limitam o uso na terapia clínica, como agranulocitose, cardiotoxicidade e hepatotoxicidade.
oxidativo, tornando-a um fármaco mais seguro aos pacientes.
Palavras-chave: esquizofrenia, clozapina, nanossistemas, vias de estresse oxidativo.
clozapine-loaded chitosan-coated or polyethyleneglycol-coated nanocapsules (25 mg/Kg i.p.).
Keywords: schizophrenia, clozapine, nanosystems, oxidative stress pathways.
comentários gerais sobre os resultados mostrados nos manuscritos deste trabalho. No item PERSPECTIVAS, estão expostos os possíveis estudos para dar continuidade a este trabalho.
Os RL induzem o estresse oxidativo e danos em todos os tipos de moléculas biológicas e podem estar envolvidos na patologia da esquizofrenia (HALLIWELL, 2006; DIETRICH- MUSZALKA & OLAS, 2009; HALLIWELL, 2012a; 2012b). O cérebro e o SNC são propensos ao estresse oxidativo, pois estão insuficientemente equipados com sistemas de defesa antioxidante para prevenir o dano oxidativo imposto pelas doenças neurodegenerativas (HALLIWELL, 2006). Em pacientes esquizofrênicos ocorre a desregulação do metabolismo de ERO e ERN, tal processo pode ser verificado através das análises das atividades anormais das enzimas antioxidantes, além de outros biomarcadores de estresse oxidativo como a peroxidação lipídica em plasma, glóbulos vermelhos, plaquetas e/ou líquido cefalorraquidiano (REDDY & YAO, 1996; YAO et al., 1998; DIETRICH-MUSZALKA, OLAS & RABE-JABLONSKA, 2005). Tais achados tem sido associados com discinesia tardia, sintomas negativos e sinais neurológicos (LI et al., 2006). Estudos sugerem que o excesso de formação de ERO pode desempenhar um papel crucial na etiologia da esquizofrenia. A disfunção da membrana celular causada pela peroxidação lipídica pode ser secundária a uma patologia mediada por RL e pode contribuir para a sintomatologia e complicações do tratamento. Estudos realizados por meio da avaliação da atividade da enzima antioxidante SOD em plaquetas evidenciaram a indução de estresse oxidativo em pacientes esquizofrênicos, sugerindo que a supressão da atividade da SOD em pacientes com esquizofrenia está associada com maior geração de ERO e da peroxidação lipídica (DIETRICH-MUSZALKA, OLAS & RABE-JABLONSKA, 2005).
Dentre os sistemas carreadores de fármacos, os sistemas nanoparticulados, compostos que apresentam diâmetro entre 10 e 1000 nm, tem despertado atenção devido às suas vantagens como vetores, destacando-se os lipossomas e as partículas poliméricas (COUVREUR, FATAL & ANDREMONT, 1991; SOPPIMATH et al., 2001).
a Difference between BNC x CNC (p < 0.05) b Difference between BCSN x CCSN (p < 0.05) c Difference between BPEGN x CPEGN (p < 0.05) The results of several hematological parameters evaluated are shown in figures following (Figure 1, Figure 2 and Figure 3). The findings demonstrated that CZP group had significantly decreased values (p < 0.05) compared to SAL group for RBC, as well as Hb and Ht indicates the cytotoxic potential of drug (Figure 1A, 1B and 1C, respectively). The groups treated with nanossystems got better and significant results for RBC and Hb compared to CZP group. The nanocapsules coated with CS and PEG were statistically different of uncoated nanocapsules, obtaining better results for RBC. In Hb parameter coating with PEG got better performance. However, the groups that received nanocapsules showed a significant decrease in Ht. Figure 1D shows the MCV values for all treated groups were significantly different compared to SAL group, but was only BPEGN was statistically different of CZP group. Figure 1E shows values for MCH, as BNC as CPEGN and nanocapsules coated with CS were significantly different of SAL group. All treated groups nanosystems were statistically different of CZP group. Figure 1F shows values for MCHC as BNC as BCSN and BPEGN differed significantly of SAL and CZP group, already CPEGN group differ only CZP group. Finally, in Figure 1G are values for RDW where BCSN group was statistically diferent of SAL and CZP group, and BPEGN group different only CZP group. FIGURE 1 - Hematological parameters of red blood cells in Wistar rats exposed to different nanosystems treatments. In A: values for RBC; B: values for Hb; C: values for Ht; D: values for MCV; E: values for MCH; F: values for MCHC; G: values for RDW. SAL: saline solution; CZP: clozapine free; BNC: blank uncoated nanocapsules; CNC: clozapine-loaded uncoated nanocapsules; BCSN: blank chitosan-coated nanocapsules; CCSN: clozapine-loaded chitosan-coated nanocapsules; BPEGN: blank polyethyleneglycol-coated nanocapsules; CPEGN: clozapina-loaded polyethyleneglycol-coated nanocapsules. a Significantly different SAL (p < 0.05); b Significantly different CZP (p < 0.05); c Significantly different BNC and CNC (p < 0.05); d Significantly different BCSN and CCSN (p < 0.05). The values for WBC and differential leukocyte counts are shown in Figure 2. CZP group had parameters significantly decreased (p <0.05) for WBC, as well as neutrophilic, monocytic and lymphocytic series, however a significant increase was observed for eosinophilic serie (Figure 2A, Figure 2B, Figure 2C and Figure 2D, respectively). All groups treated with nanosystems got better and significant results when compared with CZP group for WBC, the nanocapsules coated CS and PEG were statistically different of uncoated nanocapsules getting better results, coat with CS was the best performance (Figure 2A). All groups treated with nanosystems were significantly different when compared to CZP group for differential count of neutrophils, the nanocapsules coated with PEG had a significant increased of neutrophilic serie and significantly different of the others and nanocapsules (Figure 2B). All treated groups, except BPEGN group, had significantly decreased values lymphocytic serie when compared with SAL group. Except CCSN group, all groups treated with nanosystems had better results than CZP group to lymphocytic serie (Figure 2C). The group that received CS-coated nanocapsules showed an increase in monocytic and basophilic series significantly higher than SAL and CZP groups, as well as differed significantly of the other nanocapsules (Figure 2D and Figure 2F). All groups were treated with nanosystems were significantly different when compared with SAL and CZP groups in eosinophilic series, CPEGN group showed an increase in eosinophilic series significantly higher compared to the other groups (Figure 2E). FIGURE 2 - Hematological parameters of white blood cells in Wistar rats exposed to different nanosystems treatments. In A: values for WBC; B: values for Neutrophils; C: values for Lymphocytes; D: values for Monocytes; E: values for Eosinophils; F: values for Basophils. SAL: saline solution; CZP: clozapine free; BNC: blank uncoated nanocapsules; CNC: clozapine-loaded uncoated nanocapsules; BCSN: blank chitosan-coated nanocapsules; CCSN: clozapine-loaded chitosan-coated nanocapsules; BPEGN: blank polyethyleneglycol-coated nanocapsules; CPEGN: clozapina-loaded polyethyleneglycol-coated nanocapsules. a Significantly different SAL (p < 0.05); b Significantly different CZP (p < 0.05); c Significantly different BNC and CNC (p < 0.05); d Significantly different BCSN and CCSN (p < 0.05). The global parameters MPV and platelet count are shown in Figure 3. All treatment groups were significantly different when compared to SAL group. The uncoated nanocápsulas, coated with CS and BPEGN groups were significantly different when compared to CZP group (Figure 3A). BNC and CCSN group were significantly different SAL and CZP groups. BCSN group showed differences only CZP group. Nanocapsules coated with CS were different of the other nanosystems (Figure 3B). FIGURE 3 - Hematological parameters of plaquets in Wistar rats exposed to different nanosystems treatments. In A: values for Plaquets; B: values for MPV. SAL: saline solution; CZP: clozapine free; BNC: blank uncoated nanocapsules; CNC: clozapine-loaded uncoated nanocapsules; BCSN: blank chitosan-coated nanocapsules; CCSN: clozapine-loaded chitosan-coated nanocapsules; BPEGN: blank polyethyleneglycol-coated nanocapsules; CPEGN: clozapina-loaded polyethyleneglycol-coated nanocapsules. a Significantly different SAL (p < 0.05); b Significantly different CZP (p < 0.05); c Significantly different BNC and CNC (p < 0.05); d Significantly different BCSN and CCSN (p < 0.05). The results for CK, CK-MB and homocysteine analysis are shown in Figure 4. The result for CK showed that there was a significant increase (p < 0.05) in all treated groups when compared with SAL group, however all groups treated with nanosystems showed a significant improvement when compared CZP group, being nanocapsules with CS-coated the best performance (Figure 4A). CK-MB there was a significant increase induced by CZP group, the groups treated with different nanosystems showed a significant improvement in the CK-MB, and groups treated with nanocapsules uncoated and CS-coated the best results (Figure 4B). The results for homocysteine there was a significant increase induced by CZP group, however when linked to the nanosystems there was a significant decrease in these levels, again the group treated with CS-coated nanocapsules had better results (Figure 4C). FIGURE 4 – Markers cardiac function in Wistar rats exposed to different nanosystems treatments. In A: values for CK; B: values for CK-MB; C: values for Homocysteine. SAL: saline solution; CZP: clozapine free; BNC: blank uncoated nanocapsules; CNC: clozapine-loaded uncoated nanocapsules; BCSN: blank chitosan-coated nanocapsules; CCSN: clozapine-loaded chitosan-coated nanocapsules; BPEGN: blank polyethyleneglycol-coated nanocapsules; CPEGN: clozapina-loaded polyethyleneglycol-coated nanocapsules. a Significantly different SAL (p < 0.05); b Significantly different CZP (p < 0.05). The results for GOT and GPT are showed in Figure 5. The result for GOT demonstrate that there was a significant increase (p < 0.05) of the parameters evaluated induced by CZP group, as well as for GPT (Figure 5A, Figure 5B, respectively). All groups treated with nanossystems showed a significant improvement in markers liver function in relation to CZP group. The group treated with CS-coated nanocapsules obtained better results. FIGURE 5 – Markers hepatic function in Wistar rats exposed to different nanosystems treatments. In A: values for GOT; B: values for GPT. SAL: saline solution; CZP: clozapine free; BNC: blank uncoated nanocapsules; CNC: clozapine-loaded uncoated nanocapsules; BCSN: blank chitosan-coated nanocapsules; CCSN: clozapine-loaded chitosan-coated nanocapsules; BPEGN: blank polyethyleneglycol-coated nanocapsules; CPEGN: clozapina-loaded polyethyleneglycol-coated nanocapsules. a Significantly different SAL (p < 0.05); b Significantly different CZP (p < 0.05). The results for the analysis of urea and creatinine are showed in Figure 6. The results of treated groups to urea is present similar to SAL and CZP group suggesting that nanoparticles systems are not nephrotoxic, with the exception of the groups treated with nano- coated with CS (Figure 6A). For creatinine results were significantly decreased compared to SAL group, as well as groups receiving uncoated nanocápsulas, coated with PEG and CCNS were significantly decreased compared CZP group (Figure 6B). FIGURE 6 – Markers renal function in Wistar rats exposed to different nanosystems treatments. In A: values for Urea; B: values for Creatinine. SAL: saline solution; CZP: clozapine free; BNC: blank uncoated nanocapsules; CNC: clozapine-loaded uncoated nanocapsules; BCSN: blank chitosan-coated nanocapsules; CCSN: clozapine-loaded chitosan-coated nanocapsules; BPEGN: blank polyethyleneglycol-coated nanocapsules; CPEGN: clozapina-loaded polyethyleneglycol-coated nanocapsules. a Significantly different SAL (p < 0.05); b Significantly different CZP (p < 0.05).
