Anti- HNA-1 and -2 antibodies were screened by the LABScreen assay (One Lambda Inc.), and HNA-3 were detected by antigen capture assay, and confirmed by the granulocyte agglutination test ( GAT). Results Screening of the total cohort showed higher prevalence of HLA antibodies in female compared with male donors (19·64 vs 4·63%). We found antibodies against HLA class I (13·21%) and HLA class II (11·43%) in 560 female donors. The most frequent antibodies against HLA class I and II in parous females ( n = 69) reacted with were A*11 (28·81%), B*07 (42·37%), Cw*07 (20·34%) and DRB1*04 (40·43%) molecules. Among 778 donors (randomly selected from 1014 donors), we found three donors with neutrophil reactive antibodies, two against HNA-2 and one without known specificity. Anti- HNA-3 antibodies were not found so far. Conclusion In this study, we found alloimmunization against HLA class I, II and HNA in 4·63, 24·70 and 0·39%, respectively, in our female blood donors, indicating that the use of plasma containing blood products from parous female blood donors without HLA antibodies pre-testing may increase the risk of TRALI reaction. Although immunization against HNA seems to be a rare event in China, further observation is necessary to decide the necessity of HNA antibodies screening in our blood donors. [ABSTRACT FROM AUTHOR]

Background and purpose Using an innovative chemical approach, peptide welding technology ( PWT), a tetrabranched derivative of nociceptin/orphanin FQ ( N/ OFQ) has been generated and pharmacologically characterized. Both in vitro and in vivo PWT2- N/ OFQ displayed the same pharmacological profile to the natural ligand. It was more potent and produced longer-lasting effects. The aim of the present study was to investigate the spinal effects of PWT2- N/ OFQ in nociceptive and neuropathic pain models in mice and non-human primates. Experimental Approach Tail withdrawal assay in mice and monkeys was used as a nociceptive pain model and mechanical threshold in mice subjected to chronic constriction injury was used as a neuropathic pain model. The antinociceptive effects of spinally administered N/ OFQ and PWT2- N/ OFQ were assessed in these models. Key Results PWT2- N/ OFQ mimicked the spinal antinociceptive effects of N/ OFQ both in nociceptive and neuropathic pain models in mice as well as in non-human primates displaying 40-fold higher potency and a markedly prolonged duration of action. The effects of N/ OFQ and PWT2- N/ OFQ were sensitive to the N/ OFQ receptor ( NOP) antagonist SB-612111, but not to opioid receptor antagonists. Conclusions and Implications The present study has demonstrated that PWT2- N/ OFQ mimicked the antinociceptive effects of the natural peptide in rodents and non-human primates acting as a potent and longer-lasting NOP-selective agonist. More generally, PWT derivatives of biologically active peptides can be viewed as innovative pharmacological tools for investigating those conditions and states in which selective and prolonged receptor stimulation promotes beneficial effects. [ABSTRACT FROM AUTHOR]

Background and Purpose Nociceptin/orphanin FQ ( N/ OFQ) peptide ( NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects of centrally administered ligands on regulating pain and itch in non-human primates. In particular, nociceptive thresholds affected by intracisternal N/OFQ were compared with those of morphine and substance P, known to provide analgesia and mediate hyperalgesia, respectively, in humans. Experimental Approach Intrathecal catheters were installed to allow intracisternal and lumbar intrathecal administration in awake and unanaesthetized rhesus monkeys. Nociceptive responses were measured using the warm water tail-withdrawal assay. Itch scratching responses were scored from videotapes recording behavioural activities of monkeys in their home cages. Antagonist studies were conducted to validate the receptor mechanisms underlying intracisternally elicited behavioural responses. Key Results Intracisternal morphine (100 nmol) elicited more head scratches than those after intrathecal morphine. Distinct dermatomal scratching locations between the two routes suggest a corresponding activation of supraspinal and spinal μ receptors. Unlike intracisternal substance P, which induced hyperalgesia, intracisternal N/OFQ (100 nmol) produced antinociceptive effects mediated by NOP receptors. Neither peptide increased scratching responses. Conclusions and Implications Taken together, these results demonstrated differential actions of ligands in the primate supraspinal region in regulating pain and itch. This study not only improves scientific understanding of the N/OFQ-NOP receptor system in pain processing but also supports the therapeutic potential of NOP-related ligands as analgesics. [ABSTRACT FROM AUTHOR]

