\n\nIn the future, we foresee new discoveries related to these interesting nanoalloys. HSP990 mw In particular, colloidal semiconductor nanoalloys that exhibit composition-dependent magnetic properties have yet to be reported. Further studies of the alloying mechanism are also needed to develop improved synthetic strategies for the preparation
of these alloyed nanomaterials.”
“We evaluated the kinetic culture characteristics of the microalgae Cyanobium sp. grown in vertical tubular photobioreactor in semicontinuous mode. Cultivation was carried out in vertical tubular photobioreactor for 2 L, in 57 d, at 30 degrees C, 3200 Lux, and 12 h light/dark photoperiod. The maximum specific growth rate was found as 0.127 d(-1), when the culture had blend concentration of 1.0 g L(-1), renewal rate of 50%, and sodium bicarbonate concentration of 1.0 g L(-1). The maximum values of productivity (0.071 g L(-1) d(-1)) and number of cycles (10) were observed in blend concentration of 1.0
g L(-1), renewal rate of 30%, and bicarbonate concentration find more of 1.0 g L(-1). The results showed the potential of semicontinuous cultivation of Cyanobium sp. in closed tubular bioreactor, combining factors such as blend concentration, renewal rate, and sodium bicarbonate concentration. 2011 Published by Elsevier Ltd.”
“Pyruvate orthophosphate dikinase (PPDK) is a key enzyme in C4 photosynthesis and is also found in C3 plants. It is post-translationally modified by the PPDK regulatory protein (RP) that possesses both kinase and phosphotransferase activities. Phosphorylation and dephosphorylation of PPDK lead to inactivation and activation respectively. Arabidopsis thaliana contains two genes that encode chloroplastic (RP1) and cytosolic (RP2)
isoforms of RP, and although RP1 has both kinase and phosphotransferase activities, to date RP2 has only been shown to act PF-00299804 nmr as a kinase. Here we demonstrate that RP2 is able to catalyse the dephosphorylation of PPDK, although at a slower rate than RP1 under the conditions of our assay. From yeast two-hybrid analysis we propose that RP1 binds to the central catalytic domain of PPDK, and that additional regions towards the carboxy and amino termini are required for a stable interaction between RP2 and PPDK. For 21 highly conserved amino acids in RP1, mutation of 15 of these reduced kinase and phosphotransferase activity, while mutation of six residues had no impact on either activity. We found no mutant in which only one activity was abolished. However, in some chimaeric fusions that comprised the amino and carboxy termini of RP1 and RP2 respectively, the kinase reaction was severely compromised but phosphotransferase activity remained unaffected. These findings are consistent with the findings that both RP1 and RP2 modulate reversibly the activity of PPDK, and possess one bifunctional active site or two separate sites in close proximity.
Awareness of risk factors was no greater in respondents identified as having chronic kidney disease (CKD). A third of respondents with CKD recalled having undergone a test of kidney function within the
previous 2 years, while another third replied they had never had their kidney function tested. Of participants with previously diagnosed diabetes or treated hypertension, 54.1% and 32.0%, respectively, reported having their kidney function tested within the previous 2 years.\n\nConclusions: Knowledge ML323 in vivo of risk factors for kidney disease and recall of kidney function testing were both limited, even among subgroups of the cohort who were at greatest risk of CKD. Prevention efforts may benefit from public and patient education to improve recognition of risk factors for CKD.”
“Therapeutic management in pregnant patients with heart failure still remains a challenge, even though in most pregnant women with cardiac diseases an outcome is good. A 32-year-old woman, 17 weeks pregnant, was admitted to hospital with heart failure
(HF) NYHA class III/IV. Echocardiography revealed enlarged LV, LVEF 13%, significant mitral insufficiency and pulmonary hypertension. The patient wished to continue VX-680 molecular weight the pregnancy. In a life-threatening condition, metoprolol, enalapril, spironolactone (for 5 days), furosemide, and digitalis were administered. Enalapril was continued for 42 days. Then the patient was switched to a dihydralazine and isosorbide mononitrate regimen. The fetus was controlled ultrasonographically. In the 19th week of pregnancy, the patient’s condition improved (NYHA class II, LVEF 23%). The patient experienced 2 more episodes of HF exacerbation. In the 26th week of pregnancy, in a primary prevention
of sudden cardiac death and because of 2nd-degree AV block, an ICD was implanted. In the 32nd week of pregnancy a cesarean section was performed. A male infant was delivered. The patient made a good recovery and was discharged on the 7th postoperative day. The newborn was check details discharged after 4 weeks, in good general condition. At 1-year follow-up the patient presented NYHA class II.”