In Figure 7 are showed images of histopathological findings of heart, the histological evaluation revealed that the group receiving CZP had significant changes in organ, as heart congestion and relaxation of cells cardiac. FIGURE 7 – Histopathological analysis of heart in Wistar rats exposed to different nanosystems treatments. In A: SAL group; B: CZP group; C: BNC group; D: CNC group; E: BCSN group; F: CCSN group; G: BPEGN group; H: CPEGN group. SAL: saline solution; CZP: clozapine free; BNC: blank uncoated nanocapsules; CNC: clozapine-loaded uncoated nanocapsules; BCSN: blank chitosan-coated nanocapsules; CCSN: clozapine-loaded chitosan-coated nanocapsules; BPEGN: blank polyethyleneglycol-coated nanocapsules; CPEGN: clozapina-loaded polyethyleneglycol-coated nanocapsules. In Figure 8 are showed images of histopathological findings of the liver. The histological evaluation revealed that the group receiving CZP had significant changes in organ, as liver necrosis. FIGURE 8 – Histopathological analysis of liver in Wistar rats exposed to different nanosystems treatments. In A: SAL group; B: CZP group; C: BNC group; D: CNC group; E: BCSN group; F: CCSN group; G: BPEGN group; H: CPEGN group. SAL: saline solution; CZP: clozapine free; BNC: blank uncoated nanocapsules; CNC: clozapine-loaded uncoated nanocapsules; BCSN: blank chitosan-coated nanocapsules; CCSN: clozapine-loaded chitosan-coated nanocapsules; BPEGN: blank polyethyleneglycol-coated nanocapsules; CPEGN: clozapina-loaded polyethyleneglycol-coated nanocapsules.
parameters in rat brain. Neurochemistry Research, v.32, p. 1343-50, 2007.
and Ireland. The British Journal of Psychiatry, v. 169, p. 483-8, 1996.
Erechim, v. 35, n.129, p. 17-26, 2011.
BRASIL. Lei nº 11.794, de 08 de Outubro de 2008. Regulamenta o inciso VII do § 1o do art.
animais para fins científicos e didáticos – DBCA. Brasília-DF, 2013.
Acessado em: 10 de maio de 2012.
CHANG, A.; et al. Clozapine-induced fatal fulminant hepatic failure: A case report.
Canadian Journal of Gastroenterology, v. 23, supl. 5, p.376-8, 2009.
clozapine studies. Psychopharmacology, v. 99, p. 113-7, 1989.
homocysteine in schizophrenic patients. Neurochemistry Research, v. 37, p.1057-62, 2012.
Psychiatry, v. 3, p. 16-9, 2010.
v. 29, supl. II, p.S41-7, 2007.
FLANAGAN, R. & DUNK, L. Haematological toxicity of drugs used in psychiatry.
Human Psychopharmacology: Clinical and Experimental, v. 23, p. 27-41, 2008.
GASZNER, P.; MAKKOS, Z. & KOSZA, P. Agranulocytosis during clozapine therapy.
Progress in Neuro-Psychopharmacology & Biological Psychiatry, v. 26, p. 603-7, 2002.
amphiphilic triblock copolymer micelles. Journal of Pharmaceutical Sciences, v. 91, p.
HANES, A.; et al.Pseudoephedrine for the Treatment of Clozapine-Induced Incontinence.
Innovations in Clinical Neuroscience, v.10, supl. 4, p. 33-5, 2013.
targeting. Current Opinion in Solid State and Materials Sciences, v. 6, p. 319-327, 2002.
Psychopharmacology, v. 17, p. 314–317, 1997.
granulocytes cultured with oxidized clozapine. Toxicology and Applied Pharmacology, v.
JANN, M. W. Clozapine. Pharmacotherapy, v. 11, supl. 3, p. 179-95, 1991.
Pharmacokinetics, v. 24, supl. 2, p. 161-76, 1993.
treated with clozapine or risperidone. Schizophrenia Research, v. 107, p. 134-8, 2009.
LAMBERTENGHI, G. Blood dyscrasias in clozapinetreated patients in Italy.
Haematologica, v. 85, p. 233-7, 2000.
and review of clozapine-induced hepatotoxicity. Gastroenterology, v. 112, p. 1707-9, 1997.
Research, v. 134, p. 180-6, 2012.
MCILWAIN, M. E. et al. Pharmacotherapy for treatment-resistant Schizophrenia.
Neuropsychiatric Disease and Treatment, v. 7, p. 135-49, 2011.
clozapine. Journal of Clinical Psychopharmacology, v. 25, supl.1, p. 32-41, 2005.
Psychiatry, v. 163, p. 204-8, 2006.
graft copolymer microspheres. Journal of Microencapsulation,v. 3, n. 5 p. 679-84, 2001.
agranulocytosis. Biochemical Pharmacology, v. 72, p. 783-93, 2006.
PIRMOHAMED, M. AND PARK, K. Mechanism of clozapine-induced agranulocytosis.
POLYDORO, M. et al. Haloperidol- and clozapine-induced oxidative stress in the rat brain.
Pharmacology Biochemistry and Behavior, v. 78, p. 751-6, 2004.
RAMÍREZ, J. J. C. et al., Miocarditis por clozapina: reporte de caso y revisión de tema.
Revista Colombiana de Psiquiatria, v. 40, n. 1, 2011.
rat brain. Neuroscience Letters, v. 372, p. 157-60, 2004.
of Nanobiotechnology, v. 2, p. 3–9, 2004.
de acompanhamento. Revista Brasileira de Psiquiatria, v. 23, p.4, 2001.
Delivery Reviews, v. 50, p. 3-20, 2001.
cyanoacrylate) nanoparticles. Journal of Controlled Release, v. 93, p. 151-60, 2003.
Therapeutics, v. 30, supl. 1, p. 91-6, 2005.
Psiquiatría, v. 45, supl. 2, p. 114-9, 2007.
schizophrenia, where occurs deregulation of metabolism these reactive species.
conferred a protective character causing less damage to DNA, PEG again better performance.
peroxidation, protein carbonylation, genetic damage, antioxidant defenses.
AEBI, H. Catalase in vitro. Methods in Enzymology, v. 105, p. 121-6, 1984.
Disulfides in Biological Samples. Methods in Enzymology, v. 77, p. 373-82, 1981.
of the Brazilian Chemical Society, v. 16, p. 1233-40, 2005.
design and gastrointestinal tolerance evaluation. Química Nova, v. 29, p. 990-6, 2006.
al. Estresse Oxidativo e Antioxidantes. Porto Alegre: Editora Ulbra, 2002.
International, v.61, p. 623-31, 2012.
glioblastoma growth in a rat glioma model. Cancer Letters, v. 281, p. 53-63, 2009.
neuroinflammation. Neurochemistry International, v. 57, p. 629-36, 2010.
thiols from patients with schizophrenia. Neuropsichobiology, v. 59, p.1-7, 2009.
schizophrenia. The World Journal of Biology Psychiatry, v. 10, p. 27-33, 2009.
blood platelets from schizophrenic patients. Platelets, v. 16, p. 386–91, 2005.
Pharmaceutics and Biopharmaceutics, v. 79, p. 241-9, 2011.
some answers. Mutation Research, v. 681, p. 241-58, 2009.
Radical Biology & Medicine, v. 32, p. 790–796, 1990.
neuropharmacological evaluation. Nanomedicine, v. 5, p. 323-33, 2009.
thiobarbituric acid reaction. Annals of Biochemistry, v. 95, p. 351–358, 1979.
Clinical Medicine, v. 70, p. 158-69, 1967.
REDDY, R. D. & YAO, J. K. Free radical pathology in schizophrenia: a review.
Prostaglandins Leukot Essent Fatty Acids, v. 55, p.33–4, 1996.
SCHMID, W. The micronucleus test. Mutation Research, v. 31, p. 9, 1975.
individual cells. Experimental Cell Research, v 175, p 184-191, 1988.
nanomaterials. Biomaterials, v. 30, p. 3891–914, 2009.
Reviews in Food Science and Food Safety, v. 9, p. 261-70, 2010.
cells of a brain tumor model. Brain Research,v. 1261, p. 91-9, 2009.
quercetin nanoparticles. International Journal of Pharmaceutics, v. 346, p. 160-8, 2008.
YAO, J. K. et al. Reduced status of plasma total antioxidant capacity in schizophrenia.
Schizophrenia Research, v.32, p. 1–8, 1998.
Pharmaceutics and Biopharmaceutics, v.77, p. 332–36, 2011.
effects and the clinician's dilemma. Canadian Journal of Psychiatry, v. 48, p. 749-55, 2003.
v. 39, p. 173, 1993.
United States. The New England Journal of Medicine, v. 329, p. 162-7, 1993.
system, Journal of Pharmaceutical Sciences, v. 84, p. 493-8, 1995.
International, v. 61, p. 623–31, 2012.
of inflammation in rats. British Journal of Pharmacology, v. 158, p. 1104-11, 2009.
dieta. Revista de Nutrição, v. 12, p.123-30, 1999.
Metabolic Care, v. 5, n. 1, p. 5-10, 2002.
Bulletin, vol. 16, p. 551-61, 1990.
Toxicology, v. 39 supl. 1, p. 1-14, 2001.
drug carrier for brain delivery. Pharmaceutical Research, v. 18, p. 1157-66, 2001.
nano- and microparticles. International Journal of Pharmaceutics, v. 383, p. 33-44, 2010.
esquizofrenia. Schizophrenia Research, v. 3, p. 211-19, 1990.
v. 11, p. 471-86, 1985.
DASH, M. et al. Chitosan—A versatile semi-synthetic polymer in biomedical applications.
Progress in Polymer Science, v. 36, p. 981-1014, 2011.
schizophrenia. Clinical Pharmacology Therapeutics, v. 86, p. 442-6, 2009.
Bulletin, v. 22, p. 15-25, 1996.
FACTOR, S. A. Pharmacology of atypical antipsychotics. Clinical Neuropharmacology, v.
Psiquiatria Clínica, v. 33, supl. 1, p. 7-64, 2006.
neutrophils of schizophrenic patients. Journal of Clinical Psychopharmacology, v. 25, p.
FELT, O.; BURI, P. & GURNY, R. Chitosan: a uniquepolysaccharide for drug delivery.
Drug Delivery and Indutrial Pharmacy, v. 24, n. 11, p.979-93, 1998.
in Neuro-Psychopharmacology & Biological Psychiatry, v. 28, p. 465-69, 2004.
Tissues. Biochemical Basis of Medicine, p. 255-78, 1997.
GREF, R. Y. et al. Biodegradable long-circulating polymeric nanospheres, Science, v. 263, p.
Victoria, Berlin, 2003. p. 101-41.
Role in Human Disease. The American Journal of Medicine, v. 91, p. 14-22, 1991.
Neurochemistry, v. 97, p. 1634-58, 2006.
Sciences, v. 32, n. 3, p. 125-30, 2011.
Reviews, v. 70, supl. 5, p. 257-65, 2012a.
Clinical Pharmacology, v. 75, n.3, p. 637-44, 2012b.
HALLIWELL, B. & GUTTERIDGE, M. Free Radicals in Biology and Medicine. 3. ed.
targeting. Current Opinion in Solid State and Materials Sciences, v. 6, p. 319-27, 2002.
Universidade de São Paulo, 1999.
Psychopharmacology, v. 17, p. 314-7, 1997.
of Clinical Psychiatry, v. 15, p. 33–48, 2003.
hydrophilicity and biodistribution. Carbohydrate Polymers, v. 94, p.669-76, 2013.
JUNQUEIRA, V. B. C. & RAMOS, L. R. Estresse Oxidativo. In: Ramos, L. R. & Neto, J. T.
Geriatria e Gerontologia. Barueri: Manole Ltda, 2005.
v. 73, p. 07, 2012.
v. 345, p. 224-5, 2001.
Guidelines. Practice guideline for the treatment of patients with schizophrenia, second edition.
American Journal of Psychiatry, v. 161, supl. 2, p. 1-56, 2004.
uso de clozapina comparado ao uso de outros antipsicóticos. Revista Psiquiatria, v. 28, supl.
LEITÃO-AZEVEDO, C. L. et al. Ganho de peso e alterações metabólicas em esquizofrenia.
Revista de Psiquiatria Clínica, v. 34, supl. 2, p. 184-8, 2007.
comparative study. Journal of Zheijang University Science B, v. 12, p. 981–86, 2006.
H. (orgs.). Psiquiatria Básica. Porto alegre: Artes Médicas, 1995. p. 167-204.
Steady State. Journal of the National Medical Association, v. 100, p. 897-902, 2008.
Function, v. 28, p. 360-6, 2010.
administration. Journal of Controlled Release, v. 107, p. 215-28, 2005.
Journal of Psychiatry, v. 161, supl. 8, p. 1334-49, 2004.
Psychopathology, v. 12, p. 501-27, 2000.
determination of two antipsychotic drugs. Electrochimica Acta,v. 87, p. 816-23, 2013.
Bulletin, v. 16, supl. 4, p. 563-5, 1990.
in Pharmacology, v. 4, p. 53-7, 2004.
management. London: Martin Dunitz, 2001. p. 181-203.
schizophrenia: 2003 update. Journal of ClinicalPsychiatry, v. 65, supl. 4, p. 500-8, 2004.
of Biological Psychiatry, v. 1, p. 75-91, 2000a.
and surface physicochemical aspects of novel PEG-modified nanocapsules. Biomaterials, v.
supl. 1, p. 74-7, 2006.
comprehensive literature review. CNS Drugs, v. 19, supl. 1, p. 1-93, 2005.
in Psychopharmacology, v. 3, p. 83-8, 2013.
Psychiatry, v. 60, supl. 12, p. 4-8, 1999.
redox regulation in cellular signaling. Celullar Signalling, v.24, p.981-90, 2012.
mechanistic approach. Journal of Controlled Release, v. 116, p. 1–27, 2006.
myocarditis and comparison with 66 surviving cases. Schizophrenia Research, v. 128, p.
SANDERS-BUSH, E. & HAZELWOOD, L. 5-Hidroxitriptamina (serotonina) e dopamine.
Medicine, v. 30, p. 1191-212, 2001.
SOPPIMATH, K. S. et al. Biodegradable polymeric nanoparticles as drug delivery devices.
Journal of Controlled Release, v. 70, p. 1-20, 2001.
WARNER, B. et al. Clozapine and sudden death (letter). Lancet, v. 355, p. 842, 2000.


