1INSERM U781 and Department of Genetics, Hôpital Necker-Enfants Malades, Paris, France. 2Department of Molecular Medicine and Surgery, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden. 3Institut de Génétique et Microbiologie, UMR 8621 CNRS, Université Paris-Sud, Orsay, France. 4Centre National de Génotypage, Evry, France.
Address correspondence to: Agnès Rötig, INSERM U781 and Department of Genetics, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75105 Paris, France. Phone: 33-144-49-51-61; Fax: 33-147-34-85-14; E-mail: roetig@necker.fr.
J Clin Invest. 2007;117(3):765–772. https://doi.org/10.1172/JCI29089.
Oxidative phosphorylation (OXPHOS) deficiency constitutes a clinically and genetically heterogeneous group of inherited diseases. One of these diseases, coenzyme Q10 (CoQ10, ubiquinone) deficiency, is a recently identified entity of particular theoretical and practical importance. CoQ10 transfers reducing equivalents from various dehydrogenases to complex III (ubiquinone cytochrome c reductase) and acts as a transmembrane hydrogen carrier. CoQ10 also plays a critical role in antioxidant defenses (1). Primary CoQ10 deficiency is a rare, but possibly treatable, autosomal recessive condition with 3 major clinical presentations: (a) an encephalomyopathic form, characterized by exercise intolerance, mitochondrial myopathy, myoglobinuria, epilepsy, and ataxia (2–5); (b) a generalized infantile variant with severe encephalopathy and renal disease (6–8); and (c) an ataxic form, dominated by ataxia, seizures, cerebral atrophy, and/or anomalies of the basal ganglia (9, 10). Recurrence of the disease and/or consanguinity of the parents in some reported families suggest an autosomal recessive mode of inheritance. This has been demonstrated by recent reports of OH-benzoate polyprenyltransferase (COQ2) and prenyldiphosphate synthase, subunit 2 (PDSS2) mutation in 2 independent families (11, 12).
Little is known about CoQ10 biosynthesis in humans, but several genes have been identified in the human genome by homology with other organisms, especially the Saccharomyces cerevisiae yeast (Figure 1). In the present study, in an inbred family with CoQ10 deficiency manifesting as a multisystem disease with early-onset deafness, encephaloneuropathy, obesity, livedo reticularis, and valvulopathy, homozygosity mapping allowed the disease to be attributed to a homozygous missense mutation in PDSS1, the enzyme that elongates the prenyl side chain of coenzyme Q. Moreover, direct sequencing of various genes involved in ubiquinone biosynthesis in an unrelated patient with fatal infantile multiorgan disease detected a homozygous single base pair frameshift deletion in COQ2. This study extends our understanding of this newly recognized and possibly treatable cause of OXPHOS deficiency in humans.
CoQ10 biosynthesis pathway. Enzyme and human gene symbols are shown in italics. The yeast gene symbol is indicated when different from the human gene.
Enzymologic studies and quinone quantification. Assessment of individual OXPHOS enzyme activities in cultured skin fibroblasts of patient 1 revealed normal activity of complex II, complex III, and complex IV (Table 1). However, quinone-dependent activities (CII+CIII, glycerol 3 phosphate dehydrogenase [G3PDH]+CIII) were in the range of the lowest control values, and activity ratios (CIV/CII+CIII, CII+CIII/G3PDH+CIII), which optimally detect unbalanced respiratory chain enzyme functions, were markedly altered compared with controls, suggesting quinone deficiency. Muscle mitochondria of patient 1 showed high absolute activity values for all complexes (Table 1) but abnormal activity ratios (CI+CIII/CI, CIII/CI+CIII), also indicating quinone deficiency. The hypothesis of ubiquinone deficiency was further supported by the dramatic effect of decylubiquinone (DQ, an exogenous ubiquinone analog) on succinate oxidation of fibroblasts from patient 1, as addition of DQ during succinate oxidation measurement restored normal activity (8 and 16 nmol/min/mg protein before and after DQ addition, respectively; normal values: 9.8–20.5 nmol/min/mg protein) in the patient's permeabilized fibroblasts (Figure 2A). Consistently, addition of DQ during measurement of succinate–cytochrome c reductase activity restored normal activity of cultured skin fibroblasts (19 and 44 nmol/min/mg protein before and after DQ addition, respectively; normal values: 22–47 nmol/min/mg protein; Figure 2B). Finally, respiratory chain enzyme analysis in the liver of patient 3 revealed normal absolute enzyme activities but increased CIV/CII+CIII and CIV/CI+CIII activity ratios, also suggesting quinone deficiency (Table 1).
Effect of an exogenous quinone analog (DQ, 80 μM) on succinate oxidation (A) and succinate cytochrome c reductase activity of cultured skin fibroblasts from patient 1 (B). Numbers along the traces represent nmol/min/mg protein. Numbers in brackets are normal values. A, absorbance. (C) Elution profiles of lipid extracts from control and patient 3 skin fibroblasts incubated with [3H]mevalonate and treated with acid phosphatase.
Direct evidence of quinone deficiency was finally provided by quantification of CoQ10 in the patients' fibroblasts, as the CoQ10 content of the 3 patients' fibroblasts was markedly decreased compared with normal values (Table 2). Interestingly, a normal CoQ9 level was found in patients 1 and 2. The markedly decreased CoQ10/CoQ9 ratio in patients 1 and 2 (0.3; controls: 13 ± 3) suggested a defective addition of the tenth prenyl to the polyprenyl chain. Fibroblasts from controls and patient 3 were grown in the presence of [3H]mevalonate to estimate the ability of these cells to synthesize CoQ10. Substantial incorporation of [3H]mevalonate into cholesterol, squalene, and dolichol was detected in controls and patient 3, but no [3H]CoQ10 was detected in cultured skin fibroblasts from patient 3 (Figure 2C). In these experiments, all lipid extracts were treated with acid phosphatase to dephosphorylate accumulated intermediates. In patient 3, a peak with a retention time of 18.5 minutes was observed and was identified as decaprenol (Figure 2C). Decaprenyl-pyrophosphate (PP) accumulation reflected a deficiency in COQ2, which conjugates decaprenyl-PP with the benzoquinone ring.
Molecular studies. A genome-wide search for homozygosity was performed in the family of patients 1 and 2 using 400 polymorphic markers. This study identified 6 chromosomal regions of homozygosity on chromosomes 1 (D1S2762–D1S431, 3.9 cM), 7 (D7S2426–D7S2462, 9.4 cM), 10 (D10S1714–D10S593, 9.6 cM), 12 (D12S1608–D12S1685, 5 cM, and D12S1725–D12S77, 11.3 cM), and 13 (D13S280–D13S286, 8.4 cM). The 10p12.2–p12.1 region (Figure 3) encompasses a candidate gene, PDSS1, encoding the prenyldiphosphate synthase, subunit 1, which elongates the prenyl side chain of coenzyme Q in the quinone biosynthesis pathway (1, 13) (Figure 1). A mutation search was therefore undertaken in the family by direct sequencing of the 12 exons of the PDSS1 gene. A homozygous T→G transversion at nucleotide 977 was found in exon 10 (Figure 4A). This transversion resulted in the change of a highly conserved aspartic acid into a glutamic acid (D308E). This aspartic acid is also conserved in eukaryote and prokaryote farnesylpyrophosphate (FPP) synthases and geranylpyrophosphate (GPP) synthases (13–15). Moreover, this aspartic acid lies in the signature pattern of polyprenyl synthase ([LIVMFY]-G-x(2)-[FYL]-Q-[LIVM]-x-D-D-[LIVMFY]-x-[DNG]), an aspartic acid–rich region of the protein that could be involved in the catalytic mechanism and/or binding of the substrates (Figure 4E). Both parents were heterozygous for the T→G transversion (Figure 4B), and unaffected children were either heterozygous or homozygous for the wild-type allele. The T→G transversion created an MnlI restriction site. Exon 10 was amplified, and the PCR product was then digested by the restriction enzyme MnlI. This generated 2 fragments in controls (393 and 180 bp) and 3 fragments in patients (352, 180, and 41 bp; Figure 4D). This mutation was absent from 100 controls of the same ethnic origin.
Pedigree and haplotype analysis of the family of patients 1 and 2. Haplotypes are given (top to bottom) for loci D10S1705, D10S191, D10S1477, D10S1714, D10S211, D10S197, D10S600, D10S593, and D10S1639. The haplotypes in the upper part are from the parents.
Molecular analysis of the PDSS1 gene. Sequence analysis of PDSS1 gene in patient 1 (A), parents (B), and controls (C). (D) MnlI restriction analysis of the T→G mutation at nt 977. MnlI restriction generated 2 fragments of 393 and 180 bp in controls and 3 fragments of 352, 180, and 41 bp in the patient. P, patient; C, controls; MW, molecular weight marker (DNA molecular weight marker VIII; Roche Applied Science). (E) Sequence alignment of the prenyldiphosphate synthase, FPP synthase, and GPP synthase from human and nonhuman sources. The box shows the polyprenyl synthase signature.
Finally, direct sequencing of the genes known to be involved in ubiquinone biosynthesis was systematically performed in patient 3 and identified a homozygous base pair deletion in exon 7 of the OH-benzoate polyprenyltransferase gene (COQ2, c.1198delT, N401fsX415; Figure 5A) resulting in a premature stop codon. Both parents were heterozygous for this single nucleotide deletion (Figure 5B), and the deletion was absent in 100 controls of the same ethnic origin. RT-PCR amplification on fibroblast RNAs showed that the abnormal transcript was still present in patient 3 (Figure 5C). This result suggests that a shortened mutant protein (364 instead of 371 amino acids with 14 C-proximal residues differing from the normal protein) is synthesized in this patient. Unfortunately, no anti-human Coq2 antibody was available to test this hypothesis. Moreover, the global charge of the C-proximal part of the mutant protein was also modified (Figure 5D).
Molecular analysis of the COQ2 gene. Sequence analysis of the COQ2 gene in patient 3 (A) and her parents (B). (C) RT-PCR analysis of COQ2 transcript. (D) Normal and mutant coq2 proteins.