“Background: Loss of medullary sympathoexcitatory neurons may contribute to baroreflex failure, leading to orthostatic hypotension in multiple-system atrophy (MSA). The cardiovascular responses to chemoreflex activation in MSA have not been explored to date.\n\nObjectives: To determine whether ventilatory and cardiovascular responses to hypercapnia and hypoxia during wakefulness are systematically impaired in MSA.\n\nDesign: Case-control study.\n\nSetting: Mayo Clinic, Rochester, Minnesota.\n\nPatients: Sixteen patients with probable MSA (cases) and 14 age-matched control subjects (controls).
\n\nResults: The Shiraz population in the aforementioned period of time was approximately 1,255,955, and mean Jewish population was 5784. There were 356 non-Jewish and 15 Jewish
cases with intracranial meningioma. The relative risk for development of meningioma in Jewish population was 9.10 (95% CI: 4.81-14.01; P < 0.01). The prevalence of meningioma in Jewish population in our series was 259 (95% CI: 128-390) per 100,000 population.\n\nConclusions: selleck kinase inhibitor Our study showed an increased risk of intracranial meningioma among those of Jewish race in this specific region. Meningioma risk was elevated almost 9-fold among Jewish residents of the city of Shiraz. Clearly established environmental risk factors were not found to cause such a higher risk in this study. Our findings indicate the influence of genetic factors in the higher risk for meningioma among jews.”
“Triterpenes are compounds of natural origin, which have numerously biological activities: anti-cancer properties, anti-inflammatory, anti-oxidative, anti-viral, anti-bacterial and anti-fungal. HIF inhibitor These substances can be isolated from plants, animals or fungi. Nowadays, when neoplasms are main cause of death, triterpenes can become an alternative method for treating cancer because of their cytotoxic properties and chemopreventive activities.”
“This study aimed to characterize the stereoselective
pharmacokinetics of oral eflornithine in 25 patients Selleck AZD6244 with late-stage Trypanosoma brucei gambiense sleeping sickness. A secondary aim was to determine the concentrations of L-and D-eflornithine required in plasma or cerebrospinal fluid (CSF) for an efficient eradication of the T. brucei gambiense parasites. Patients were randomly allocated to receive either 100 (group I, n = 12) or 125 (group II, n = 13) mg/kg of body weight of drug every 6 h for 14 days. The concentrations of L-and D-eflornithine in the plasma and CSF samples
were measured using a stereospecific liquid chromatographic method. Nonlinear mixed-effects modeling was used to characterize the plasma pharmacokinetics. The plasma concentrations of L-eflornithine were on average 52% (95% confidence interval [CI], 51, 54%; n = 321) of the D-enantiomer concentrations. The typical oral clearances of L-and D-eflornithine were 17.4 (95% CI, 15.5, 19.3) and 8.23 (95% CI, 7.36, 9.10) liters/h, respectively. These differences were likely due to stereoselective intestinal absorption. The distributions of eflornithine enantiomers to the CSF were not stereoselective. A correlation was found between the probability of cure and plasma drug exposure, although it was not more pronounced for the L-enantiomer than for that of total eflornithine. This study may explain why oral treatment for late-stage human African trypanosomiasis (HAT) patients with racemic eflornithine has previously failed; the more potent L-enantiomer is present at much lower concentrations in both plasma and CSF than those of the D-enantiomer.