The Gangdese magmatic arc, southeastern Tibet, was built by mantle-derived magma accretion and juvenile crustal growth during the Mesozoic to Early Cenozoic northward subduction of the Neo-Tethyan oceanic slab beneath the Eurasian continent. The petrological and geochronological data reveal that the lower crust of the southeastern Gangdese arc experienced Oligocene reworking by metamorphism, anatexis and magmatism after the India and Asia collision. The post-collisional metamorphic and migmatitic rocks formed at 34-26 Ma and 28-26 Ma respectively. Meta-granitoids have protolith ages of 65-38 Ma. Inherited detrital zircon from metasedimentary rocks has highly variable ages ranging from 2708 to 37 Ma. These rocks underwent post-collisional amphibolite facies metamorphism and coeval anatexis under P-T conditions of ~710-760 °C and ~12 kbar with geothermal gradients of 18-20 °C km −1, indicating a distinct crustal thickening process. Crustal shortening, thickening and possible subduction erosion due to the continental collision and ongoing convergence resulted in high- P metamorphic and anatectic reworking of the magmatic and sedimentary rocks of the deep Gangdese arc. This study provides a typical example of the reworking of juvenile and ancient continental crust during active collisional orogeny. [ABSTRACT FROM AUTHOR]

A two-period cross-over study was carried to investigate the pharmacokinetics ( PK) and ex-vivo pharmacodynamics ( PD) of cefquinome when administrated intravenously ( IV) and intramuscularly ( IM) in seven healthy dogs at a dose of 2 mg/kg of body weight. Serum concentrations were determined by HPLC-MS/MS assay and cefquinome concentration vs. time data after IV and IM were best fit to a two-compartment open model. Cefquinome mean values of area under concentration-time curve ( AUC) were 5.15 μg·h/mL for IV dose and 4.59 μg·h/mL for IM dose. Distribution half-lives and elimination half-lives after IV dose and IM dose were 0.27 and 0.44 h, 1.53 and 1.94 h, respectively. Values of total body clearance ( ClB) and volume of distribution at steady-state ( Vss) were 0.49 L·kg/h and 0.81 L/kg, respectively. After IM dose, Cmax was 2.53 μg/mL and the bioavailability was 89.13%. For PD profile, the determined MIC and MBC values against K. pneumonia were 0.030 and 0.060 μg/mL in MHB and 0.032 and 0.064 μg/mL in serum. The ex vivo time-kill curves also were established in serum. In conjunction with the data on MIC, MBC values and the ex vivo bactericidal activity in serum, the present results allowed prediction that a single cefquinome dosage of 2 mg/kg may be effective in dogs against K. pneumonia infection. [ABSTRACT FROM AUTHOR]

The fluoroquinolone antimicrobial drug marbofloxacin was administered to yellow cattle intravenously and intramuscularly at a dose of 2 mg/kg of body weight in a two-period crossover study. The pharmacokinetic properties of marbofloxacin in serum, inflamed tissue-cage fluid (exudate), and noninflamed tissue-cage fluid (transudate) were studied by using a tissue-cage model. The in vitro and ex vivo activities of marbofloxacin in serum, exudate, and transudate against a pathogenic strain of Pasteurella multocida ( P. multocida) were determined. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the area under the curve ( AUC)/ MIC for serum, exudate, and transudate of 155.75, 153.00, and 138.88, respectively, after intravenous dosing and 160.50, 151.00, and 137.63, respectively, after intramuscular dosing. After intramuscular dosing, the maximum concentration/ MIC ratios for serum, exudate, and transudate were 21.13, 9.13, and 8.38, respectively. The ex vivo growth inhibition data after intramuscular dosing were fitted to the inhibitory sigmoid Emax equation to provide the values of AUC/ MIC required to produce bacteriostasis, bactericidal activity, and elimination of bacteria. The respective values for serum were 17.25, 31.29, and 109.62, and slightly lower values were obtained for transudate and exudate. It is proposed that these findings might be used with MIC50 or MIC90 data to provide a rational approach to the design of dosage schedules which optimize efficacy in respect of bacteriological as well as clinical cures. [ABSTRACT FROM AUTHOR]