Functional complementation. To confirm the deleterious nature of the D308E PDSS1 genotype, the human wild-type and mutant genes were tested for their ability to complement the OXPHOS defect in the Saccharomyces cerevisiae strain deleted for the COQ1 gene. Wild-type and mutant PDSS1 cDNAs as well as the yeast COQ1 gene were cloned in pYES2.1. The 3 different plasmids were used to transform a yeast Δcoq1-null strain. Growth of the mutant on glycerol-rich medium was restored by the yeast COQ1 gene but not by wild-type or mutant human PDSS1 cDNAs, demonstrating that human prenyldiphosphate synthase does not complement the yeast Δcoq1-null mutation (Figure 6A). The mutation was then introduced into the yeast COQ1 gene by site-directed mutagenesis. The yeast D365E mutant protein (corresponding to the human D308E protein) failed to complement the yeast mutant, whereas the normal protein did, demonstrating that the mutation affects protein function (Figure 6A).
Functional complementation of yeast coq1- and coq2-null mutant. Growth of coq1- and coq2-null mutants on glucose (without amino acids, supplemented with histidine, leucine, and methionine, 20 g/l glucose) or glycerol medium (YPGly, 20 g/l glycerol) was compared. (A) The yeast Δcoq1-null mutant transformed with the wild-type and mutant (D308E) human PDSS1 cDNAs and the wild-type and mutant (D365E) yeast COQ1 genes on the pYES2.1 plasmid. (B) The yeast Δcoq2-null mutant transformed with the wild-type and mutant (m) human COQ2 genes on the pYES2.1 plasmid. The 4 spots for each experiment correspond to successive dilutions of transformed yeasts (1, 0.1, 0.01, and 0.001).
To assess the deleterious nature of the OH-benzoate polyprenyltransferase gene mutation, the yeast Δcoq2-null strain was transformed with either normal or mutant human cDNAs cloned in pYES2.1. The human wild-type cDNA restored growth on glycerol-rich medium, whereas the mutant protein did not, showing that the mutation is indeed the cause of the deficiency (Figure 6B).
This study reports on the identification of deleterious mutations in 2 different genes of the ubiquinone biosynthesis pathway (PDSS1 and COQ2), which caused severe ubiquinone deficiency in 2 unrelated families. In the first consanguineous family, a genome scan analysis identified a homozygous mutation in the PDSS1 gene encoding prenyldiphosphate synthase, one of the key enzymes of the ubiquinone biosynthesis pathway. This enzyme catalyzes elongation of GPP or FPP with several isopentenylpyrophosphate (IPP) groups, in trans configuration, to form the isoprenoid chain (6, 13). The mutation reported here changed a highly conserved aspartic acid into a glutamic acid (D308E). Human wild-type PDSS1 cDNA failed to complement the OXPHOS defect of the Δcoq1-null yeast strain, while the PDSS1 and Coq1p proteins share 35% homology. However, growth of the Δcoq1 yeast strain on a nonfermentable carbon source was restored by the wild-type but not the mutant yeast gene (D365E, corresponding to human D308E). We therefore conclude that the D308E mutation in our patient clearly induced prenyldiphosphate synthase deficiency and a profound quinone biosynthesis defect. In Saccharomyces cerevisiae, Coq1p (hexaprenylsynthase) elongates GPP or FPP (diprenyl biosynthesis intermediaries) to form hexaprenylpyrophosphate. The exact function of the PDSS1 protein in humans is not well known, but it can be hypothesized, by homology with yeast, that the PDSS1 enzyme also elongates geranyl pyrophosphate to form decaprenyl pyrophosphate. However, the normal CoQ9 but very low CoQ10 levels detected in patients 1 and 2 suggest that the D308E PDSS1 mutation only impairs addition of the tenth prenyl to the polyprenyl chain. It is worth noting that quinone-dependent OXPHOS activities were only slightly decreased in patients 1 and 2, despite profound CoQ10 depletion in fibroblasts. It can be hypothesized that the mutant PDSS1 retains a low but significant residual activity, allowing the synthesis of trace amounts of CoQ10 and/or normal amounts of CoQ9 sufficient to maintain a residual respiratory chain function compatible with life.
The mutated amino acid residue (D308) is situated in the second aspartic acid–rich region of the protein, which is common to all prenylsynthases reported to date. This family of proteins also includes FPP synthase and GPP synthase, 2 other enzymes of the ubiquinone synthesis pathway (13–15). Prenylsynthases are also involved in the biosynthesis of terpenoids in plants (16) and carotenoids in fungi (17). These enzymes are also involved in protein farnesylation (18). The aspartic acid–rich prenylsynthase signatures are supposedly involved in binding of the substrate, isopentenyl pyrophosphate, and elongating dimethylallyl pyrophosphate, by forming magnesium salt bridges between the substrate and the catalytic site (13). Site-directed mutagenesis of the second aspartate-rich motif has been performed in FPP synthase from Saccharomyces cerevisiae (19) and Bacillus stearothermophilus (20). These data show that the FPP synthase aspartate residue corresponding to the human PDSS1 residue D308 is essential for catalytic activity. Moreover, the mutagenesis of aspartate to glutamate at position 244 of the rat FPP synthase (D244E), equivalent to the D308E in PDSS1, resulted in a 7-fold reduction in the Vmax value of the enzyme (21). The D308E mutation identified in our patients with ubiquinone deficiency therefore confirms the functional importance of this particular residue for the prenylsynthase activity of the protein.
The OH-benzoate transpolyprenyltransferase (COQ2) gene encodes the enzyme involved in the second step of ubiquinone biosynthesis (13, 22). In a second family with ubiquinone deficiency, a single base pair deletion was identified in the COQ2 gene, resulting in a premature stop codon and modifying the last 21 amino acids of the protein. The normal but not the mutant protein rescued the growth defect of the Δcoq2 yeast strain on a nonfermentable carbon source, therefore demonstrating the deleterious consequences of the mutation. Finally, the abnormal accumulation of decaprenyl-PP, the substrate of OH-benzoate polyprenyltransferase in cultured skin fibroblasts of the patient, also supports the relevance of this mutation in ubiquinone deficiency. The mutated domain of the protein is not well conserved across species, but the mutation modifies the global charge at the C-terminal end of the protein, possibly altering its interactions with other proteins. Several enzymes involved in ubiquinone biosynthesis in yeast have been shown to form a multisubunit complex, as Coq1p, Coq4p, Coq5p, and Coq6p have been shown to form a high-molecular-weight complex (23, 24). It is not yet known whether Coq2p is also involved in this complex in yeast and whether a similar complex exists in humans. Nevertheless, the deleterious effect of this human mutant protein in yeast suggests that various interactions between the proteins of the 2 species are still retained despite the absence of sequence homology between human and yeast Coq2p at the C-terminal ends of the proteins.
Primary ubiquinone deficiency is a rare cause of mitochondrial disorders, and the genetic bases of these disorders have rarely been identified, as COQ2 or PDSS2 mutations have only been reported twice in patients with encephalomyopathy and kidney involvement (11, 12). In this article, we report what we believe to be the first molecular/functional characterization of PDSS1 and COQ2 mutations and demonstrate that both mutations are disease causing.
It is noteworthy that optic atrophy, deafness, obesity, pancytopenia, and cardiac disease have not been previously reported in primary ubiquinone deficiency. While optic atrophy, deafness, and pancytopenia are occasionally reported in respiratory chain deficiency, it remains unclear whether obesity and valvulopathy are directly related to ubiquinone deficiency. Similarly, early and severe forms of ubiquinone deficiency, fatal in the early neonatal period, have seldom been reported (7). Why profound ubiquinone deficiency in cultured fibroblasts was associated with either neonatal death or long survival also remains unexplained (patients 1 and 2 were 22 and 14 years old, respectively). The clinical heterogeneity of ubiquinone deficiency is suggestive of a genetic heterogeneity that could be related to the large number of enzymes and corresponding genes involved in ubiquinone biosynthesis. It is hoped that identification of disease-causing genes in other families will help to elucidate the clinical variability of these rare conditions.
Patients. We obtained informed consent from parents and all probands and siblings before collecting blood for DNA extraction or performing tissue biopsies. Patient 1, a boy, was born to first-cousin healthy Moroccan parents. He had 3 unaffected brothers and 1 affected sister. He was normal at birth (weight, 2.7 kg; height, 47 cm; head circumference, 35 cm). Deafness was detected at 1 year of age, and he developed bulimia, obesity, livedo reticularis, and optic atrophy at 3 years. Valvulopathy characterized by mild aortic and mitral regurgitation with moderate pulmonary artery hypertension was detected at the age of 15. At the time of publication, he was 22 years old, with mild mental retardation, and, unlike his healthy siblings, he presented overweight (weight, 73 kg + 1.5 SD; height, 1.58 m – 2 SD) and macrocephaly (head circumference, 57 cm + 1.5 SD). He also has a peripheral neuropathy with absent deep tendon reflexes. Mildly elevated plasma lactate (2.1 mmol/l; N, 1.0–1.55) and lactate/pyruvate molar ratios (16; N, 6–14) were observed, and muscle biopsy showed mitochondrial aggregates.
Patient 2, his sister, was normal at birth (weight, 2.9 kg; height, 46 cm; head circumference, 34 cm). She also developed deafness in her second year and valvulopathy at the age of 9 years. At the time of publication, she was 14 years old and presented obesity (weight, 75 kg + 4 SD; height, 133 cm), macrocephaly (head circumference, 57 cm + 3 SD), optic atrophy, peripheral neuropathy, and mental retardation similar to that of her brother. She also has livedo reticularis and mildly elevated plasma lactate levels (3.2 nmol/l; N, 1.0–1.55) and lactate/pyruvate ratios (21; N, 6–14).
Patient 3, a girl, was born to healthy parents of French origin. Both parents were from the same geographical region and shared the same patronymic, but they were not aware of any consanguinity. She presented neurologic distress at birth. Liver failure and nephrotic syndrome were diagnosed at 2 days of age. At 6 days, she developed anemia, pancytopenia, insulin-dependent diabetes, cytolysis, and seizures and presented hyperlactatemia (22.7 mmol/l) and high lactate/pyruvate molar ratios. She died at 12 days of age from multiorgan failure. Her older brother experienced collapse with hyperglycemia (15 mmol/l) and hyperlactatemia shortly after birth (16 mmol/l). He also had severe anemia, liver failure, and renal insufficiency and died at the age of 1 day.