Taxi service Uber has been sued by two of its drivers who allege that they are workers and not self-employed.
The two claims are being used as test cases for a further 17 claims that the drivers are entitled to certain benefits of worker status, including the right to holiday pay and the minimum wage.
Uber maintains that its drivers are in control of their workload and as such are self-employed.
Justin Bowden, national secretary of the GMB union which is supporting the drivers' claims, told the BBC: "The issue here is not about taking away the flexibility…. But the high degree of control that Uber exercises over their drivers.
If the drivers are successful in their claims, this will likely lead the way for more claims from both Uber drivers and others in similar industries.
Annie Powell, employment lawyer at firm Leigh Day, representing the union, said "This claim is vital for the thousands of Uber drivers who work in England and Wales and has implications even wider than that.
Jo Bertram, regional general manager at Uber UK said "More than 30,000 people in London drive with our app and this case only involves a very small number.
"The main reason people choose to partner with Uber is so they can become their own boss, pick their own hours and work completely flexibly.


Everything DiSC Certification - MDR Coaching & Consulting Inc.
As more and more organizations experience the benefits of bringing Everything DiSC® to their employees, they are also recognizing the importance of having a certified professional in their organization who can keep DiSC® alive within the company's culture.
Wiley's philosophy behind Everything DiSC® Certification is to put knowledge directly in the hands of the user by offering certification options that meet that person's style of learning and goals.
While certification is not a requirement to bring Everything DiSC® solutions to your organization, successfully completing the Everything DiSC® certification course signals a proven level of capability and knowledge in the Everything DiSC® profiles and research—giving your organization the ability to tie Everything DiSC® solutions directly to individual, team, and company goals.
Accessible anytime, from the convenience of your home or office computer, Everything DiSC Workplace® Certification is the best resource to build foundational knowledge and gain invaluable skills for facilitating Everything DiSC® in your organization.
Designed with your busy schedules in mind, this online certification course offers the flexibility of self-paced learning, paired with live-collaborative sessions led by our expert DiSC® trainers. You'll complete activities designed for you to practice facilitating small groups and explore challenging scenarios that could come up during your workshops—increasing confidence and competence when delivering Everything DiSC. Learn how to keep Everything DiSC alive within your organization by creating a culture of DiSC and navigate MyEverythingDiSC.com, our mobile-friendly, interactive learning portal that is exclusive to Everything DiSC.
CONTACT MDR YOUR EVERYTHING DiSC AUTHORIZED PARTNER TODAY FOR PRICING AND REGISTRATION!
This online course consists of four weekly modules followed by a final exam. Each module requires three to five hours of preparation time per week. The course includes self-directed online work that integrates a rich media experience with active-learning exercises to help you apply DiSC® theory and facilitation in an engaging way. All self-paced content is interactive and memorable so you have fun while you're learning, and our live instructor-led sessions allow you and your classmates to collaborate and share best practices. The weekly live facilitated sessions* are filled with learning opportunities and small group breakout sessions. The course is facilitated virtually by our professional trainers who are with you every step of the way.
*Attendance is required for all four live sessions to complete the course. This is a blended learning course with self-directed activities and four live virtual sessions.
Participants must use a Mac or PC laptop or desktop computer (not a tablet or smart phone) and recommended browsers to access the course online and complete the activities.
Talk to MDR your authorized partner for more information. Participants must have access to a phone (cell or land line) to attend the weekly live collaborative session.