This cross-sectional study investigated the prevalence and clinical characteristics of this neuropathy in patients with Type 2 diabetic mellitus treated at hospitals in Korea. Methods Questionnaires and medical records were used to collect data on 4000 patients with Type 2 diabetes from the diabetes clinics of 40 hospitals throughout Korea. Diabetic peripheral neuropathy was diagnosed based on a review of medical records or using the Michigan Neuropathy Screening Instrument score and monofilament test. selleck Results The prevalence of neuropathy was 33.5% (n = 1338). Multivariate analysis revealed that age, female sex, diabetes duration, lower
glycated haemoglobin, treatment with oral hypoglycaemic agents or insulin, presence of retinopathy, history of cerebrovascular or peripheral arterial disease, presence of hypertension or dyslipidaemia, and history of foot ulcer were independently associated with diabetic peripheral neuropathy. Of the patients with neuropathy, 69.8% were treated for the condition and only 12.6% were aware of their neuropathy. Conclusion There was a high prevalence of peripheral neuropathy in patients with Type 2 diabetes in Korea and those patients were
far more likely to have complications or co-morbidities. The proper management of diabetic peripheral neuropathy deserves attention CCI-779 in vitro from clinicians to ensure better management of diabetes in Korea.”
“Improved fuel consumption and lower emissions are two of the key objectives for future transportation. Hybrid electric vehicles (HEVs), in which two selleck chemicals or more power systems are combined, can meet these objectives through the capture and reuse of regenerated braking energy and through optimized use of the prime mover. However, more complicated power-management strategies are required for such vehicles. This paper explores the potential of applying to advanced power-management strategies for a diesel multiple-unit (DMU) train. These types
of vehicles have multiple diesel engines that are commonly operated in a homogenous manner. This paper analyzes the potential energy savings that may be obtained through the independent operation of the engines. Two widely investigated power-management strategies that have been developed for HEVs have been applied to a typical DMU railroad vehicle. Dynamic programming (DP) strategies have been applied to the results produced by a single-train motion simulator to identify the optimal instant power distribution between the engines. An adaptive rule-based online strategy based on the optimization results from the DP solution is then proposed and realized using a nonlinear programming optimization algorithm. Both strategies indicate acceptable agreement and show a fuel cost reduction of around 7%, in comparison with the evenly split engine operation.”
“Bronchopulmonary dysplasia (BPD) is a complex disorder secondary to gene-environment interactions, and is the commonest chronic lung disease in infancy.
“Neisseria meningitidis is a global cause of meningitis
and septicemia. Immunity to N. meningitidis involves both innate and specific mechanisms with killing by serum bactericidal activity and phagocytic cells. C-reactive protein (CRP) is an acute-phase serum protein that has been shown to help protect the host from several bacterial pathogens, which it recognizes by binding to phosphorylcholine (PC) on their surfaces. Pathogenic Neisseria species can exhibit phase-variable PC modification on type I and 2 pili. We have shown that CRP can bind to piliated meningococci in a MK-0518 mw classical calcium-dependent manner. The binding of CRP to the meningococcus was concentration dependent, of low affinity, and specific for PC. CRP appears to act as an opsonin
for N. meningitidis, as CRP-opsonized bacteria showed increased uptake by human macrophages and neutrophils. Further investigation into the downstream effects of CRP-bound N. meningitidis may lead us to a better understanding of meningococcal infection and this website help direct more effective therapeutic interventions.”
“High-strength cresol isomers were treated with phenol-acclimated granules in batch experiments. The aerobic granules effectively metabolized cresol isomers at concentrations up to 1,500 mg l(-1). The modified Haldane kinetic model, used to assess the kinetic behavior during cresol degradation by granule cells, yielded a high maximum specific growth rate (1.13-1.45 h(-1)) and inhibition constant (617-952 mg l(-1)). The microbial community structure, which was stable under cresol stress, was principally composed of genera Bacillus, Acinetobacter, Corynebacterium, and Nocardioides. Enzyme assay results suggest simultaneous expression of ortho-and meta-cleavage pathways during cresol degradation. Under high cresol concentrations, however, cresol isomers were largely degraded via the meta-cleavage pathway, likely attributable to the activity of
Bacillus. The aerobic granular sludge system is a promising biotechnology for degrading wastewater containing high-strength cresols.”
“This paper reports the synthesis and characterization of ZnO nanoparticles prepared by soft chemical process. Selleckchem SC79 The nanoparticles of ZnO possess wurtzite hexagonal phase and were used for the induction of cell death in malignant human T98G gliomas, KB epitherrnoids and HEK normal non-malignant kidney cells. By applying ZnO nanoparticles, the cells exhibit that the nanoparticles are more efficacious on T98G cancer cells, moderately effective on KB cells and least toxic on normal human HEK cells. The results demonstrated that the treatment with ZnO nanoparticles sensitize T98G cells by increasing both the mitotic (linked to cytogenetic damage) and interphase (apoptosis) death.
no good solution to a dilemma in these medical ethics exists. Our case presents split living liver donation for retransplantation in a mentally disabled girl, with few medical ethics principles at stake.”