Enzyme studies. Polarographic tests and/or spectrophotometric OXPHOS enzyme assays were carried out on skeletal muscle mitochondria, muscle homogenate, liver homogenate, cultured skin fibroblasts, or circulating lymphocytes, as previously described (25).
Genotyping. Fluorescent microsatellite markers of the Généthon database were used (26). The purified dye-labeled fragments were separated according to size on Amersham Biosciences MegaBACE 1000 96-capillary sequencers.
Analysis of CoQ10 content and biosynthesis in skin fibroblasts. All solvents (Merck) were HPLC grade. Quinones were extracted from freeze-thawed fibroblasts (106 cells in 1 ml of water) according to the method of Folch et al. (27), with 3 ml of chloroform/methanol (2:1) and 5 pmol of CoQ6 (Sigma-Aldrich) as internal standard. After shaking and centrifugation (2,000 g; 5 minutes), the organic layer was evaporated under a nitrogen stream at 60°C and resuspended in 100 μl of methanol. CoQ10 was quantified by liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry using a triple quadruple tandem mass spectrometer (API3000; Applied Biosystems) coupled with a liquid chromatographic system (HP 1100 series; Agilent Technologies). Lipid extracts (20 μl) were injected into an Uptisphere ODB column (33 × 2 mm, 3 μm; Interchim) and separated by a linear gradient from 40% solvent A (methanol/water, 9:1) to 90% solvent B (chloroform/methanol, 1:1) at 500 μl/min for 2 minutes for a total run time of 5 minutes (column oven maintained at 35°C). Multiple-reaction monitoring transitions were 863.9–197.2 and 591.5–197.2 for CoQ10 and CoQ6, respectively. CoQ10 content was expressed with reference to the protein content of the cell extracts. Cells were labeled with [3H]mevalonate, and extraction of lipids and HPLC analyses were performed as previously described (6). Since decaprenyl-PP cannot be separated by reverse-phase HPLC, both phases of lipid extracts (petroleum ether and methanol) were combined, dried, and subjected to treatment with wheat germ acid phosphatase (28). Decaprenol was identified on the HPLC chromatogram by a reference sample and mass spectrometry.
Mutation screening. The exons and exon-intron boundaries of the human prenyldiphosphate synthase (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) genes were PCR amplified using specific intronic primers (Table 3). Amplification products were directly sequenced using the PRISM Ready Reaction Sequencing Kit (Applied Biosystems) on an automatic sequencer (Applied Biosystems).
Complementation of a yeast coq1- and coq2-null mutant. The COQ1 gene was PCR amplified using oligonucleotide primers COQ1-1 and COQ1-1419 and cloned in a pYES2.1 plasmid according to the manufacturer's recommendations (Invitrogen). The D365E mutation was introduced into the wild-type yeast COQ1 gene cloned in pYES2.1 using the QuikChange XL site-directed mutagenesis kit (Stratagene) and COQ1-mutF and COQ1-mutR primers (Table 3; the mutation is shown in parentheses). Human wild-type and mutant PDSS1 cDNAs were RT-PCR amplified from control and patient fibroblast RNA using PDSS1-F and PDSS1-R primers (Table 3) and cloned in a pYES2.1 plasmid. Human wild-type COQ2 cDNA previously cloned in a pBV134.nuc vector (gift from I. Climent, Biovitrum, Stockholm, Sweden) was PCR amplified using COQ2-1 and COQ2-1114 primers and cloned in pYES2.1 plasmid. The c.1198delT, N401fsX415 mutation was introduced into the wild-type COQ2 cDNA using the site-specific mutagenesis kit (Stratagene) and COQ2-mutF and COQ2-mutR primers (Table 3; the deletion is shown in parentheses).
The yeast Δcoq1 and Δcoq2 strains (his–, ura–, leu–, met–) were transformed according to ref. 29, and the resulting clones were grown on yeast base plates without amino acids supplemented with histidine, leucine, and methioine and replicated on a glycerol-rich medium for 3–4 days at 30°C.
We thank Isabel Climent (Biovitrum) for providing us with human COQ2 cDNA. This research was supported in part by the Association Française contre les Myopathies and by the Fondation Jérôme Lejeune.
Nonstandard abbreviations used:COQ2, OH-benzoate polyprenyltransferase; CoQ10, coenzyme Q10; DQ, decylubiquinone; FPP, farnesylpyrophosphate; G3PDH, glycerol 3 phosphate dehydrogenase; GPP, geranylpyrophosphate; OXPHOS, oxidative phosphorylation; PDSS1, prenyldiphosphate synthase, subunit 1; PP, pyrophosphate.
See the related article at Mutations in coenzyme Q10 biosynthetic genes.
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text:
Honduras president-elect hopes for small majority in Congress
Xiomara Castro hopes her left-wing party can muster the congressional votes to rewrite the country's constitution.
Honduras President-elect Xiomara Castro will have to negotiate with other parties to pass legislation in a split Congress [Elmer Martinez/AP Photo]
Published On 1 Dec 20211 Dec 2021
Honduran President-elect Xiomara Castro, the first woman to lead the Central American nation, is awaiting results from tight legislative races to see if her left-wing party would gain control of Congress, a day after her main rival conceded defeat.
With the right-wing National Party's 12-year hold on power set to end when Castro is inaugurated in January, attention on Wednesday shifted to the fate of the 128-member Congress.
The congressional balance of power is in the air, but preliminary results appeared to point to the possibility of a simple majority for Castro's party and its allies – if the trend of the current vote tally holds.
That would ease the passage of some of Castro's legislative priorities, but her pledge to convoke an assembly to rewrite the Honduran constitution could still be blocked since that would require a two-thirds majority.
Denis Gomez, a former electoral council member, estimated that Castro's Free Party would win 51 seats, while its main ally, the party of Vice President-elect Salvador Nasralla, would get 14, giving the governing coalition a one-member majority.
But Gomez stressed that this projected makeup of the unicameral legislature could still change if the trend in the count shifts.
It is unclear when the final vote count will be announced.
"If that majority doesn't hold, they would have to negotiate," he said, most likely with the centre-right Liberal Party, which after the National Party, is projected to form the third-largest bloc in the next Congress.
Political analyst Raul Pineda was less cautious about Castro's influence over incoming lawmakers. He said her party, working with the vice president's party, will "have a simple majority to reform or repeal laws".
But Castro and her allies would need to peel off nearly 20 more votes, most likely from the Liberal Party, to reach a two-thirds majority for constitutional reforms, Pineda added.
The same super-majority also would be needed to elect new members of the Supreme Court and a new attorney general.
In addition to political wrangling in Congress, Castro will face other major challenges as she steps into the role of president in the Central American country.
Unemployment is above 10 percent, northern Honduras was devastated by two major hurricanes last year, and street gangs have dragged down the economy with extortion rackets and violence, driving migration to the United States.
US Secretary of State Anthony Blinken congratulated Castro on her victory on Tuesday night and said he looked forward to working with her to "strengthen democratic institutions, promote inclusive economic growth and fight corruption".
The Honduran people exercised their power to vote in a free and fair election. We congratulate them and President Elect @XiomaraCastroZ and look forward to working together to strengthen democratic institutions, promote inclusive economic growth, and fight corruption.
— Secretary Antony Blinken (@SecBlinken) December 1, 2021
Castro's government could present challenges, but also opportunities for the administration of US President Joe Biden, which had sought to keep her predecessor at arm's length over concerns about corruption and ties to drug gangs.
Many Castro supporters remember the US government's initial sluggishness in calling the 2009 overthrow of Castro's husband Manuel Zelaya from the presidency a coup, and then proceeding to work closely with the National Party presidents who followed.
From the US perspective, Washington remembers how Castro and Zelaya cosied up to then-Venezuela President Hugo Chavez.
But analysts have said common ground between Castro and the US government exists in at least three areas: immigration, drug trafficking and corruption. And with tense relations prevailing between Washington and the leaders of El Salvador and Guatemala, the US government could use a productive relationship with Honduras.
Despite opponents' efforts to paint Castro as a communist, experts expected her to govern as a centrist with a desire to lift up Honduras's poor while attracting foreign investment.
In a speech in June, Castro pledged to propose a plan to the Biden administration to "combat and address the true causes of migration".
Castro describes Hondurans' emigration in terms of flight to escape inequality, corruption, poverty and violence. That is not too different from how senior officials in the Biden administration have framed the issue, and where they have said they want to focus US aid.
But Castro also puts some of the blame on the US government.
"I believe the Biden administration has an enormous opportunity to address the issue of migration," Castro said in the June speech. "First, recognising that they have part of the responsibility for what happens in our country," she added, noting the 2009 coup.
Castro has hammered the administration of outgoing President Juan Orlando Hernandez over corruption.
It was Hernandez's administration that let the Organization of American States' anti-corruption mission in Honduras expire in 2020 after its work had touched some of the National Party's lawmakers for alleged misuse of public funds.
She has said she is interested in having an international anti-corruption mission return to Honduras. That, combined with a strong, independent attorney general, could begin to tackle one of the country's most profound problems.
US federal prosecutors have put corruption under the microscope in drug trafficking cases that have reached high-ranking Honduran politicians. The most notable was the conviction of Hernandez's brother, a former federal lawmaker, on drug trafficking charges that earned him a life sentence in the US.
Source: News Agencies