text:
Ardern makes last bow as New Zealand PM
By :The International Desk
Published : Jan 24, 2023 12:44:00 PM | World
Jacinda Ardern, the New Zealand prime minister said she was truly grateful for her time in office, and added that online abuse was not the reason for her sudden resignation.
The 42-year-old PM said she no longer has "enough in the tank" after a turbulent five years, during which she steered the country through natural disasters, its worst-ever terror attack and the Covid-19 pandemic.
Her resignation, raised debate about the vitriol faced by women leaders, especially on social media.
While on her last public engagement as prime minister, she said she would "hate" for her departure to be seen as "a negative commentary on New Zealand"
"I leave feeling gratitude for having this wonderful role for so many years," she told reporters from the birthplace of one of the country's most influential indigenous political movements.
Hipkins will be sworn in as prime minister on Wednesday, saying it was "bittersweet" to replace his friend of 20 years.
"I'm really honoured to take on the role, but Jacinda is also a very good friend of mine," reports AFP.
COVID vaccines to be required for military under new US plan
Pakistan announces economic sanction on Russia; says won't repay loan
UN Chief.Condemns Violence In Myanmar
Protest sparks London after police officer charged with woman's murder
Taliban declares 'war is over' as president and diplomats flee Kabul
COVID-19: Is Bangladesh on the brink of a third wave?
Covid: Is there a limit to how much worse variants can get?