“Understanding the disposition kinetics and the pattern of metabolism is critical to optimise the flukicidal activity of triclabendazole (TCBZ) in ruminants. TCBZ is metabolised by both flavin-monooxygenase (FMO) and cytochrome P450 (P450) in the liver. Interference with these metabolic pathways may be useful click here to increase the systemic availabilities of TCBZ metabolites, which may improve the efficacy against Fasciola hepatica. The plasma disposition of TCBZ metabolites was evaluated following TCBZ co-administration with FMO [methimazole (MTZ)] and P450 [piperonyl butoxyde (PB) and ketoconazole (KTZ)] inhibitors in sheep. Twenty (20) healthy Corriedale x Merino weaned female lambs were randomly
allocated into four experimental groups. Animals of each group were treated as follow: Group A, TCBZ alone (5 mg/kg, IV route); Group B, TCBZ (5 mg/kg, IV) + MTZ (3 mg/kg, IV); Group C, TCBZ (5 mg/kg, IV) + PB (30 mg/kg, IV) and Group D, TCBZ (5 mg/kg, IV) + KTZ (10 mg/kg, orally). Blood samples were taken over 240 h post-treatment and analysed by HPLC. TCBZ sulphoxide and sulphone were the main metabolites recovered in plasma. MTZ did not affect TCBZ disposition kinetics. TCBZ sulphoxide Transferase inhibitor Cmax values were significantly increased (P < 0.05) after the TCBZ + PB (62%) and TCBZ + KTZ (37%) treatments compared to those measured in the TCBZ alone treatment. TCBZ sulphoxide plasma AUCs were higher (P < 0.05) in the presence of both PB (99%) and KTZ (41%). Inhibition of TCBZ P450-mediated ML323 in vivo oxidation in the liver accounted for the increased systemic availability of its active metabolite TCBZ sulphoxide. This work contributes to the search
of different strategies to improve the use of this flukicidal drug in ruminants.”
“Introduction: Whooping cough is a re-emerging disease. We describe the investigation of an outbreak of whooping cough and the measures of control adopted.\n\nMethods: The event was reconstructed through a longitudinal study of incidence. In addition to the notified cases, an active search from the list of those who attended summer camps was made through telephone calls. An epidemiological survey was applied to all cases; vaccination history was confirmed with computerised clinical history and the obtaining of samples for analytical confirmation was proposed. The description of the outbreak was made through the epidemic curve, the attack rates, the relative risk and the linear trend by ages and the vaccination coverage.\n\nResults: Of the 30 cases that appeared, 22 (73.3%) were among the members of the summer camps. In these, the attack rate was 21.8%, 26.7% among the children and adolescents increasing linearly with the age. The large majority (86.
Histological observation revealed the cell length of srt7 mutant roots was significantly shorter than that of wild-type roots. Genetic analysis indicated the short root phenotype was controlled CA3 clinical trial by a single recessive nuclear gene. The SRT7 gene was mapped to a 20-kb interval between the markers STS6 and STS7 on chromosome 4 by a map-based cloning method. Sequencing of the six predicted genes in this region found that all of the three allelic mutants contained a 1-bp or 2-bp deletion in the
same gene encoding a putative membrane-bound endo-1,4-beta-glucanase. The SRT7 gene was expressed ubiquitously, with higher levels of transcript accumulation in roots at different developmental stages. However, no difference was found in the SRT7 transcription level between the mutant and wild type. Collectively, these results indicate the endo-1,4-beta-glucanase encoding gene (LOC_Os04g41970) is likely the candidate for SRT7 that functions posttranscriptionally in rice root elongation.”