The cephalosporin antimicrobial drug cefquinome was administered to yellow cattle intravenously (i.v.) and intramuscularly (i.m.) at a dose of 1 mg/kg of body weight in a two-period crossover study. The pharmacokinetic ( PK) properties of cefquinome in serum, inflamed tissue-cage fluid (exudate), and noninflamed tissue-cage fluid (transudate) were studied using a tissue-cage model. The in vitro and ex vivo activities of cefquinome in serum, exudate, and transudate against a pathogenic strain of Pasteurella multocida ( P. multocida) were determined. A concentration-independent antimicrobial activity of cefquinome was confirmed for levels lower than 4 × MIC. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the time that drug levels remain above the MIC ( T > MIC) in serum was 14.10 h after intravenous and 14.46 h after intramuscular dosing, indicating a likely high level of effectiveness in clinical infections caused by P. multocida of MIC 0.04 μg/mL or less. These data may be used as a rational basis for setting dosing schedules, which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms. [ABSTRACT FROM AUTHOR]

A new ultrahigh-energy-resolution and wide-energy-range soft X-ray beamline has been designed and is under construction at the Shanghai Synchrotron Radiation Facility. The beamline has two branches: one dedicated to angle-resolved photoemission spectroscopy (ARPES) and the other to photoelectron emission microscopy (PEEM). The two branches share the same plane-grating monochromator, which is equipped with four variable-line-spacing gratings and covers the 20-2000 eV energy range. Two elliptically polarized undulators are employed to provide photons with variable polarization, linear in every inclination and circular. The expected energy resolution is approximately 10 meVat 1000 eV with a flux of more than 3 x 1010 photons s-1 at the ARPES sample positions. The refocusing of both branches is based on Kirkpatrick-Baez pairs. The expected spot sizes when using a 10 µm exit slit are 15 µm x 5 µm (horizontal x vertical FWHM) at the ARPES station and 10 µm x 5 µm (horizontal x vertical FWHM) at the PEEM station. The use of plane optical elements upstream of the exit slit, a variable-line-spacing grating and a pre-mirror in the monochromator that allows the influence of the thermal deformation to be eliminated are essential for achieving the ultrahigh-energy resolution. [ABSTRACT FROM AUTHOR]

The plasma and tissue pharmacokinetics of marbofloxacin in chickens experimentally infected with Mycoplasma gallisepticum and Escherichia coli were studied. Marbofloxacin was given to 66 infected chickens by oral administration at a dosage of 5 mg/kg b.w., once a day for three days. Plasma, brain, kidney, liver, lung, muscle and trachea were collected and marbofloxacin concentrations were analyzed by a high performance liquid chromatography method. In the infected chickens, maximal marbofloxacin concentrations in plasma, brain, kidney, liver, lung, muscle and trachea were 1.84, 1.33, 7.35, 5.61, 3.12, 2.98, and 4.51 g/mL (g); the elimination half-lives of marbofloxacin were 6.8, 2.74, 9.31, 8.45, 9.55, 11.53 and 5.46 h for plasma, brain, kidney, liver, lung, muscle and trachea, respectively. AUC were calculated to be 9.68, 8.04, 45.1, 27.03, 20.56, 19.47, and 32.68 μg/mL (g) ·h for plasma, brain, kidney, liver, lung, muscle and trachea, respectively. Marbofloxacin concentration in tissues except for brain exceeded marbofloxacin concentration in plasma, with AUCtissue/AUCplasma ranging from 2.01 to 4.66 and Peaktissue/Peakplasma ranging from 1.62 to 3.99. The results showed that a marbofloxacin dosage of 5 mg/kg administered orally at 24 h intervals may provide successful treatment of chicken with MG and E. coli infection. [ABSTRACT FROM AUTHOR]

The article reports the study on the nonsteroidal anti-inflammatory drug (NSAID) Flunixin meglumine (FLM) to cure respiratory diseases and relieve pains in broiler chickens in China. It uses 30 broiler chickens which divided into three groups, the first and second group was treated with FLM and doxycycline hyclate via left leg vein while the third group was treated via veins on both sides. In conclusion, doxycycline and FLM could relieve inflammation, infection and pain on chickens.