redpajama_set_name: RedPajamaCommonCrawl


text:
The Strengths Revolution
Positive Risk-Taking webinar
Strengths Resources
Working with Strengths (2014)
Risk Decision-Making (2013)
The Art of Co-ordinating Care (2009)
Working with Risk (2007)
Steve Morgan
Welcome to 'The Strengths Revolution' with Steve Morgan… helping inquisitive people like you to maximize your strengths, so you become more of who you really are. Whether you are looking to develop your own potential, or to get the most out of your team or organisation, tune into my weekly podcast show where I will share ideas and simple strategies to help you identify strengths, tap into your personal resources, and take calculated risks. In 2017 this has become a location for my brief YouTube risk & strengths training videos, primarily developed for my 'Positive Risk-Taking' Membership Site.
Subscribe to this blog to get an email notification each time something new is posted. You can also contact me directly at stevemorgan57@hotmail.com
BRIEF BIOGRAPHICAL DETAILS
Following an initial career as a qualified Town Planner Steve Morgan has briefly worked as an Occupational Therapist on an acute in-patient unit in the mid-1980's, before taking up roles in community mental health and assertive outreach in inner-city London services from 1987 to 1997. He spent 7 years working in the Sainsbury Centre for Mental health training section (initially on a part-time secondment), before leaving in October 2001 to establish his own practice development consultancy: Practice Based Evidence.
Gained an M.A. in 'Practice Development in Mental Health' in 1998, with the National Centre for Work Based Learning at Middlesex University. Published textbooks training manuals and articles from 1993 onwards (see lists below), and established his website (www.practicebasedevidence.com) from February 2004. This podcast show, The Strengths Revolution, commenced in April 2014.
Steve project managed the fieldwork for the National Audit Office Crisis Teams Study (2007), published findings from seven Practice Based Evidence assertive outreach team practice development projects (2008), and is currently a member of the Royal College of Psychiatrists Accreditation Committee for Home Treatment Teams. He joined Neuro Health Case Management Services in February 2013, and Westcountry Case Management in December 2015 currently working with a small caseload of people experiencing acquired brain injury and/or severe physical trauma.
PUBLICATIONS C.V.
1. "Community Mental Health : Practical Approaches to Long-Term Problems" (1993). Cheltenham, Nelson Thornes (formerly Chapman & Hall, London).
2. "Helping Relationships in Mental Health" (1996). Cheltenham, Nelson Thornes (formerly Chapman & Hall, London).
3. "Assertive Outreach: A Strengths Approach to Policy and Practice" (2004). Edinburgh, Churchill Livingstone. (Written with Peter Ryan).
4. "The Art of Co-ordinating Care: a handbook of best practice for everyone in care and support" (2009). Brighton, OLM-Pavilion. (Written with Andrew & Roberta Wetherell).
5. "Risk Decision-Making: Working with risk and implementing positive risk-taking" (2013). [Manual & CD-Rom] Brighton, Pavilion Publishing & Media.
6. "Working with Strengths: Putting Personalisation and Recovery into Practice" (due April 2014). Brighton, Pavilion Publishing & Media.
Contributory Chapters
1. Ch. 12 – "The Assessment and Management of Risk" pp265-290. In: Charlie Brooker and Julie Repper (eds) "Serious Mental Health Problems in the Community" (1998). London, Balliere Tindall.
2. Ch. 26 – "Caring for the patient with substance misuse" pp961-989. In: M. Walsh (ed.) "Watson's Clinical Nursing and Related Sciences" 6th edn. (2002). London, Balliere Tindall. (Written with Tara O'Neill).
3. Ch. 22 – "Case management and assertive outreach" pp261-273. In: B. Hannigan and M. Coffey (eds) "The Handbook of Community Mental Health Nursing" (2003). London, Routledge.
4. Ch. 8 – "Assessing and managing risk" pp208-240. In: I. Norman and I. Ryrie (eds) "The Art and Science of Mental Health Nursing: A Textbook of Principles and Practice" (2004). Maidenhead, Open University Press. (Written with Andrew Wetherell).
5. Ch. 11 – "Working with risk" pp231-259. In: I. Norman and I. Ryrie (eds) "The Art and Science of Mental Health Nursing: A Textbook of Principles and Practice". 2nd Edition (2009). Maidenhead, Open University Press. (Written with Andrew Wetherell).
6. Ch. 14 – "Funky Mental Health" pp238-250. In: C. Williams, M. Firn, S. Wharne and R. Macpherson (eds.) "Assertive Outreach in Mental Healthcare: Current Perspectives" (2011). Chichester, Wiley-Blackwell. (Written with Sue Jugon).
1. "Down Your Street : models of extended community support services for people with mental health problems" (1998). Sainsbury Centre for Mental Health, London. (Joint authorship with Lesley Warner, Richard Ford, Sandra Bagnall, Catriona McDaid, Sonia Mawhinney).
2. "Active Outreach: An independent service user evaluation of a model of assertive outreach practice" (2001). Sainsbury Centre for Mental Health, London. (Written with Roberta Graley-Wetherell).
3. "How can 'Positive Risk-Taking' help build Dementia-Friendly Communities?" (11th November 2014). A 'Viewpoint' publication by the Joseph Rowntree Foundation. Written with Toby Williamson, Mental Health Foundation).
4. "Reflective Exercise 2: Magic Moments and Positive Risk-Taking" (April 2016). Pp 25-26 in: Andrews, N. (Ed.) 'Magic Moments: Inspire, Motivate, Support!' Swansea: Swansea University.
1. "You What, John ? " (1992). Case Management Quarterly, R.D.P., London.
2. "Strengths Case Management : A Focus on Ability" (1995). Ergoterapeuten (Norwegian Journal of Occupational Therapy), 38(8):24-8.
3. "Managing Risk and Promoting Safety in the Community" (1996). Editorial feature for 'CMHT Manager', Issue 7 : Aug/Sept. Mental Health Foundation, London.
4. "Different pathways to employment" (1997). Offprint 39, The Open University School of Health and Social Welfare, Course K257 : Mental Health and Distress : Perspectives and Practice. (With Jill Reynolds).
5. "Assessing Personal Strengths" (1997). Argentina Journal of Occupational Therapy – Materia Prima, 1(2) : 5-6.
6. "Assertive Outreach : Implications for the development of the model in the United Kingdom." (1999 – Hemming, M., Morgan, S. and O'Halloran, P.) Journal of Mental Health, 8(2) : 141-147.
7. "Balancing care and control : risk management and compulsory community treatment." (1999, with Mark Hemming). Mental Health & Learning Disabilities Care, 3(1) : 19-21.
8. "Assertive Outreach : Risk-making or Risk-taking?" (2000).Openmind, 101: 16-17.
9. "Assertive Outreach : the importance of being focused." (2000). Care Plan, 7(1) : 12-16.
10. "Scaling Paper Mountains" (2001). Openmind, 107: 20-21.
11. "They asked what I needed" (2002 with Roberta Graley-Wetherell). Mental Health Today, March pp 25-27.
12. "Practice based evidence" (2002 with David Juriansz). Openmind, 114: 12-13.
13. "Uncovering creative capability" (2002 with David Juriansz). Mental Health Today, July pp 25-28.
14. "Strengths-based practice" (2004). Openmind, 126: 16-17.
15. "Positive risk-taking: an idea whose time has come" (2004). Health Care Risk Report, 10(10): 18-19.
16. "Reshaping the risk agenda" (2005). Openmind, 135: 19.
17. "CPA: process or event?" (2007). Openmind, 143: 19-21.
18. "Visions of risk" (2007). Openmind, 146: 7-8.
19. "Learning Curve: Working with Risk" (2007). Mental Health Today, September pp36-37.
20. "One foot in the door" (2008 with Kirt Hunte). Mental Health Today, March pp32-35.
21. "Whose crisis?" (2008 with Kirt Hunte). Openmind, 150: 18-19.
22. "Strengths Assertive Outreach: A Review of Seven Practice Development Programmes" (2008). Mental Health Review Journal, 13(2): 40-46.
23. "Personalisation revisited" (2009). Openmind, 159: 10-11.
24. "Positive risk-taking: a basis for good risk decision-making" (2010). Health Care Risk Report, 16(4): 20-21.
25. "Making good risk decisions in mental health and social care" (2010). Health Care Risk Report, 16(5): 16-17.
26. "Opportunities and risks of the personalisation agenda" (2010). Nursing Management, 17(2): 20-22.
27. "A Risky Business" (2010). Learning Disability Today, August/September pp18-20.
28. "Reflective practice in staff training" (2012). Open Mind, 172: 20-21.
29. "Positive risk-taking: from rhetoric to reality" (2016 with Nick Andrews). Journal of Mental Health Training, Education and Practice, 11(2): 122-132.
1. "Access to Employment, Volunteering, Education, Training and other Satisfying Activities." Module 4, Section 8; Course K257 : Mental Health and Distress : Perspectives and Practice. The Open University School of Health Welfare and Community Education (1994/5 for 1997).
2. "Assessing & Managing Risk" (1998) Sainsbury Centre for Mental Health, and Pavilion, Brighton. 2-part training package for practitioners and managers of Community Mental Health Teams: Part 1 – 2 day Trainers Manual; Part 2 – Practitioner Handbook.
3. "Implementing Assertive Outreach" (1999). Unpublished paper, with Deborah Davidson and Mark Hemming.
4. Ch. 6 – "Individual Care Planning in the UK". In : Thurstine Bassett (ed.) "Looking to the Future : key issues in contemporary mental health services" (2000). Pavilion, Brighton (for Mental Health Foundation – Certificate in Community Mental Health Care course). Written with Su Akbar-Khan.
5. Ch. 7 – "Risk and Safety". In : Thurstine Bassett (ed.) "Looking to the Future : key issues in contemporary mental health services" (2000). Pavilion, Brighton (for Mental Health Foundation – Certificate in Community Mental Health Care course).
6. "Clinical Risk Management: A Clinical Tool and Practitioner Manual." (2000). Sainsbury Centre for Mental Health, London.
7. "Learning and Development Resources". On-line training materials jointly developed with Caroline Godleman to support the implementation of the Department of Health risk framework: Independence, choice and risk: a Guide to best practice in supported decision making' (2007).
8. "Working with Risk." (2007). A Trainers Manual & Practitioners Manual. OLM-Pavilion, Brighton.
1. "Are Crisis Resolution & Home Treatment Services seeing the patients they are supposed to see?" A report of fieldwork visits for the National Audit Office (2007). Written with Jess Hudson, Kirt Hunte and Roberta Wetherell.
2. "Making the CPA work for you: service users & carers and the Care Programme Approach" (National Leaflet). Produced for the Department of Health in collaboration with ARW Training Consultancy (March 2008).
3. "Making the CPA work for you: service users & carers and the Care Programme Approach" (National Booklet). Produced for the Department of Health in collaboration with ARW Training Consultancy. (March 2008).
4. "Making the CPA work for you: service users & carers and the Care Programme Approach" (National DVD). Produced for the Department of Health in collaboration with ARW Training Consultancy (March 2008).
5. "Risk Enablement" Frontline Briefing for Research in Practice for Adults. Rosie McNamara and Steve Morgan (February 2016).
1. "Finance and Mental Health" (1996). Derek Heptinstall, for The Matthew Trust.
2. "Keys to Engagement" (1998). London, Sainsbury Centre for Mental Health.
3. Onyett, S. (2003) Teamworking in mental health. London, Palgrave.
2 thoughts on "About"
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I upgraded to get more space. Did not get a confirmation email, it went through. I downloaded videos and they do not show up in the video gallery I created. When uploaded photos, stops at 99% and locks up.
I have asked someone from the PS.com team to contact you.
Can you send me your account ID (email address for this account) to rcoencas@adobe.com and I'll have someone on our team take a look at your account status and get back to you ASAP.