“The liver is a central organ that controls systemic energy homeostasis and nutrient metabolism. Dietary carbohydrates and lipids, and fatty acids
derived from adipose tissue are delivered to AZD7762 the liver, and utilized for gluconeogenesis, lipogenesis, and ketogenesis, which are tightly regulated by hormonal and neural signals. Hepatic lipogenesis is activated primarily by insulin that is secreted from the pancreas after a high-carbohydrate meal. Sterol regulatory element binding protein-1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) are major transcriptional regulators that induce key lipogenic enzymes to promote lipogenesis in the liver. Sterol regulatory element binding protein-1c
is activated by insulin through complex signaling cascades that control SREBP-1c at both transcriptional and posttranslational levels. Carbohydrate-responsive element-binding protein is activated by glucose independently of insulin. Here, the authors attempt to summarize the current understanding of the molecular mechanism for the transcriptional VX-809 research buy regulation of hepatic lipogenesis, focusing on recent studies that explore the signaling pathways controlling SREBPs and ChREBP.”
“Development of screening programs in patients with high risk of developing esophageal cancer, as well as recent advances in diagnostic endoscopic techniques, have allowed clinicians to improve early detection of esophageal malignant tumors. Surgical resection, although currently considered as the standard of care for patients with early stage esophageal cancer, is sometimes contra-indicated. In this subset of patients, endoscopic resection techniques including endoscopic mucosa! resections (EMR), thermal or non-thermal laser, or cryoablation are amongst the well-recognized modalities safely and efficiently used by gastroenterologists.
A new ‘no-touch’ technique for harvesting grafts may be effective in preventing disruption to the endothelial layer, and subsequent intimal hyperplasia and graft loss. Off-pump surgery and endoscopic
vein harvesting, which are known to reduce surgical morbidity, have been shown to be no worse than on-pump learn more surgery and open vein harvesting, respectively, in terms of vein graft patency. Various gene therapies can prevent intimal hyperplasia in animal models, but human data obtained so far have been disappointing. Placing an external stent around a vein graft may reduce tangential wall stress and subsequent intimal hyperplasia.”
“Xanthomonas oryzae pv. oryzae causes bacterial blight in rice, and this bacterial blight has been widely found in the major rice-growing areas. We constructed a transposon mutagenesis library of X. oryzae pv. oryzae and identified a mutant strain (KXOM9) that is deficient for pigment production and virulence. Furthermore, the KXOM9 mutant was unable to grow in minimal medium lacking aromatic amino acids. Thermal asymmetric
interlaced-PCR and sequence analysis of KXOM9 revealed that the transposon was inserted into the aroC gene, which encodes a chorismate synthase in various bacterial pathogens. In planta growth assays revealed that bacterial growth of the KXOM9 mutant in rice leaves was severely reduced. Genetic complementation of this mutant with a 7.9-kb fragment containing aroC restored virulence, pigmentation, and prototrophy. These results suggest that the aroC gene plays a crucial role in the growth, attenuation of virulence, and
Selleckchem Tozasertib pigment production of X. oryzae pv. oryzae. (C) 2011 Elsevier GmbH. All rights reserved.”
“Optical coherence tomography (OCT) has proven to be an essential imaging modality for ophthalmology and is proving to be very important in neurology. OCT enables high resolution imaging of the retina, both at the optic nerve head and the macula. Macular retinal layer thicknesses provide useful diagnostic information and have been shown to correlate well with measures of disease severity in several diseases. Since manual segmentation of these layers is time consuming and prone to bias, automatic segmentation methods are critical for full utilization of this selleck inhibitor technology. In this work, we build a random forest classifier to segment eight retinal layers in macular cube images acquired by OCT. The random forest classifier learns the boundary pixels between layers, producing an accurate probability map for each boundary, which is then processed to finalize the boundaries. Using this algorithm, we can accurately segment the entire retina contained in the macular cube to an accuracy of at least 4.3 microns for any of the nine boundaries. Experiments were carried out on both healthy and multiple sclerosis subjects, with no difference in the accuracy of our algorithm found between the groups.
The link between intestinal fatty acid-binding
protein and plasma citrulline concentrations in critically ill patients needs to be further evaluated.”