Ghrelin is a growth hormone secretagogue peptide and has been recognized as an orexigenic factor. To investigate relationship between cord ghrelin and anthropometric and metabolic indices, we measured cord ghrelin in large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) neonates and examined whether cord ghrelin levels were correlated to concentrations of cord blood glucose, insulin, lipid and maternal ghrelin. Fifty-five singletons born at term and their mothers were investigated in this study. Maternal venous blood samples were collected before delivery. Plasma concentrations of ghrelin, insulin, glucose, total cholesterol, triacylglycerol (TG), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol were measured in cord blood sampled at birth. The results show that the concentrations of cord ghrelin are significantly lower in LGA neonates. There is a positive correlation between cord ghrelin levels and maternal ghrelin levels. Negative correlations are found between cord ghrelin levels and gestational age, the concentrations of cord glucose, insulin, TG and LDL. Multivariate regression analyses show that birth weight ( r2 = 0.674, β = −0.548, P < 0.001) was the predictor correlating with ghrelin levels. In conclusion, LGA neonates have lower cord ghrelin concentrations than AGA neonates. [ABSTRACT FROM AUTHOR]

Background and Purpose: We hypothesized that proteinase-activated receptor-2 (PAR2)-mediated vasorelaxation in murine aorta tissue can be due in part to the release of adipocyte-derived relaxing factors (ADRFs).Experimental Approach: Aortic rings from obese TallyHo and C57Bl6 intact or PAR2-null mice either without or with perivascular adipose tissue (PVAT) were contracted with phenylephrine and relaxation responses to PAR2-selective activating peptides (PAR2-APs: SLIGRL-NH(2) and 2-furoyl-LIGRLO-NH(2) ), trypsin and to PAR2-inactive peptides (LRGILS-NH(2) , 2-furoyl-OLRGIL-NH(2) and LSIGRL-NH(2) ) were measured. Relaxation was monitored in the absence or presence of inhibitors that either alone or in combination were previously shown to inhibit ADRF-mediated responses: L-NAME (NOS), indomethacin (COX), ODQ (guanylate cyclase), catalase (H(2) O(2) ) and the K(+) channel-targeted reagents, apamin, charybdotoxin, 4-aminopyridine and glibenclamide.Key Results: Endothelium-intact PVAT-free preparations did not respond to PAR2-inactive peptides (LRGILS-NH(2) , LSIGRL-NH(2) , 2-furoyl-OLRGIL-NH(2) ), whereas active PAR2-APs (SLIGRL-NH(2) ; 2-furoyl-LIGRLO-NH(2) ) caused an L-NAME-inhibited relaxation. However, in PVAT-containing preparations treated with L-NAME/ODQ/indomethacin together, both PAR2-APs and trypsin caused relaxant responses in PAR2-intact, but not PAR2-null-derived tissues. The PAR2-induced PVAT-dependent relaxation (SLIGRL-NH(2) ) persisted in the presence of apamin plus charybdotoxin, 4-aminopyridine and glibenclamide, but was blocked by catalase, implicating a role for H(2) O(2) . Surprisingly, the PAR2-inactive peptides, LRGILS-NH(2) and 2-furoyl-OLRGIL-NH(2) (but not LSIGRL-NH(2) ), caused relaxation in PVAT-containing preparations from both PAR2-null and PAR2-intact (C57Bl, TallyHo) mice. The LRGILS-NH(2) -induced relaxation was distinct from the PAR2 response, being blocked by 4-aminopyridine, but not catalase.Conclusions: Distinct ADRFs that may modulate vascular tone in pathophysiological settings can be released from murine PVAT by both PAR2-dependent and PAR2-independent mechanisms. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are stably present in human serum. The relationship between circulating miRNAs and hepatitis B virus (HBV) infected liver disease has not been previously reported. Applied Biosystems array-based miRNA expression profiling was performed on pooled sera obtained from identified groups of chronic asymptomatic carriers (ASC), patients with chronic hepatitis B (CHB) and HBV-associated acute-on-chronic liver failure (ACLF), as well as healthy controls (HC). Nine miRNAs were verified in more clinical samples by RT-PCR. The correlation between miRNAs expression and the relationship between miRNA levels and clinical characteristics was analysed. Results showed that circulating miRNAs were detected in all disease and control samples, and their numbers increased with symptom severity, from 37 in HC, 77 in ASC, 101 in CHB, to 135 in ACLF. The expression levels of most miRNAs were also up-regulated in HBV-infected patients when compared to HC. Expression of the liver-specific miR-122 was significantly up-regulated in HBV-infected patients. Concomitant regulation of miRNAs not in clusters was disrupted by HBV infection. However, such disruption was not observed for miRNAs in paralogous clusters. Furthermore, the level of miRNAs in the CHB serum was up-regulated most in hepatitis B e antigen-positive patients. The expression levels of miR-122 and miR-194 correlated negatively with the age of patients with CHB or ACLF. Functional analysis showed that miR-122 could inhibit HBV replication in Huh7 and HepG2 cells. In all, our study revealed that a number of miRNAs were differentially expressed during HBV infection and underscored the potential importance of miR-122 in the infection process. [ABSTRACT FROM AUTHOR]