text:
Food Science internships enable students to get experience related to their field of study, usually while receiving academic credit and wages.
Interns often return to campus with a better understanding of how their course work relates to the real world and a clearer picture of their career goals. They also see how an industry or organization in which they're interested actually works, and they return to school more motivated to excel.
Along with providing valuable experience, internships can be a direct pathway to that first job. Employers increasingly use internships to develop a pool of qualified applicants. In fact, according to the College Placement Council, 35 percent of 624 companies recently surveyed said interns were their most important source of new full-time employees.
A typical internships usually lasts about three months during the summer, although some food companies offer co-op or work-study programs that extend into the fall or spring semester. Typically, an intern will be assigned to a project and expected to prepare and present a written report at the end of the summer.
Among the many companies that have recently offered internships to Food Science students are:
Campbell Soup Company
Mondelez Internatioanal
JM Smucker Company
Agropur Dairy Cooperative
Saputo Cheese
Students interested in applying for internships and co-op programs should contact Chris Andrus (cma18@psu.edu, 814-863-8667).
College of Ag Sciences Internship Website
More Content from Undergraduate Programs
Undergraduate Programs Overview
Career Placement
Potential Career Paths and Salaries
Potential Career Paths and Salaries Overview
Our Graduates at Work
Why Major in Food Science?
Nittany Lion Careers Recruit Food Science Students
College of Ag Sciences: All Majors and Minors


text:
Q: ejabberd disconnects on bad XML message Ejabberd disconnects with the client if it experience a bad xml from the client.
Is it possible to configure ejabberd not to disconnect in such cases?

A: I didn't found any related option in https://docs.ejabberd.im/admin/configuration/ and I guess that won't exist.

A: You can use a reconnecting mechanism so that the application can reconnect automatically whenever the internet connection lost or an error occurs (depending on your requirement).
As an example this is the reconnection manager for Smack
Some similar questions where you might find a solution

*

*How to keep a XMPP connection stable on Android with (a)smack?

*ReconnectionManager in asmack

A: It is standard behaviour for a server to disconnect on malformed XML, because there is no good way to recover from such mistake. For example, if you forget to close a tag, then, your whole stream is broken, because all stanzas are suddenly at the wrong level.
There is no reason for a client to send invalid XMPP stanza. This should be considered a bug to fix in the client.
If you accept user input causing the stanza to get malformed, you need to proerly encode / escape the content.

redpajama_set_name: RedPajamaStackExchange


Midway University's Nursing Program is highly regarded and respected. Our nurses are sought out in the healthcare industry, many times before they even graduate. This is due to our knowledgeable faculty, high quality facilities and dedication to developing strong clinical skills in each student.
Students who successfully complete the ADN program are eligible to take the National Council Licensure Examination (NCLEX-RN). Successful completion of this exam allows the graduate to practice as a Registered Nurse (RN).
The undergraduate nursing program curriculum has a dual focus. Classroom theory emphasizes the technical and theoretical aspects of nursing. Concentrated, supervised clinical laboratory experiences allows students to practice skills at several health care agencies in Central Kentucky. The ADN program prepares students to become registered nurses and qualifies them for seamless transition into our RN to BSN program.
Admission to Midway's Associate and Bachelor of Science in Nursing programs is selective. Students hoping to begin nursing careers with a science degree should be aware that a certain educational background or preparation is important to assure admission to the nursing program.
If students are interested in earning their BSN, Midway also offers a 4-year pre-licensure Bachelor of Science in Nursing program.
How can an Associate in Nursing degree work for you? The Bureau of Labor Statistics estimates a 16 percent growth in Registered Nurse jobs between 2014 and 2024, an increase that is much faster than average.
Our ADN graduates qualify for most any RN position. Examples of positions of recent graduates include staff nurses on Medical-Surgical Units, Cardiovascular, Neuro, Orthopedics, Labor and Delivery, Newborn Nursery, Pre and Post-Partum Units, Pediatrics, a variety of specialty Intensive Care Units including Neonatal, and Skilled Nursing Homes.
Students who successfully complete the Associate Degree in Nursing and pass the NCLEX-RN may have a seamless transition into the RN-BSN program.
Students must first apply and be admitted into Midway University. We offer a simple online application process. Create your account, submit all materials and track your application status conveniently online. Paper application forms are available for download if needed. Admissions Counselors are available to assist you with the application process and answer any questions you may have about Midway University and our programs. Give them a call at 1-800-952-4122 or email admissions@midway.edu.
Complete your nursing application during the spring semester for possible admission to the fall semester.
What are the admissions requirements for the ADN program?
Admission to Midway's Associate and Bachelor of Science in Nursing programs is selective. Students hoping to begin nursing careers with a science degree should be aware that a certain educational background or preparation is important to assure admission to the nursing program. Please review our full list of nursing admission criteria prior to applying.
The nursing programs are accredited by the Accreditation Commission for Education in Nursing, Inc., 3343 Peachtree Road NE, Suite 850, Atlanta, GA 30326, 404.75-5000, Fax 404.975.5020 (www.acenursing.org). The Associate Degree Nursing Program also has full approval by the Kentucky Board of Nursing (KBN), 212 Whittington Parkway, Suite 300, Louisville, KY 40222, 502.429.3300, Fax 502.429.3311 (www.kbn.ky.gov).
Visit Financial Aid for more details.
Midway University works hard to provide quality degree programs at an affordable price for our students. Our online and evening undergraduate and graduate programs' tuition is based on the number of credit hours taken each module. You can review our current credit hour tuition rates and fees online.
Make sure you get the whole picture before making your decision. First, complete your FAFSA so you can see what financial aid you are eligible to receive and complete your application. Once you are admitted to Midway University, you can meet with our Financial Aid Office to discuss all the eligible aid (federal, state and institutional) that you have access to. This is the only way to figure out the true cost and if you will have any out-of-pocket expenses to cover. We also have specific resource information for military students.
A full estimated cost list for the ADN program is available for download.
Can I transfer credits from another school if I am accepted into this program?
Midway University accepts transfer credits from regionally accredited institutions that are 100-level or higher with a grade of "C" or better. At the time of admission, our Admissions Counselors will provide an unofficial evaluation of your transfer credit. An official evaluation will be completed by the Registrar's Office after acceptance.
What support services are available for online and evening students?
Midway's Nursing Faculty are always available via email, phone, face-to-face meetings or Zoom web meetings to assist our students. Our job is to work with you throughout the program to ensure your successful understanding of the concepts and curriculum components.
Midway University's Student Success Center provides both Academic Support and Career Services resources for all Midway students. Academic Support includes one-on-one tutoring, small group tutoring and virtual (or online) tutoring. Workshops are held throughout the year to support student learning.
Career Services resources are available to students, alumni and others within our community to help them gain relevant and practical career readiness training through education and experiential learning within internships, job shadowing, career counseling and strategic corporate partnerships.
Don't see your question here? Our admissions staff would be happy to discuss our degree programs with you and answer your questions. Get the conversation started by calling us at 800.952.4122 or by email at admissions@midway.edu.
You will earn your ADN degree in 64 credit hours. Once students are officially admitted to the nursing program and begin their nursing courses, day students will complete the program in 2 years and evening students will complete in just 18 months.
Nursing courses must be taken in the following sequence: NSG 115, NSG 120, NSG 210, NSG 225 and NSG 230, and a grade of C must be earned in each before progressing to the next level.
Students will be required to take nationally-normed assessments, Assessment Technologies Institute (ATI), throughout the curriculum. The focus of the ATI assessment and remediation programs is to supplement course work and enhances preparation to pass the NCLEX-RN.


text:
Phycosecis hilli is een keversoort uit de familie Phycosecidae. De wetenschappelijke naam van de soort is voor het eerst geldig gepubliceerd in 1921 door Lea.

Phycosecidae

redpajama_set_name: RedPajamaWikipedia


text:
Ната́лья Серге́евна Земцо́ва (род. 7 декабря 1987 года, Омск) — российская актриса.

Биография
Земцова родилась 7 декабря 1987 года в Омске. Обучалась в омской языковой гимназии № 115. В московский вуз после школы поступить ей не удалось, в результате она год проучилась при омском ТЮЗе, затем поступила на дневное отделение в СПбГАТИ, на курс А. М. Зеланда.
Вела программу «Креативный класс» на канале СТС.

Снялась для обложки мужского журнала MAXIM за май 2013 года.

Личная жизнь

В августе 2014 года Земцова родила сына, которого назвали Иваном. Отцом ребёнка стал музыкант Сергей Кристовский, в июне 2016 года он и Земцова официально узаконили свои отношения. Кристовский старше своей супруги на 16 лет, и для заключения этого брака ему пришлось развестись с женой, оставив четверых детей.

30 апреля 2022 года в интервью журналу PeopleTalk Наталья сообщила о разводе с Сергеем Кристовским.