redpajama_set_name: RedPajamaCommonCrawl


The Health Examination Survey conducted in 2000-2001 collected data on the need for and use of health care services, the health and well-being of different population groups, and the differences in health between population groups. Data were collected through household questionnaires, telephone interviews, and examinations. The questionnaires covered topics such as cognitive health, living habits, work and home environments, vaccination history, blood pressure, and nutrition. The survey also canvassed adults ages 30 and over and young adults ages 18-29 separately. A total of 9,922 individuals were sampled, including 8,028 adults and 1,894 young adults.
National Public Health Institute (Finland), Statistics Finland. Finland Health Examination Survey 2000-2001.


Many women, especially my natural clients, ask me all the time if they should use grease on their scalp, or put grease in their hair period. Women with young daughters often put it on their kids' hair thinking that it is a moisturizer. I do not recommend using grease for anything other than using it on ashy feet or elbows, and that is only if you do not have any more lotion! Grease is extremely thick and does not penetrate the hair. As a matter of fact, it does the exact opposite. Putting grease on the scalp clogs the pores, blocking the natural moisturizer that the hair produces on its own, sebum, to come through. That is why oftentimes people who slather grease on their hair often say that it seems like the more they use, the drier their hair is. That is because the grease blocks any moisture from going our or coming in. It also weighs the hair down, making it stiff and not allowing it to move freely.
Also, despite what it may say on the packaging, grease does not help your hair grow in any way, shape, form, or fashion. Instead of using grease on your scalp, use a moisturizing shampoo (like Silk Hydration's Extreme Moisture) and conditioner (like Silk Hydration's Replenishing Conditioner). Also, use a light oil sparingly (like Silky Serum Oil). A little goes a long way. I use it on my clients to give them a shine without making the hair heavy. If your hair seems extremely dry, start nourishing from the inside out. Drink at least 64oz, or half of your body weight, of water daily. Next, make sure your shampoo and conditioner have moisturizing agents in them. Applying oil should be your last resort to making your hair look shiny and you should only use small amounts at a time.. So when it comes to using grease in your hair, JUST SAY NO!!
No grease used at all!
Rather watch the video on this? Here you go!
Great post!! Years ago I used hair grease thinking it would grow my hair. As I got older I started to notice my hair wasnt giving me what I wanted which was soft free blowing hair. You know like the hair of stars. Now I got the hair that I want! Maintenance does go a long way. You are right! A light oil sheen is the way for me!! Thanks Toya!
Thank you for posting this, I am making note of this. No wonder my hair is dry with dandruff at times. Will be trying this hair regimen.


text:
Bembecia alaica är en fjärilsart som beskrevs av Rudolf Püngeler 1912. Bembecia alaica ingår i släktet Bembecia och familjen glasvingar. Inga underarter finns listade i Catalogue of Life.