“Eye contact plays an essential role in social interaction. Atypical eye contact is a diagnostic and widely reported feature of autism spectrum disorder (ASD). Here, we determined whether altered unconscious visual processing of eye contact might underlie atypical eye contact in ASD. Using continuous flash suppression (CFS), we found that typically developing (TD) adolescents detected faces with a direct gaze faster than faces with an averted gaze, indicating enhanced unconscious processing of eye contact. Critically, adolescents with ASD did not show different durations of perceptual suppression for faces with direct and averted GSK1120212 order gaze, suggesting that preferential
unconscious processing of eye contact is absent in this group. In contrast, in a non-CFS control experiment, both adolescents with ASD and TD adolescents detected faces with a direct gaze faster than those with an averted gaze. Another CFS experiment confirmed that unconscious processing of non-social stimuli is intact for adolescents with ASD. These results suggest that atypical processing of eye contact in individuals with ASD could be related AG-014699 mouse to a weaker initial, unconscious registration of eye contact. Autism Res2014, 7: 590-597. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.”
“Delayed engraftment remains a major hurdle after HIF-1 pathway cord blood (CB) transplantation. It may be due, at least in part, to low fucosylation of cell surface molecules important for homing to the bone marrow microenvironment. Because fucosylation of specific cell surface ligands is required before effective interaction with selectins expressed by the bone marrow microvasculature can occur,
a simple 30-minute ex vivo incubation of CB hematopoietic progenitor cells with fucosyltransferase-VI and its substrate (GDP-fucose) was performed to increase levels of fucosylation. The physiologic impact of CB hematopoietic progenitor cell hypofucosylation was investigated in vivo in NOD-SCID interleukin (IL)-2R gamma(null) (NSG) mice. By isolating fucosylated and nonfucosylated CD34(+) cells from CB, we showed that only fucosylated CD34(+) cells are responsible for engraftment in NSG mice. In addition, because the proportion of CD34(+) cells that are fucosylated in CB is significantly less than in bone marrow and peripheral blood, we hypothesize that these combined observations might explain, at least in part, the delayed engraftment observed after CB transplantation. Because engraftment appears to be correlated with the fucosylation of CD34(+) cells, we hypothesized that increasing the proportion of CD34(+) cells that are fucosylated would improve CB engraftment.
IL-8 and to a lesser extent IL-6 and IL-1 beta were observed early after inoculation and IL-12 secretion could be measured till late in infection. The ShET2-1,2 mutant, WRSS1 and WRSs3 also colonized the GI tract in a manner similar to Moseley; however, both vaccine candidates developed milder histopathological indices and cytokine responses.
WRSs3-infected animals showed the least pathology. Furthermore, unlike the other strains, WRSs3 was rarely detected in organs outside the gastrointestinal tract. These results support the development of the GB piglet model as a sensitive in vivo oral model for the evaluation of virulence of different Shigella strains which could be applied to other oral vaccine candidates. (C) 2013 Published by Elsevier Ltd.”
“This study focuses on the epidemiology, clinical this website manifestations, risk factors, diagnosis and outcome of all cases of central nervous system (CNS) fungal infections buy S63845 in a tertiary center. Medical records of 18 patients of culture-proven CNS fungal infections were retrospectively reviewed from 2000
to 2007, including 12 isolated from the cerebrospinal fluid (CSF) and seven from tissue biopsy. Patient demographic data included 10 males and eight females. The mean age was 55 years (range: 24-89 years). All but one patient were immunocompromised. Fungal organisms isolated from CSF included: Cryptococcous neoformans (8 patients), Coccidioides immitis (3 patients), and Aspergillus versicolor (1 patient). Histopathology of seven biopsy cases Bioactive Compound Library concentration revealed groups of pigmented golden-brown fungal forms in three cases; three cases showed septate fungi, two of which had melanin in their walls; and one case showed multiple round spherules. These cases on microbiological cultures grew Coccidioides immitis (1 patient), Aspergillus fumigatus (1 patient), Cladophialophora bantiana (2 patients), Fonsecaea monophora (1 patient) and Scedosporium apiospermum (2 patients). Five of the seven fungal organisms isolated from tissue biopsies were
dematiaceous fungi. Twelve patients died after a period of a few weeks to months, two were lost to follow-up, and four are alive with severe neurological sequelae. CNS fungal infections in our cohort were more common in patients post-transplant and with hematologic malignancies. In our series, rare dematiaceous fungi are emerging agents for cerebral mycosis. The outcome of CNS fungal infections is poor despite vigorous antifungal therapy.”
“Following the implementation of the national measles elimination program, the Republic of Korea declared in 2006 that measles had been eliminated. However in 2011, a measles outbreak was reported in Gyeongnam Province in the southeastern part of the country.