Фильмография
  — Счастливы Вместе — Наташа Белоногова  — Голоса — дочь Подрезова (15 серия)
 2010 — Любовь на районе — Катя, двоюродная сестра Ани  — Мы — одна семья (Моя безумная семья) — эпизодическая роль
 2011 — Опережая выстрел — Вика
 2011 — Интернат — Юля
 —2016 — Восьмидесятые — Инга Бородина
  — Кухня — Наталья, подруга Луи
 2013 — Пропавшие без вести — лейтенант Ольга Николаевна Кузнецова (в 14 эпизодах)
 2013 — Морские дьяволы. Смерч. Судьбы — Ирина (в эпизоде «Фильм № 11. Один в поле воин (Кот)»)
  — Невидимки — сотрудница в офисе 2014 — Последняя минута 2 — незнакомка (в эпизоде «На крючке»)
 2014 — Смешанные чувства — официантка Жанна 2014 — Что творят мужчины! 2
 2016 — Выйти замуж любой ценой — Ирина 2018 — Другие — Марина —2020 — Эпидемия — Марина Кубасова 2020 — Метод 2 — подставная девушка  — Потерянные — Катя Завьялова («Тема»), блогер  — Чикатило — Валентина, жертва Чикатило в Новошахтинске  ― Второе зрение 2 ― Маргарита Черешнева, капитан следственного управления 2022 — Многоэтажка — Маша  — Химера — Светлана ТВ-передачи
 «Хорошие шутки» на СТС — участница
 «Креативный класс» на СТС — ведущая вместе с Александром Пушным
 «Побей Пушного» — участница

 Примечания

 Ссылки
 Профиль на сайте rusactors.ru
 Профиль на сайте ''ruskino.ru

Выпускники Российского государственного института сценических искусств
Персоналии:Театр Армена Джигарханяна


Master Degree in "Legal and Economic Framework of Business in the EU"
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The Visual Arts exhibition of our International Baccalaureate (IB) students was officially open on Monday, April 8th. Many students, parents and teachers from BSS enjoyed the beautiful pieces of art, displayed at the exhibition.
The IB Diploma Programme Visual Arts course encourages students to challenge their own creative and cultural expectations and boundaries.
The 2-year course is designed for students who want to go on to study visual arts in higher education. It consists of theoretical practice, art-making practice and curatorial practice. A part of the internal assessment is the exhibition. Students submit a selection of artworks as a portfolio. They should explain how these works are connected.
"Your work is phenomenal. If you have a talent, you need to celebrate it and we, as a school we should celebrate it and encourage you. It gives you the opportunity to think creatively and outside of the classroom", said Mr. Matthew Osborn, Headmaster of BSS, at the official opening of the Visual Arts Exhibition.


Montréal's public bike system – the first launched in North America – features over 5000 self-service bikes available 24hr across the city at 450-plus stations, from April to November. Montréal researched similar bike programmes in other cities, including Paris and Barcelona, to emerge with the well-oiled, wonderfully accessible Bixi (w bixi.com; the name comes from "bike" plus "taxi"). Renting a bike is simple: at a Bixi stand (which are all solar-powered, and liberally scattered across the city), swipe your credit card and ride off. A 24hr access pass is $5; during that period, you can borrow bikes as often as you like, and the first 30min is free. Beyond that, you pay additional charges. A 72hr pass is $12. Also on offer are 30-day ($30) and one-year ($85) subscriptions.


My scalp has been itchy and flaky since grade school. For years I used various types of dandruff shampoos, with the most effective being tar-based formulas. In the past decade science has caught up with my condition and now I use over-the-counter Nizoral Shampoo which contains an anti-fungal chemical that kills off the fungus that my scalp is allergic to (this fungus is natural and grows on everyone's heads - but some of us are allergic to it).
I also use 2 other treatments on my hair: A salicylic acid/alcohol 'wash' (Scalpicin), and a hydrocortisone/alcohol 'wash' (Maximum Strength Scalpicin) - one or the other, once a week or so. These are a more powerful method of sterilizing the scalp and calming down the inflammation which causes the terrible itchiness. As a result, my condition is well managed these days.
© Performance Solutions 2019. Vancouver, Canada.


text:
Sergeant Arthur Stuart Meade 1501
© IWM (HU 125503)
Use this image under non-commercial licence.
The media for this item are free to reuse for non-commercial purposes under the IWM Non Commercial Licence and can be downloaded or embedded with the code we offer here. By downloading or embedding any media, you agree to the terms and conditions of the IWM Non Commercial Licence, including your use of the attribution statement specified by IWM. For this item, that is: © IWM (HU 125503)
Purchase & License
    Sergeant Arthur Stuart Meade 1501 © IWM (HU 125503)
[url=https://www.iwm.org.uk/collections/item/object/205385682][img]https://media.iwm.org.uk/ciim5/427/214/mid_000000.jpg?action=e&cat=Photographs[/img][/url] [url=https://www.iwm.org.uk/collections/item/object/205385682]Sergeant Arthur Stuart Meade 1501. © IWM (HU 125503)[/url] [url=https://www.iwm.org.uk/corporate/privacy-copyright]IWM Non Commercial License[/url]
Sergeant Arthur Stuart Meade 1501. Unit: 3rd Reinforcements, 1st Battalion, Australian Imperial Force. Death: 05 June 1915 Gallipoli
Son of James Arthur and Frances Meade, of Young, New South Wales. Native of Major's Creek.
Half length portrait
First World War (production), First World War (content)
HU 125503
BOND OF SACRIFICE - FIRST WORLD WAR PORTRAITS COLLECTION
Object associations
Associated people and organisations
Meade, Arthur Stuart
Sergeant Henry Alexander Charles Mead
Collection: MEADS ARTHUR
© IWM (E(AUS) 2078)
How did people share their cultures and traditions during the First World War?
© IWM (Art.IWM PST 2734)
First World War Recruitment Posters
© IWM (CH 19)
How has war in the air changed over time?


When I saw the quote above, I immediately knew that it was something I needed to share with you. As we are asked to do a newborn session, we know how important this time is and how quickly time passes. We are so blessed to be part of the newest chapters in their lives. The truth is our little one's never stay little. After the days have passed of swaddling our little bundles of joy, the only memory [or evidence for their wedding day] we have left are photos.
Maurena and Dan, congrats again on your little guy! Mackenzie, we are so excited that you get to be a BIG sister! Gavin we are so grateful to have been a part of your welcoming to the world. We know your big sister will take great care of you.


The World Anti-Doping Agency suspects that Russia has corrupted officials from the International Biathlon Union in order to protect its athletes and its interests, « Le Monde » reveals.
How many banknotes can you fit in a diplomatic suitcase ? The debate is still open when Grigori Rodchenkov, director of Moscow's anti-doping centre, enters the room. Alexander Tikhonov, vice-president of the International biathlon union (IBU), argues that it can hold between 200 000 and 300 000 dollars (between 160 000 and 240 000 euros). Alexander Kravtsov, head of the russian mission for the Sotchi Olympic Winter Games, thinks that as much as 400 000 dollars can fit inside.
The question is important : they have to know with certainty the amount of money that was given to the Norwegian Anders Besseberg, president of the IBU, to ensure his support for russian interests in biathlon.
The scene is thought to have taken place in the summer of 2013. It was recounted to the investigators of the World Anti-Doping Agency (WADA) by Grigori Rodchenkov himself, now a whistleblower living in the United States. According to a classified investigation by WADA, that Le Monde has read, Russia has been infiltrating the IBU for many years, a similar pattern with what happened in athletics.
Investigators collected the testimonies from an anonymous informant and from Grigori Rodchenkov on the relationships between russian sport officials and those of the IBU : its president, Anders Besseberg, and his secretary-general, Nicole Resch. On April 11th, WADA announced that Austrian and Norwegian police had carried out, on the 10th, simultaneous searches at the headquarters of the IBU in Salzburg and at the home of Mr. Besseberg. The IBU said in a press release that Nicole Resch had asked to take leave from her position during this investigation that could call into question Russia's return to grace on the international sports scene.
The 16 page report, signed by Günter Younger, head of the investigation department of WADA, are devastating for Mr. Besseberg, the first and only president of the IBU since 1993. They are another confirmation that an important part of the Russian biathlon team was, for the last years, benefiting from PEDs and being protected from prosecution.