The article discusses the pharmacokinetics and tissue distribution of danofloxacin in healthy chickens and chickens infected with Pasteurella multocida. It refers danofloxacin as a fluoroquinolone group's synthetic antibiotic use for veterinary medicine. The study found no differences in the elimination half-life of danofloxacin in healthy and infected chickens. It concludes that infected chickens have lower danofloxacin peak concentrations in plasma and tissues than those of healthy chickens.

The article presents a study which provides a better understanding on the pharmacokinetics of marbofloxacin in pig plasma and tissue cage fluids. It says that marbofloxacin is applied through intravenous, intramuscular and oral administration, in which tissue cages are injected on either side of the neck of the pigs. The results show that the ability of marbofloxacin to spread into extravascular tissues efficiently is effective for treating infections of the skin and soft tissues in animals.

In order to improve the performance of ZnO-based solar cells, highly-ordered hierarchical ZnO nanostructures were design and fabricated. The hierarchical nanostructures were grown on FTO (fluorine doped tin oxide, SnO2:F) glass substrates via a facile, low-temperature, and low-cost chemical route. The morphology and structure of the obtained products has been confirmed by field-emission scanning electron microscopy and X-ray diffraction measurements. The performance investigation of the prepared dye-sensitized solar cells (DSSCs) demonstrates that the hierarchical ZnO nanostructure-based solar cell shows a higher short-circuit current density compared with the ZnO nanowire counterpart. The enhanced current density may be due to the fact that the surface area of the hierarchical nanostructures is increased. These results indicate that hierarchical ZnO nanostructures are more suitable for the application as photoelectrode of DSSCs. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Three normalized cDNA libraries were constructed, two of which were constructed from reproductive tissues ovary and testis, and the other one from pooled immune tissues including head kidney, intestine, liver and spleen. A total of 10 542 clones were sequenced generating 10 128 expressed sequence tags (ESTs). Cluster analysis indicated a total of 5808 unique sequences including 1712 contigs and 4096 singletons. A total of 4249 (73%) of the unique ESTs had significant hits to the non-redundant protein database, 2253 of which were annotated using Gene Ontology (GO) terms. A total of 311 microsatellites (with 246 having sufficient flanking sequences for primer design) and 6294 putative SNPs were identified. These genome resources provide the material basis for future microarray development, marker validation and genetic linkage and QTL analysis. [ABSTRACT FROM AUTHOR]

The article presents a study on specific major histocompatibility complex (MHC) class II B alleles associated with resistance to the bacteria Edwardsiella tarda in turbot, Psetta maxima. For the study, bacteria were withdrawn from the abdominal cavity of diseased cultured turbot. A single clone was characterized as Edwardsiella tarda by 16S recombinant deoxyribonucleic acid (rDNA) sequence alignment and this clone was cultured and used for challenge test. The procedures of the study have been described. It has been concluded that the MHC II B gene in turbot is highly polymorphic. It is also concluded that the alleles Scma-DBB1*04 and Scma-DBB1*10 are associated with tarda susceptibility while Scma-DBB2*01 is associated with resistance.