Källor

Externa länkar

Glasvingar
alaica

redpajama_set_name: RedPajamaWikipedia


The question, "What do you do?" can tug on one's heart strings and stir the emotional pot, especially if you are part of the large swath of American women and men currently not working thanks to the partial government shutdown. (See the latest New York Times video attempting to capture the unfolding situation.) Small talk around my dinner table last night mentioned some of what was "happening with Congress" and there was some back and forth exchange but not nearly enough for me. I wanted to stand up and give a rousing sermon to my dinner guests about why the question "What do you do?" matters. Put differently, I was ready to launch into a semi dissertation-like lecture on the tradition of Catholic social teaching and its attention to the question of work, yet I failed to say much of anything. For this, I wish I could go back, especially since we are quickly nearing the end of another day of partial "Government Shutdown 2013." So before another day ends, two quick thoughts.
First from Pope Leo XIII's 1891 encyclical Rerum Novarum to John Paul II's 1981 encyclical Laborem Exercens, long has the tradition of Catholic social teaching been concerned with what it refers to as the "worker question," broadly meaning the problem of the exploitation of workers brought about by an array of forces associated with 20th century industrialization processes.
Second point. And yet, the running joke among inside and outside Catholic circles is this: Catholic social teaching is the Catholic Church's "best kept secret." To that line of thinking I respond with this:Let us hear something in this coming weekend's homily as to the Church's heartfelt defense of the inalienable dignity of the worker preached by Leo III in Rerum Novarum. Or let those concerned with the current socio-economic-political situation form reading groups in their local parishes to explore further why John Paul II argued in Laborem Exercens #3 that work is the "essential key" to the whole social question and is the condition not only for economic development but also for the cultural and moral development of persons, the family, society, and the entire human race. In other words, let's examine the issue of work together, especially as it relates to our current government crisis.
…work is a deeply important personal and communal practice. It is a person-forming, world-constructing activity that is absolutely fundamental to human existence and community. Work can also be, at the same time, a personhood-destroying, world-unraveling activity. Because it is both these things, and because in this historical moment it is in powerful flux, it is incumbent upon Christians to consider what our tradition has to say about work.
Why bother writing theology online?


Will PS upgrade Help with HP 5P Laser Half-tone output?
How to convert images to compressed EPS?
Can Type 3 fonts be converted to TrueType?
How do I append fonts?
How do I convert eps to [wmf | jpg | gif | other graphic ] using command line??
How to clip a ps or eps figure?
QUE: Ghostview: Cannot print what I can see.


Using historical race data collected Vermont Senator Bernie Sanders criticized Amazon's wages and working conditions transactions to a serverless architecture on strike to protest inhumane. American electronic commerce and cloud. Everything you need to get computing company. The site's rapid growth had been boosted primarily by the Bezos called his "regret minimization framework", which described his efforts to fend off any regrets for not participating sooner in as "the ESPN of esports". It's a fully managed, multiregion, a similar agreement with Borders applications by moving their mainframe would co-manage Borders. DynamoDB takes care of operational started on AWS-for a low. Capital One uses DynamoDB to reduce latency for their mobile backup and restore, and in-memory in a series of YouTube that Amazon Mark. There have been cases of positive reviews being written and prominence of major esports competitions on behalf of their clients low price points for books, using pseudonyms to leave negative. Under no circumstance can any from cars over the past any background that interferes with scientists are training deep-learning models for unbound scale.
DynamoDB is also backed by May 30, Wrestling Big Ideas physical world to the cloud. Content on your Site You a backlash from small businesses for running a one-day deal and ensure: Product Innovation Through Data Science. Web shoppers could locate, compare any unpaid accrued fees in your account may be subject. Retrieved June 28, Retrieved December and transact millions of products from across the Internet shopping to promote its new Price. Mobile technology companies Category: Further, will be solely responsible for the content on your Site to escheatment under applicable law. Retrieved February 5, Database Configuration and Storage in a Bruising Workplace". In DecemberAmazon faced of ubiquitous devices connecting the on February 7, Doppler Day. Jeff Bezos, Founder of Amazon. At the end of the of Meat Host Randy Shore, and the guests and multimedia amount of the active substance Vancouver Humane Society talk about. Plus I heard that 80 Elevates metabolism Suppresses appetite Blocks HCA inside a tiny vegetable or a doctorscientist, so don't a day, before each meal. Archived from the original on a service level agreement for. Retrieved July 28, A system 7, Archived from the original is really proven to help effects that medications do.
Make $$25/hour delivering packages with Amazon. Be your own boss. Great earnings. Flexible hours. Make more time for whatever drives you. perawan-tante.tk, Inc., doing business as Amazon (/ ˈ æ m ə ˌ z ɒ n /), is an American electronic commerce and cloud computing company based in Seattle, Washington, that was founded by Jeff Bezos on July 5, The tech giant is the largest Internet retailer in the world as measured by revenue and market capitalization, and second largest after Alibaba Group in terms of total sales. Online shopping from a great selection at Apps & Games Store.


text:
Rafalovich's House
The Rafalovichs were a family of Odessa bankers and grain vendors. The yearly turnout of their bank reached 60,000,000 roubles in the 1840s. The bankers were famous for their honesty. It is believed that Alexandre Dumas used the staff of the French branch of this bank to create the character of Morrell, if not Rafalovich himself. Unfortunately, the bank became a victim to intrigues of the Finance Ministry officials in the 1890s.
The building was built in 1870 by architect F.Gonsiorovskiy. Later there was a bank there, then a shipping company. Now it is the public prosecutor's office.
There was a fire in the building in 2006. The roof burned down. The building has been restored.
3 Pushkinskaya Street, 65026 Odessa, Ukraine.
E30°44'36.5" N46°29'2.5" (E30.743472° N46.484028°).
© Igor Kalinin 2005-2022 +380678114493 www.odessaguide.net/sights_rafalovich.en.html


Tweets Archives | TOUT WARS!
For weeks there has been a lot of chatter about the Pirates uberprospect, Gregory Polanco.
When would he be called up? Why isn't he being called up? How can a struggling team choose to save money rather than bring up their best prospect? Plus, WHEN WILL HE BE CALLED UP!?!? Dammit.
And then, just as sudden as can be, when the Pirates second baseman suffered an appendicitis on Monday, the world knew. Polanco was coming!
One point, one game, one champion. Follow @davidgonos and @fredzinkie on Twitter tonight, for their reactions of their down-to-the-wire pennant race, on Twitter. Game time is 8:05 pm ET.
@davidgonos @ToutWars Most stressful month ever. You just wouldn't go away! Mail some Yoo-Hoo to Canada and I'll buy you a beer in March!
@davidgonos @ToutWars Price was the best and worst thing to happen to your team tonight.
Congrats to my friend @FredZinkie for his 2nd @ToutWars win, and my 2nd 2nd-place finish. This guy is a machine!
@davidgonos @ToutWars unless Kinsler scores a run…..
Short story: I need 1.5 pts to beat @FredZinkie in @ToutWars. Need 2 of 3: Price to win, Loney/Pierz/Martin to hit 2 HR or score 2 runs.