text:
EU Parliament Takes First Step Towards a Fair and Interoperable Market
By Christoph Schmon
Update: On December 15, the European Parliament overwhelmingly approved important key changes to the EU Commission's Digital Markets Act Proposal, including a prohibition on dark patterns and ambitious rules to help ensure interoperability of messaging and social media network services. The Parliament also added more options for users to switch default settings and apps. We applaud the commitment to helping foster the emergence of new platforms and services. The Parliament's text will be up for interinstitutional negotiations with the Council of Europe and the EU Commission in the coming months. Both institutions support important key features of modern anti-monopoly and fairness rules. However, the Commission's proposal and the Council's position do not explicitly support interoperability rules. EFF will work to ensure the final text gives users more control over their internet experience.
The EU's Proposal for a Digital Market Act (DMA) is an attempt to create a fairer and more competitive market for online platforms in the EU. It sets out a standard for very large platforms, which act as gatekeepers between business users and end users. As gatekeepers "have substantial control over the access to, and are entrenched in digital markets," the DMA sets out a list of dos and don'ts with which platforms will have to comply. There was a lot to like in the initial proposal: we agreed with the DMA's premise that gatekeepers are international in nature, applauded the "self-executing" nature of many obligations, and supported the use of effective penalties to ensure compliance. Several anti-monopoly provisions showed ambition to end the corporate concentration and revitalize competition, such as the ban on mixing data ((Art 5(a)), the ban on forced single sign-ons (Art 5(e)), the ban on cross-tying (Art 5(f)), and the ban on lock-ins (Art 6(e).
End-Users Perspective: EFF Pushes for Interoperability
However, we didn't like that the DMA proposals missed the mark from the end-user perspective, in particular the lack of interoperability obligations for platforms. The Commission met us half-way by introducing a real-time data portability mandate into the DMA, but it failed to go the full distance. Would it lead to a measurable behavioral change of Facebook if frustrated users could only benefit from data portability if they continued being signed up to Facebook's terms of service? We doubt it.
The EU Parliament's Lead Committee Calls for Interconnection and Functional Interaction
In today's vote, the Internal Market Committee (IMCO) of the EU Parliament overwhelmingly agreed to preserve most of the proposed anti-monopoly rules and agreed on key changes of the Commission's Proposal. We'll analyze them in more details in the coming weeks, but some elements are striking. One is that the Committee opts for an extremely high threshold before platforms will be hit by the rules (market capitalization of at least €80bn) which means that only a few, mainly U.S based, firms would legally be presumed to act as gatekeepers and hold an entrenched and durable position in the internal market. Members of Parliament also agreed on incremental improvements on the ban of mixing data, added clarification on the limits of targeted ads, including substantial protection of minors, and introduced an ambitious dark patterns prohibition in the DMA's anti-circumvention provision. It also added a prohibition on new acquisitions as a possible punishment for systematic non-compliance with the anti-monopoly rules.
On interoperability, Members of Parliament followed the strong recommendation by EFF and other civil society groups to not settle for the low-hanging fruits of data portability and interoperability in ancillary services. Focusing on the elephant in the room - namely, messaging services and social networks - the DMA's lead committee proposes key provisions that would allow any providers of "equivalent core platform services" to interconnect with the gatekeeper's number independent interpersonal communication services (like messaging apps) or social network services upon their request and free of charge. To avoid discrimination, interconnection must be provided under objectively the same conditions and quality that are available or used by the gatekeeper, its subsidiaries, or its partners. The objective is a functional interaction with these services while guaranteeing a high level of security and data protection.
Competitive Compatibility
Another positive feature is the DMA's anti-circumvention provision, which follows EFF's suggestions by stating that gatekeeper should abstain from any behavior that discourages interoperability by using "technical protection measures, discriminatory terms of service, subjecting application programming interfaces to copyright or providing misleading information." (Article 6(a)).
Interoperability Caveats
The interoperability obligations for gatekeeper come with caveats and question marks. The implementation of the interconnection rules for messaging services is subject to the requirements of the Electronic Communications Code, while those for social networks depend on yet-to-be-defined specifications and standards. The phrasing, too, leaves room for interpretation. For example, the relationship between the obligation to provide interconnection and how to provide it ("same conditions available or used") is unclear and could lead to restrictions in practice. On the other hand, the Preamble of the DMA is makes the legislative intent crystal-clear. It explains that "the lack of interconnection features can affect users' choice and ability to switch due to the incapacity for end user to reconstruct social connections and networks provided by the gatekeeper." Providers of alternative core platform services should thus be allowed to interconnect. For number-dependent intercommunication services, this means that third-party providers can request interconnection for features "such as text, video, voice and picture;" for social networking services, this means interconnection on basic features "such as posts, likes, and comments".
Next Steps: Vote and Negotiations
It's now the job of the EU lawmakers to put this objective into a clear and enforceable language. The text approved in committee will be submitted for vote to the full House in an upcoming plenary session and the Council of the EU, whose position is much less ambitious, must also agree on the text for it to become law. EFF will continue pushing for rules that can end corporate concentration.
Deeplinks Blog by Christoph Schmon | December 14, 2021
Digital Services Act: EU Parliament's Key Committee Rejects a Filternet But Concerns Remain
Fix What is Broken vs Break What Works: Oscillating Between Policy ChoicesThe European Union's Digital Services Act (DSA) is a big deal. It's the most significant reform of Europe's internet platform legislation in twenty years and the EU Commission has proposed multiple new rules to address the challenges brought...
Deeplinks Blog by Christoph Schmon | November 10, 2021
European Parliament's Plans Of A Digital Services Act Threaten Internet Freedoms
The EU's Digital Services Act is a chance to preserve what works and to fix what is broken. EFF and other civil society groups have advocated for new rules that protect fundamental rights online, while formulating a bold vision to address today's most pressing challenges. However, while the initial...
Deeplinks Blog by Cory Doctorow | October 27, 2021
Europe's Digital Services Act: On a Collision Course With Human Rights
Last year, the EU introduced the Digital Services Act (DSA), an ambitious and thoughtful project to rein in the power of Big Tech and give European internet users more control over their digital lives. It was an exciting moment, as the world's largest trading bloc seemed poised to end a...
Deeplinks Blog by Karen Gullo | October 21, 2021
The European Parliament's regulations and policy-making decisions on technology and the internet have unique influence across the globe. With great influence comes great responsibility. We believe the European Parliament (EP) has a duty to set an example with the Digital Services Act (DSA), the first major overhaul of European...
Deeplinks Blog by Karen Gullo | September 28, 2021
Cross Border Police Surveillance Treaty Must Have Clear, Enforceable Privacy Safeguards, Not a Patchwork of Weak Provisions
This is the fourth post in a series about recommendations EFF, European Digital Rights, the Samuelson-Glushko Canadian Internet Policy & Public Interest Clinic, and other civil society organizations have submitted to the Parliamentary Assembly of the Council of Europe (PACE), which is currently reviewing the Second Additional Protocol to...
Deeplinks Blog by Christoph Schmon, Karen Gullo | September 28, 2021
EFF, Access Now, and Partners to European Parliament: Free Speech, Privacy and Other Fundamental Rights Should Not be Up for Negotiation in the Digital Services Act
The European Committee on Legal Affairs adopted the proposals discussed here on Sept. 30 by a vote of 15+/9-. The proposals now go to the Committee on the Internal Market and Consumer Protection (IMCO), which will develop a position with a vote scheduled for November 8. European Union (EU) civil...
Deeplinks Blog by Cory Doctorow | June 11, 2021
The GDPR, Privacy and Monopoly
In Privacy Without Monopoly: Data Protection and Interoperability, we took a thorough look at the privacy implications of various kinds of interoperability. We examined the potential privacy risks of interoperability mandates, such as those contemplated by 2020's ACCESS Act (USA), the Digital Services Act and Digital Markets Act (EU),...
Deeplinks Blog by Christoph Schmon | March 18, 2021
Twitter, Trump, and Tough Decisions: EU Freedom of Expression and the Digital Services Act
This blog post was co-written by Dr. Aleksandra Kuczerawy (Senior Fellow and Researcher at KU Leuven) and inspired by her publication at Verfassungsblog.Suspension of Trump's Social Media Accounts: Controversial, but not unprecedentedThe suspension of the social media accounts of former U.S. President Donald Trump by Twitter, Facebook, Instagram,...
Deeplinks Blog by Christoph Schmon, Cory Doctorow | December 26, 2020
EU and the Digital Services Act: 2020 Year in Review
While 2019 saw the EU ramming through a disastrous Internet copyright rule that continues to reverberate through legal and policy circles, 2020 was a very different story as the EU introduced the Digital Services Act (DSA), the most significant reform of Europe's platform legislation the EU has...
Deeplinks Blog by Cory Doctorow, Christoph Schmon | December 15, 2020
The EU's Digital Markets Act: There Is A Lot To Like, but Room for Improvement
After lengthy consultations and many rumors and leaks, the European Commission has released its public draft of the Digital Markets Act (DMA), which, along with the Digital Services Act (DSA,) represents the first major overhaul of EU Internet legislation in the 21st Century. Like the DSA, the DMA...


EDINA, MN — Looking for a new home, and want to get a better understanding of what's available near you? Need some assistance finding the perfect place for you and your loved ones? You've come to the right place! To help simplify your search, we've compiled an up-to-date batch of five new listings nearby.
Below, you'll find the five latest homes to go up for sale in the Edina area — such as one in the Minneapolis area with 2 beds and 1 bath for $199,900, and another with 5 beds and 2 baths for $849,900.
That's not all! Keep scrolling for more listings. And there are even more homes for you to check out in our real-estate section for the Edina area.


Tying Brooke Bliss' feet down, we now have easy access to those ticklish tootsies. Her giggling starts out nice and light as LB traces his fingers over her soles, as she even comments that it's like a pedicure. This light tickling doesn't last long, however. When he brings the oil out, combining it with our tickling gloves. Poor little Brooke is struggling like crazy trying to get her feet away from that evil tickling tool. It tickles her so much that her innocent language shifts over to some swears. It looks like we've found she kryptonite for tickling!


text:
/*  Symbol Table Classes */

/*  Copyright (c) 1994 Stanford University

    All rights reserved.

    This software is provided under the terms described in
    the "suif_copyright.h" include file. */

#include <suif_copyright.h>

#ifndef SYMTAB_H
#define SYMTAB_H

#pragma interface

RCS_HEADER(symtab_h,
    "$Id: symtab.h,v 1.2 1999/08/25 03:29:17 brm Exp $")

class in_stream;
class out_stream;
class base_symtab_list;
class file_set_entry;
class tree_block;
struct replacements;

enum symtab_kinds {
    SYMTAB_GLOBAL,
    SYMTAB_FILE,
    SYMTAB_PROC,
    SYMTAB_BLOCK
};

/* These functions affect how base_symtab::write() writes out the duplicate
 * symbol names. */

extern void enable_automatic_renaming(void);
extern void disable_automatic_renaming(void);

/*
 *  The ID numbers used for sym_nodes and type_nodes are divided into
 *  three ranges.  To make it easier to read an ID number, this function
 *  prints it as a single character to identify the range ("g" = global,
 *  "f" = file, "p" = procedure) combined with the offset of the number
 *  within that range.
 */

extern void print_id_number(FILE *fp, unsigned id);

/*
 *  A symtab contains lists of symbols and types that may be used within the
 *  scope associated with the symtab.  The base_symtab class is abstract and
 *  contains variables and methods shared by all of the other symbol tables.
 *  The symtabs form a strict hierarchy starting with the global symtab,
 *  followed by one symtab per file, followed by symtabs for the individual
 *  procedures and blocks.  Each symtab has a name and all of the children of
 *  a particular symtab should have unique names.  Symtabs are automatically
 *  removed and destroyed along with the corresponding "scopes", e.g.
 *  deleting a tree_block also deletes its block_symtab.
 */

class base_symtab : public suif_object {
    friend class sym_node;
    friend class type_node;
    friend class var_def;

private:
    void chain_name_helper();

protected:
    sym_node_list *syms;		/* list of symbols */
    var_def_list *defs;			/* variable definitions */
    type_node_list *typs;		/* list of types */
    base_symtab *par;			/* parent symtab */
    base_symtab_list *childs;		/* list of child symtabs */
    char *nm;				/* name of this symtab */
    unsigned next_sym_id;		/* next unused symbol ID number */
    unsigned next_type_id;		/* next unused type ID number */
    unsigned var_counter;		/* for creating unique var_syms */
    string_index *sym_name_index;	/* for fast lookups by name */
    ptr_index *def_index;		/* for fast lookups by var_sym */
    ptr_index *sym_id_index;		/* for fast lookups by id # */
    ptr_index *type_id_index;		/* for fast lookups by id # */

    void print_contents(FILE *fp, int depth);

    void add_contents_to_replacements(replacements *r);
    virtual base_symtab *new_peer(char *n) = 0;
					/* create a new symtab of the same
					   sub-class as this one */

    void register_name_change(sym_node *the_sym, char *new_name);
    void register_sym_id_change(sym_node *the_sym, unsigned new_id);
    void register_type_id_change(type_node *the_type, unsigned new_id);
    void add_name_entry(sym_node *the_sym, char *new_name);
    void remove_name_entry(sym_node *the_sym, char *old_name);
    void register_def_sym_change(var_def *the_def, var_sym *new_var);

    void set_sym_extern(sym_node *the_sym, boolean new_value)
      { the_sym->set_extern(new_value); }
    void set_sym_id(sym_node *the_sym, unsigned new_id)
      { the_sym->set_sym_id(new_id); }

    void remove_def_internal(var_def *d, boolean in_destructor);