A new method for recording both fluorescence and cryo-EM images of small bacterial cells was developed and used to identify chemoreceptor arrays in cryotomograms of intact Caulobacter crescentus cells. We show that in wild-type cells preserved in a near-native state, the chemoreceptors are hexagonally packed with a lattice spacing of 12 nm, just a few tens of nanometers away from the flagellar motor that they control. The arrays were always found on the convex side of the cell, further demonstrating that Caulobacter cells maintain dorsal/ventral as well as anterior/posterior asymmetry. Placing the known crystal structure of a trimer of receptor dimers at each vertex of the lattice accounts well for the density and agrees with other constraints. Based on this model for the arrangement of receptors, there are between one and two thousand receptors per array. [ABSTRACT FROM AUTHOR]

Pharmacokinetics of difloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of five (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analyzed by a compartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t1/2 β) were 17.14 ± 4.14, 25.79 ± 8.10, 16.67 ± 4.04 (pigs) and 6.11 ± 1.50, 5.64 ± 0.74, 8.20 ± 3.12 h (broilers), respectively. After single i.m. and p.o. administration, difloxacin was rapidly absorbed, with peak plasma concentrations (Cmax) of 1.77 ± 0.66, 2.29 ± 0.85 (pigs) and 2.51 ± 0.36, 1.00 ± 0.21 μg/mL (broilers) attained at tmax of 1.29 ± 0.26, 1.41 ± 0.88 (pigs) and 0.86 ± 0.4, 4.34 ± 2.40 h (broilers), respectively. Bioavailabilities (F) were (95.3 ± 28.9)% and (105.7 ± 37.1)% (pigs) and (77.0 ± 11.8)% and (54.2 ± 12.6)% (broilers) after i.m. and p.o. doses, respectively. Apparent distribution volumes(Vd(area)) of 4.91 ± 1.88 and 3.10 ± 0.67 L/kg and total body clearances(ClB) of 0.20 ± 0.06 and 0.37 ± 0.10 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), the half-lives of both absorption and distribution(t1/2ka, t1/2 α) were also determined. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 5 mg/kg given intramuscularly every 24 h in pigs, or administered orally every 24 h at the dosage of 10 mg/kg in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 μg/mL and <0.1 μg/mL respectively. [ABSTRACT FROM AUTHOR]

This study was performed in 105 ill cows to determine the best practical individualized dose of enrofloxacin after i.m. (2.5 mg/kg) single-dose administration. Samples were collected from each cow at random time to ensure the percentage of samples distributed equally in the absorption phase, distribution phase, and elimination phase of the drug. Drug concentrations were determined by high-performance liquid chromatography with fluorometric detector, analyzed by population pharmacokinetic (PPK) modeling with NONMEM. The concentration–time data for enrofloxacin in plasma and ciprofloxacin were fitted to the one-compartment model with first-order absorption and elimination. The final covariate model indicated that body weight and daily milk productions have significant influence on clearance (CL) of enrofloxacin and ciprofloxacin, and the volume ( V) of distribution of enrofloxacin. The typical PPK parameters were Ka = 3.33 h−1, CL = 1.25 L/h/kg, and V = 2.98 L/kg of enrofloxacin, and the interindividual variability for CL and V were 20.2% and 24.3%, respectively, the population mean estimates of Ka, CL, and V for ciprofloxacin were 1.12 h−1, 2.36 L/h/kg, 8.20 L/kg, respectively, and their interindividual variability was 36.9%, 15.8% and 14.1%, respectively. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to determine antimicrobial usage in paediatric intensive care units (PICUs) in China. Methods: Data were equally collected from 540 charts of PICUs in the three Chinese tertiary teaching children hospitals in 2006. The data included demographic, clinical data and those on antimicrobial usage and results of microbiological examinations. Results: Of the 540 cases, 524 (94.7%) patients received at least one antimicrobial agent. The main treatment started empirically in 387 (71.6%). The third-generation cephalosporins were the major antimicrobials used in all participating hospitals, accounting for 227 (31%). Bacteria were isolated from 48%, 68% and 59% of the three PICUs. Six common pathogens accounted for more than 75% of the isolated bacteria. The rates of Escherichia coli isolates resistant to cefotaxime were 73.8%, 58.3% and 49.2%, respectively, with the rate being higher in H1 than in H2 and H3 (both p < 0.01). Conclusions: Irrational use of antimicrobials exists in clinical practice of PICUs in China. It is recommended that antimicrobial usage should be guided by bacterial isolation and antimicrobial susceptibility tests in order to select correct antimicrobials and to prevent emergency of drug-resistant strains in PICUs. [ABSTRACT FROM AUTHOR]