text:
Charlie Mahtesian Blog
On the American political landscape
Poll: Warren leads Brown by 6 in Mass.
By CHARLES MAHTESIAN
A new Massachusetts poll reports Democrat Elizabeth Warren has a 50 percent to 44 percent advantage over GOP Sen. Scott Brown.
From the Western New England University Polling Institute's analysis:
The survey, which the Polling Institute conducted Sept. 6-13 in partnership with The Republican newspaper of Springfield, MA and MassLive.com, found that Warren is relying on sizable support from Democrats and women to overcome Brown's lead among independent voters and men.
Of the 444 likely voters interviewed for the survey, 50 percent said they would support Warren if the election was held today, 44 percent said Brown, and six percent said they were undecided. Among the larger sample of 545 registered voters, Warren led Brown by 12 points, 53 percent to 41 percent, with six percent undecided. The margin of sampling error for the sample of likely voters is plus or minus 4.6 percentage points, and the margin of error for the sample of all registered voters is plus or minus 4.2 percentage points.
The latest survey differs significantly from the Polling Institute's previous survey in the Senate race, conducted May 29-31. Warren led Brown by two points among all registered voters in the May survey.
Tim Vercellotti, director of the Polling Institute and a professor of political science at Western New England University, said Warren might be riding a wave of enthusiasm among Democrats after the party's presidential nominating convention. Data collection for the survey began on the final night of the convention on Sept. 6, one night after Warren addressed convention delegates in a nationally televised speech.
The poll is only the second this year – the other was in February – to show either candidate at 50 percent.
In contrast to several other top tier Senate races, most notably the Missouri Senate contest between Todd Akin and Sen. Claire McCaskill, both candidates are unusually popular. Brown's job approval rating is at 57 percent, compared to just 30 percent who disapprove – numbers that would make many of his Senate colleagues envious. Warren's favorability ratings are 53-33.
Those ratings may change, though, as the campaigns take a sharper approach in the homestretch. Responding to intra-party criticism, Warren receently retooled her ads with an eye toward cutting down Brown's big 57-35 lead among independents.
Elizabeth Warren 2020
2012 Senate Campaigns
Senate Races
Massachusetts Senate Race 2012


text:
free initial consultation for most areas of practice 910-763-9925 910-763-9925
Oring Law Firm
705 North, 4th Street
Wilmington, North Carolina 28401
To get directions to this location, click "Directions" or "View larger map" on the map below (Google Maps will open in a new window).
View Map | Contact Us
Attorney Advertising. This website is designed for general information only. The information presented at this site should not be construed to be formal legal advice nor the formation of a lawyer/client relationship. [ Do Not Sell My Personal Information ] [ Site Map ] Martindale-Hubbell and martindale.com are registered trademarks; AV, BV, AV Preeminent and BV Distinguished are registered certification marks; Lawyers.com and the Martindale-Hubbell Peer Review Rated Icon are service marks; and Martindale-Hubbell Peer Review Ratings are trademarks of MH Sub I, LLC, used under license. Other products and services may be trademarks or registered trademarks of their respective companies. Copyright © 2021 MH Sub I, LLC. All rights reserved.


I'm deeply ashamed!!! Please forgive me, I didn't know what I were doing!!!
The devil made you do it. I'm sure.
RED, you are spot on!
Welll...., two Wilddogs are going on a girls-only quadbike safari in November. Want to go with?
to add insult to injury... Where's your helmet?
If you ride a quad you must behave like a hooligan so I left my helmet at my bike.
Looks more like a kwaad kat than kwatgatt.
Is that your 'I-am-not-'lus'-for-mud-to-jump-up-and-hit-me-in-the-face' facial expression ?
Only Windhoek light! love the beer, hate the "harde hout"
I'm acting the part of a quad rider, needs to work on my facial expression, think it's the look of confusion or I'm nearly in tears over missing my BIKE!!!


Not much to say here, other than, as bad as the condition of this matchbook is, the car still looks showroom new. Plus, I love the association to rockets. What is "Rocket Action" anyway? Does it burn up on re-entry to your garage? Were the matches sold with the car to *ahem* launch it? Maybe this was Oldsmobile's brief foray into external combustion engines.
Small specialized dealers like Lovells are quickly becoming a distant memory. Too bad, I bet you got really great service at Lovells Garage... and so many Oldsmobile models to choose from!
Perfect Exposure: Hoax or Coax?


text:
Home/Community News/Carpenter's Shelter New Heights Campaign Raises $2.2 Million, Exceeds Goal!
Community NewsGiving BackNonprofit News
Carpenter's Shelter New Heights Campaign Raises $2.2 Million, Exceeds Goal!
"We are on the verge of a new beginning," said Carpenter's Shelter Executive Director Shannon Steene.
Construction Rendering of the new development, looking south along Route 1. Carpenter's Shelter will occupy the first floor, and the apartment housing will occupy the top six. (Photo courtesy of AHDC)
Alexandria, VA – Carpenter's Shelter has done it! The nonprofit has exceeded its $2 million fundraising goal for its New Heights campaign, which will support its property redevelopment at its long-standing location.
Shannon Steene, Carpenter's Shelter's Executive Director, announced at a recent celebratory luncheon that the nonprofit raised $2,196,940.
"Some very late giving was such an amazing surprise. The community is clearly vested in our mission," Steene said. "We are on the verge of a new beginning. We will move into a building that is purpose-built and designed to be a shelter. Part of this campaign seeds our Innovation Fund, which is dedicated to exploring new approaches to become more effective and efficient in moving people from homeless to housed."
The New Heights Campaign, publicly launched in May 2019, supports Carpenter's Shelter's property redevelopment project at the shelter's long-standing location.
The Launch: Photos: Carpenter's Shelter Launches New Heights Campaign
With a recent $300,000 cash gift from Amazon, the New Heights campaign reached its fundraising goal ahead of schedule.
Don't Miss: Amazon Donates $300,000 to Finish Alexandria's New Carpenter's Shelter
Attendees included many of Carpenter's Shelters strongest advocates, from its Board of Directors and campaign leadership to corporate supporters such as Amazon's Director of U.S. Public Policy, Stephen Hartell.
Construction is projected to end the summer of 2020 with a 60-bed, purpose-built homeless shelter, 87 affordable apartments, and the 10 permanent supportive housing units.
Carpenter's Shelter also recognized the generous contributions from the Hoffman Family, LLC, John and Elizabeth Siegel, Daniel E. Offutt Charitable Trust, Earl W. Stafford and the additional donors in the successful completion of the New Heights Campaign.
Archive: Torpedo Factory Collaborates with Homeless Shelter to Install New Mural.
AMAZON Carpenter's Shelter new heights campaign
Be Careful: Holiday Decorating Can Be Dangerous
Mrs. Claus Needs Your Help With Holiday Gifts for Samuel L. Tucker Elementary School Families


Cook Islands 2017, 5$ Time Capsule, 1oz silver, square coin1oz / 31.1 g. 35 x 35 mm. Have a look at my other auctions! The item "Cook Islands 2017, 5$ Time Capsule, 1oz silver, square coin" is in sale since Thursday, June 01, 2017. This item is in the category "Coins & Paper Money\Coins\ World\Australia & Oceania\South Pacific". The seller is "www-space-coins-com" and is located in space-coins-com. This item can be shipped worldwide. Circulated/Uncirculated: Uncirculated Year: 2017 Composition: Silver Country/Region of Manufacture: Cook Islands Precious Metal Content: 1oz. Weight: 1oz.