public:
    base_symtab(char *n);		/* the symtab name */
    virtual ~base_symtab();

    object_kinds object_kind()		{ return SYMTAB_OBJ; }

    virtual symtab_kinds kind() = 0;

    boolean is_global()			{ return ((kind() == SYMTAB_GLOBAL) ||
						  (kind() == SYMTAB_FILE)); }
    boolean is_file()			{ return (kind() == SYMTAB_FILE); }
    boolean is_block()			{ return ((kind() == SYMTAB_BLOCK) ||
						  (kind() == SYMTAB_PROC)); }
    boolean is_proc()			{ return kind() == SYMTAB_PROC; }

    base_symtab *parent()		{ return par; }
    sym_node_list *symbols()		{ return syms; }
    var_def_list *var_defs()		{ return defs; }
    base_symtab_list *children()	{ return childs; }
    type_node_list *types()		{ return typs; }
    char *name()			{ return nm; }
    char *chain_name();			/* writes to static buffer! */

    void set_name(char *n);
    void rename_duplicates();		/* give unique names to everything */

    base_symtab *lookup_child(char *name);
    var_def *lookup_var_def(var_sym *v);
    type_node *lookup_type(type_node *t, boolean up=TRUE);
    sym_node *lookup_sym(char *name, sym_kinds k, boolean up=TRUE);
    var_sym *lookup_var(char *name, boolean up=TRUE)
	{ return (var_sym *)lookup_sym(name, SYM_VAR, up); }

    boolean is_visible(type_node *the_type)
	{ return is_ancestor(the_type->parent()); }
    boolean is_visible(sym_node *the_sym)
	{ return is_ancestor(the_sym->parent()); }

    sym_node *lookup_sym_id(unsigned i);
    type_node *lookup_type_id(unsigned i);

    var_sym *new_var(type_node *t, char *n);
    var_sym *new_unique_var(type_node *t, char *base = NULL);
    var_def *define_var(var_sym *v, int a);

    boolean is_ancestor(base_symtab *s);

    /* add a type and its component types if they do not already exist in this
       or a parent symtab; deletes type_nodes that are replaced */
    type_node *install_type(type_node *t);

    /* attempt to move a type so that it is visible in this scope */
    boolean make_type_visible(type_node *t, boolean check = FALSE);

    void resolve_exposed_refs(replacements *r);
    base_symtab *clone_helper(replacements *r, boolean no_copy = FALSE);

    void add_child(base_symtab *c);	/* sets c->parent */
    virtual void add_sym(sym_node *s);	/* sets s->table */
    void add_type(type_node *t);	/* sets t->table */
    void add_def(var_def *d);		/* sets d->table */

    void remove_child(base_symtab *c);	/* doesn't delete c */
    void remove_sym(sym_node *s);	/* doesn't delete s */
    void remove_type(type_node *t);	/* doesn't delete t */
    void remove_def(var_def *d);	/* doesn't delete d */

    virtual void print(FILE *fp=stdout, int depth=0) = 0;
    virtual void write(out_stream *os);
    virtual void read(in_stream *is);
};

DECLARE_DLIST_CLASS(base_symtab_list, base_symtab*);

/*
 *  The global_symtab at the root of the symbol table hierarchy is used to
 *  hold symbols and types shared across files (i.e. those with external
 *  linkage).  This class is also reused as the base class for file_symtabs.
 *  Since only global and file symtabs may contain procedure symbols, this
 *  class includes methods to create new proc_syms and to lookup existing
 *  ones.  The number_globals function is automatically called just before
 *  writing the symtab to assign ID numbers to new symbol and type nodes.
 */

class global_symtab : public base_symtab {
    friend class file_set;

protected:
    virtual base_symtab *new_peer(char *n) { return new global_symtab(n); }

public:
    global_symtab(char *n);		/* name (usually "global") */

    symtab_kinds kind()			{ return SYMTAB_GLOBAL; }

    proc_sym *new_proc(func_type *r, src_lang_type src, char *n);
    proc_sym *lookup_proc(char *s, boolean up=TRUE)
	{ return (proc_sym *)lookup_sym(s, SYM_PROC, up); }

    void predefine_types();		/* create common types */
    void number_globals();

    void add_sym(sym_node *s);
    void print(FILE *fp=stdout, int depth=0);
    void write(out_stream *os);
};

/*
 *  A file symtab is associated with a particular file_set_entry to hold
 *  symbols and types declared in the scope of the file (e.g. it contains
 *  the global variables declared with "static" linkage).  This class is
 *  identical to the global_symtab class except for the file_set_entry
 *  pointer.
 */

class file_symtab : public global_symtab {
    friend class suif_linker;

private:
    file_set_entry *fset;		/* corresponding file_set_entry */

    void set_fse(file_set_entry *new_fse) { fset = new_fse; }

protected:
    virtual base_symtab *new_peer(char *n)
      { return new file_symtab(n, fse()); }

public:
    file_symtab(char *n,		/* name (usually the input filename) */
		file_set_entry *fse);	/* corresponding file_set_entry */

    symtab_kinds kind()			{ return SYMTAB_FILE; }
    file_set_entry *fse()		{ return fset; }

    void print(FILE *fp=stdout, int depth=0);
};

/*
 *  The block_symtab class is used for nested block symbol tables and as the
 *  base class for procedure symbol tables.  Each one is associated with a
 *  particular tree_block (or tree_proc).  The "new_unique_child" method can
 *  be used to create a new child block symtab with a unique name.  Since
 *  label symbols may only be entered in symtabs within procedures, this
 *  class provides methods to create new labels and lookup existing ones.
 */

class block_symtab : public base_symtab {
    friend class tree_block;
    friend class tree_proc;

private:
    unsigned label_counter;		/* for creating unique label_syms */

protected:
    tree_block *blk;			/* corresponding block */

    void set_block(tree_block *b)	{ blk = b; }
    void number_locals(unsigned *next_sym_idp, unsigned *next_type_idp);

    virtual base_symtab *new_peer(char *n) { return new block_symtab(n); }

public:
    block_symtab(char *n);		/* block name */

    symtab_kinds kind()			{ return SYMTAB_BLOCK; }
    tree_block *block()			{ return blk; }

    block_symtab *new_unique_child(char *base = NULL);

    label_sym *new_label(char *n);
    label_sym *new_unique_label(char *base = NULL);

    label_sym *lookup_label(char *s, boolean up=TRUE)
	{ return (label_sym *)lookup_sym(s, SYM_LABEL, up); }

    void find_exposed_refs(base_symtab *dst_scope, replacements *r);
    block_symtab *clone_helper(replacements *r, boolean no_copy = FALSE);

    void add_sym(sym_node *s);
    void print(FILE *fp=stdout, int depth=0);
    void write(out_stream *os);
    void read(in_stream *is);
};

/*
 *  A proc_symtab is used as the top-level symbol table for a procedure.
 *  This class is basically the same as the block_symtab class with a few
 *  extensions.  The proc_symtab also contains the list of parameters for
 *  the procedure.  This is an ordered list of pointers to var_syms in the
 *  symtab; the flags for these var_syms must also be set to indicate that
 *  they are parameters.  All of the instructions within the procedure are
 *  assigned unique numbers, and the proc_symtab keeps track of the next
 *  instruction number to be used.  (The "tree_proc::number_instrs" function
 *  is used to assign these instruction numbers.)  Finally, the "number_locals"
 *  function is called automatically just before writing the symtab to
 *  assign ID numbers to the symbols and types in this symtab and all of its
 *  descendants.
 */

class proc_symtab : public block_symtab {
    friend class block_symtab;
    friend class tree_proc;

private:
    sym_node_list *prms;		/* parameter list (in order) */
    unsigned next_inum;			/* next unused instruction number */

protected:
    virtual base_symtab *new_peer(char *n) { return new proc_symtab(n); }

public:
    proc_symtab(char *n);		/* name (usually the procedure name) */
    ~proc_symtab();

    symtab_kinds kind()			{ return SYMTAB_PROC; }
    sym_node_list *params()		{ return prms; }

    unsigned instr_num()		{ return next_inum; }
    unsigned next_instr_num()		{ return next_inum++; }

    void number_locals();

    proc_symtab *clone_helper(replacements *r, boolean no_copy = FALSE);

    void print(FILE *fp=stdout, int depth=0);
    void write(out_stream *os);
    void read(in_stream *is);
};

#endif /* SYMTAB_H */

redpajama_set_name: RedPajamaGithub


TOKYO, Sept 4 (Reuters) - The dollar firmed on Tuesday as investors bid up safe haven assets amid tensions around global trade and strains in emerging market currencies, while the Australian dollar pared losses after Australia's central bank kept interest rates on hold.
On Saturday, Trump said there was no need to keep Canada in the North American Free Trade Agreement and warned Congress not to meddle with the talks to revamp NAFTA or he would terminate the trilateral trade pact.
"It seems that the dollar, helped by rising interest rates, and the yen, the typical haven currencies, are supported by the confusion in the rest of the world," said Masafumi Yamamoto, chief currency strategist at Mizuho Securities.
As of 0403 GMT, the dollar index against a basket of six currencies was 0.1 percent higher at 95.231, nearing its highest level since Aug. 27.
The dollar's status as the world's reserve currency tends to attract safe haven bids in times of market turmoil and political tensions.
The Australian dollar rose 0.06 percent to $0.7216, as the Reserve Bank of Australia decided on Tuesday to keep its cash rate at 1.5 percent, as widely expected.
The Aussie retraced earlier losses of about 0.3 percent shortly after the rate decision, moving off a 20-month low of $0.71655 touched during the previous session.
The euro was down 0.15 percent at $1.1601. Data released on Monday showed euro zone manufacturing growth slowing to a near two-year low in August as optimism dwindled due to the lingering threat of a global trade war.
Similar surveys in Asia showed the region's key exporting nations coming under strain from the escalating global trade frictions.
Also on Monday, Argentine President Mauricio Macri announced new taxes on exports and steep cuts to government spending in what he termed "emergency" measures to balance next year's budget, underlining the turbulence gripping some emerging markets.
Kumiko Ishikawa, senior analyst at Sony Financial Holdings, said anxiety has come to the fore as a result of multiple issues, including the China-U.S. trade war and uncertainty about how the NAFTA talks will play out.
"If things are like that, there are no moves to sell the yen to take risk," she said, adding that the yen rather than emerging market currencies will be bought "when the mood worsens".


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