The major structural elements of retroviruses are contained in a single polyprotein, Gag, which in human immunodeficiency virus type 1 (HIV-1) comprises the MA, CA, spacer peptide 1 (SP1), NC, SP2, and p6 polypeptides. In the immature HIV-1 virion, the domains of Gag are arranged radially with the N-terminal MA domain at the membrane and C-terminal NC-SP2-p6 region nearest to the center. Here, we report the three-dimensional structures of individual immature HIV-1 virions, as obtained by electron cryotomography. The concentric shells of the Gag polyprotein are clearly visible, and radial projections of the different Gag layers reveal patches of hexagonal order within the CA and SP1 shells. Averaging well-ordered unit cells leads to a model in which each CA hexamer is stabilized by a bundle of six SP1 helices. This model suggests why the SP1 spacer is essential for assembly of the Gag lattice and how cleavage between SP1 and CA acts as a structural switch controlling maturation. [ABSTRACT FROM AUTHOR]

This study focused on the crack-healing behaviour of three commercial Al2O3–ceramic-matrix composites: TiCP/Al2O3, ZrO2/Al2O3 and SiCW/Al2O3. Vickers indentation was used to introduce surface flaws with different loads of 49, 98 and 196 N. Then the cracked specimens were annealed in air for 1 h at 1000, 1200 and 1400 °C. The annealing treatment was also conducted at 1200 °C in vacuum for 1 h. Results showed that the annealing treatments increased the indentation strength, but the extent of the increase was different. When annealed in air, the main crack-healing mechanism of TiCP/Al2O3 and SiCW/Al2O3 composites was chemical reaction. When annealed in vacuum, stress relaxation caused much less strength recovery. The main crack-healing mechanism of ZrO2/Al2O3 was the existence of low melting eutectic and the rearrangement of grains caused by ZrO2(m)→ ZrO2(t) transformation in the crack-opening process zone. The effects of annealing temperature, atmosphere and indentation load on the degree of strength recovery were all related to the crack-healing mechanisms. [ABSTRACT FROM AUTHOR]

ABSTRACT A (high strain) low-cycle fatigue (LCF) life prediction model of ultrafine-grained (UFG) metals has been proposed. The microstructure of a UFG metal is treated as a two-phase ‘composite’ consisting of the ‘soft’ matrix (all the grain interiors) and the ‘hard’ reinforcement (all the grain boundaries). The dislocation strengthening of the grain interiors is considered as the major strengthening mechanism in the case of UFG metals. The proposed model is based upon the assumption that there is a fatigue-damaged zone ahead of the crack tip within which the actual degradation of the UFG metal takes place. In high-strain LCF conditions, the fatigue-damaged zone is described as the region in which the local cyclic stress level approaches the ultimate tensile strength of the UFG metal, with the plastic strain localization caused by a dislocation sliding-off process within it. The fatigue crack growth rate is directly correlated to the range of the crack-tip opening displacement. The empirical Coffin–Manson and Basquin relationships are derived theoretically and compared with experimental fatigue data obtained on UFG copper (99.99%) at room temperature under both strain and stress control. Good agreement is found between the model and the experimental data. It is remarkable that, although the model is essentially formulated for high strains (LCF), it is also found to be applicable at low strains in the high-cycle fatigue (HCF) regime. [ABSTRACT FROM AUTHOR]

Pharmacokinetics of sarafloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of 5 (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analysed by a noncompartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t1/2β) were 3.37 ± 0.46, 4.66 ± 1.34, 7.20 ± 1.92 (pigs) and 2.53 ± 0.82, 6.81 ± 2.04, 3.89 ± 1.19 h (broilers), respectively. After i.m. and p.o. doses, bioavailabilities (F) were 81.8 ± 9.8 and 42.6 ± 8.2% (pigs) and 72.1 ± 8.1 and 59.6 ± 13.8% (broilers), respectively. Steady-state distribution volumes (Vd(ss)) of 1.92 ± 0.27 and 3.40 ± 1.26 L/kg and total body clearances (ClB) of 0.51 ± 0.03 and 1.20 ± 0.20 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), mean residence times (MRT), and mean absorption times (MAT) were also determined. Sarafloxacin was demonstrated to be more rapidly absorbed, more extensively distributed, and more quickly eliminated in broilers than in pigs. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 10 mg/kg given intramuscularly every 12 h in pigs, or administered orally every 8 h in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 μg/mL. [ABSTRACT FROM AUTHOR]

A statistical model of fatigue damage evolution has been developed for particulate-reinforced metal-matrix-composites (MMCs) by taking into considerations both the initial damage distribution and the effect of particulate reinforcement on fatigue damage development. The growth of microscopically fatigue-damaged regions in particulate-reinforced MMCs is considered as a stochastic process, and both the non-equilibrium statistical method and minimum strength principle are used to establish the evolution equation of fatigue damage. The fatigue damage evolution equation developed in the present study characterizes not only the kinetic process of fatigue damage evolution but also sets up the relationship between the mechanism of fatigue damage growth of the microscopically damaged regions and the result of fatigue damage, i.e. degradation of mechanical properties of particulate-reinforced MMCs. A new expression for calculating the cumulative fatigue damage and a new formula for predicting the average fatigue strength of the particulate-reinforced MMCs are derived. Experimental data of 2080Al/SiCp composites are analysed and compared with results obtained with the present model. It is shown that the experimental results can be described well by the calculations. [ABSTRACT FROM AUTHOR]

A finite-difference method (FDM) combined with an analytical truncation boundary is proposed for the analysis of an H-plane waveguide Y-junction circulator. The approach is based on a field component wave equation in the cylindrical coordinate and analytical field distributions in rectangular waveguides. A boundary field equation for the ferrite/dielectric interface is derived. The numerical results of the characteristics of H-plane waveguide Y-junction circulators with lossless or lossy ferrite posts and composite ferrite posts are calculated by the present method, and good agreement with previously published experimental and theoretical results has been achieved. ©1999 John Wiley & Sons, Inc. Microwave Opt Technol Lett 20: 414–422, 1999. [ABSTRACT FROM AUTHOR]

Determines the level of Actinomyces pyogenes specific antibodies in bovine blood samples by an enzyme-linked immunosorbent assay. Isolation of A. pyogenes; Extracellular products of A. pyogenes; Analysis of A. pyogenes vaccines.

A novel shielded periodic meander line is presented. Its dispersion characteristics are formulated in terms of a rigorous, hybrid-mode representation and Floquet theorem. Some numerical results are included and good agreements compared with other available data are observed. Finally, a quarter-wave rectangular cavity with a shielded meander line is designed. [ABSTRACT FROM AUTHOR]

A new method far analyzing a millimeter-wave H-piane waveguide Y-junction circulator with a partial height ferrite post is presented. Simple formulas are developed for determining the center frequency of the circulator and the length of the ferrite rod. The lowest made of operation is not unique and is dependent on the length of the ferrite post. Based on the newly derived formulas, several broadband 3-mm circulators have been designed, assembled, and tented. Good agreement between the analytically obtained performance and experimental results is observed. [ABSTRACT FROM AUTHOR]

Binding of 125I-labelled α2-macroglobulin (α2M) to Actinomyces pyogenes was investigated. The binding of α2M proved to be time dependent, saturable, and could be inhibited by unlabelled α2M, but not by fibrinogen, haptoglobin, fibronectin, or albumin. The α2M binding site was sensitive to treatment with proteolytic enzymes and heat, indicating its protein nature. The dissociation constant (Kd) was 4.447 times 10−9 M, and the number of binding sites per bacterial cell was calculated to be 5200. The kinetic analysis indicated an homogenous population of binding sites. Binding of α2M to the surface of A. pyogenes had no significant influence on the phagocytosis of the bacteria by polymorphonuclear leucocytes. [ABSTRACT FROM AUTHOR]

A haemolysin produced by Actinomyces pyogenes ATCC 8164 was purified from culture supernatant by ammonium sulphate and polyethylene glycol precipitation, ion-exchange chromatography on DEAE-Sephacel, and fast-protein-liquid-chromatography on Superose 12 prep grade. The purified haemolysin, designated as pyolysin, displayed a single band on poly-acrylamide gel electrophoresis, indicating a molecular weight of 55000. Additionally, using gel filtration, the same molecular weight was estimated. Further studies of the eluate of ion-exchange chromatography using isoelectric focusing also revealed a single protein band at pH 9.38 with haemolytic activity. A specific antiserum produced against pyolysin inhibited the haemolytic activity. The purity of the isolated protein was also determined by Western Blot analysis with antiserum obtained from a cow inoculated with culture supernatant from A. pyogenes and Peptococcus indolicus. The isolated pyolysin appeared to be heat-labile and displayed cytotoxic effects on poly-morphonuclear leucocytes and on pTK2 kidney cells. [ABSTRACT FROM AUTHOR]