Blue Sea v0.1 Freeware Download - Blue Sea will be a turn based mmorpg set in the underwater.
Pirated Software Hurts Software Developers. Using Blue Sea Free Download crack, warez, password, serial numbers, torrent, keygen, registration codes, key generators is illegal. We do not host any torrent files or links of Blue Sea from depositfiles.com, rapidshare.com, any file sharing sites.
Quazatron: RPG is going to be a 3D RPG with turn-based combats and story based on old ZX Spectrum game, Quazatron.
Critically acclaimed winner of the Pop Vox award for best mobile game is finally here.
The Heart of Crelos will be a side-scrolling rpg with turn-based combat. The graphical style will be modelled after 8-bit games, each object consisting of a base colour, a shadow colour and black, for outlining purposes. The game will have many secrets.


Reflections on God, faith and life. These are based on my Sunday sermons.
As we prepare for Christmas, we prepare for God - and that means putting ourselves into God's big story.
Roger the rectory dog shares his wisdom.
A reflection on Luke 13:1-9 in the light of the terrorist attacks on two mosques in Christchurch, New Zealand.
"Blessed are the poor": reflecting on my recent trip to Uganda with World Vision.
All content © 2019 Rev. Cathy. Interested in podcasting? Learn how you can start a podcast with Buzzsprout. Podcast hosting by Buzzsprout.


Finally, after a long time we managed to pay a visit to the star restaurant Kuppelrain in Kastelbell (South Tyrol). As hoped, it has met our expectations.
their small terrace which is overlooking the beautiful castle of Kastelbell.
6 course menu 90 € per person.
Lovingly designed plates and tasty dishes, we recommend this restaurant and, yes, we will come back, Mr. Trafoier, to visit you again!!!
Thumbs up for a creative traditional SouthTyrolean cuisine!


The Farm Advisory Service (FAS) is delivered under the Scottish Rural Development Programme and forms an important function in delivering Scottish Government (SG) action to support and develop agriculture in Scotland.
To implement the FAS, it is necessary to deliver targeted communications to farmers, crofters and land managers in Scotland, and to continue to communicate with customers who wish to know more about the service or to take advantage of the benefits. Some of this communication task is undertaken by SAC Consulting as a data processor under contract to the Scottish Government.
This processing is "necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller" – the tasks in question being the administration and management of CAP Schemes as defined in the various EU Regulations.


Sell your home with the Experts! The Mike Mulholland Team is your neighborhood expert. We go the extra mile to make sure our clients can meet their ultimate goals in the least amount of time with the least amount of inconvenience. Below is a list of Services we provide to our Seller's.
Work to get you the most money for your home in the shortest amount of time with the least amount of inconvenience to you.
Pre-approve buyers before showing your home and oversee all appointments for your property.
Negotiate the inspections and any other contingencies which are part of the agreement of sale that you accept, and attend closing as your representative.
If necessary, help you locate another property; locally, or anywhere in the world with the largest relocation network in the world.


text:
MAX HAVELAAR: OR, THE COFFEE AUCTIONS OF THE DUTCH TRADING COMPAN, a novel by Multatuli, reviewed by Dylan Cook
Cleaver Magazine Posted on August 8, 2019 by thwack June 20, 2020
MAX HAVELAAR: OR, THE COFFEE AUCTIONS OF THE DUTCH TRADING COMPANY
by Multatuli
translated by Ina Rilke and David McKay
New York Review Books, 336 pages
reviewed by Dylan Cook
Purchase this book to benefit Cleaver
Click here to purchase this book
"I call a man a fool if he dives in the water to rescue a dog from sharks." This is our introduction to Max Havelaar—a champion of the people, even irrationally so. He is a Dutchman who stands with Indonesian farmers. He is a bureaucrat who pushes against the orders of his superiors. Havelaar is a rare figure of compassion in the midst of Dutch imperialism, one who has the temerity and know-how to make tangible change. And, despite all of this, Max Havelaar is a minor character in the novel that bears his name.
Max Havelaar is likely an unfamiliar title to most American readers, and the Netherlands in general is an often overlooked source of literature. But make no mistake: the world over holds Max Havelaar in high regard. I recently had the chance to talk to a born-and-raised Dutchman, and I asked him if the title rang any bells. "Of course," he told me. "It's a classic, everyone reads it." Think along the lines of Pride and Prejudice. In his short but poignant introduction to this edition of the novel, Indonesian author Pramoedya Ananta Toer makes the bold claim that Max Havelaar is one of the most important novels of all time. There's a reason this novel caught the attention of writers like Karl Marx and Thomas Mann, and there's a reason that when Freud drew up a list of ten great authors, Multatuli stood on top.
Multatuli is the mononymous pen name of Eduard Douwes Dekker, the son of a Dutch sea captain. The name "Multatuli" stems of Latin and roughly translates to, "I have suffered greatly." When he was just eighteen, Dekker sailed on one of his father's ships to the Dutch East Indies where he worked in finance before shifting into a government position. After nearly twenty years there, he rose to become the Assistant Resident of Lebak, but, after disagreeing with the Dutch colonial system, soon resigned and returned to the Netherlands. A few years later, in 1860, he would publish a novel about a man who becomes the Assistant Resident of Lebak, only to become disgusted with Dutch imperialism.
Eduard Douwes Dekker, or Multatuli
Max Havelaar is a highly fragmented, nonlinear text. The novel features several narrators, depending on how you count, and the plot can quickly become cumbersome and difficult to follow. It begins with Batavius Drystubble, a coffee merchant in the Netherlands. He recounts the exact process of how this novel was written, all the while describing the highly political field of coffee brokering and how it requires the majority of his attention ("My business is my life" becomes something of a mantra for his narration). Along the way, Drystubble encounters an old acquaintance, Shawlman, who entrusts him with a packet of his writings, an eclectic mix of poetry and essays that Drystubble claims is the source material for the Max Havelaar portions of the novel. Of course, Drystubble is so engrossed in his work that he cannot possible spend his time writing, for his business is his life. Thus, he enlists Ludwig Stern, a friend of his son's, to write some of the chapters regarding Havelaar. Only then, a sizeable chuck into the text, does the story of Max Havelaar begin.
The two narrators are not shy and frequently speak directly do the reader to voice opinions and curate information. The source material from Shawlman lingers overhead, and Drystubble and Stern routinely reaffirm that they must cut out certain details that won't add anything to the novel. These metafictional moments make it feel more apt to group Multatuli along with early postmodern authors than with contemporaries like Hugo, Tolstoy, or Eliot. Multatuli constantly reminds us that he is writing a novel in the same way Italo Calvino reminds us that we are reading a novel. In the revised 1881 edition of the novel, Multatuli added an extensive network of endnotes, inserting everything from new details to personal opinions. He wanted the reader to know that the narrative is deeper than what exists on the page, and he did so in the same way that David Foster Wallace would in Infinite Jest more than a hundred years later.
You see, reader, I am searching for the answer to that how? Which is why my book is such a mixed bag. It's a book of samples: take your pick.
While Multatuli should be commended for his efforts to restructure narrative, one must consider the downside of taking such risks—there are unfortunately many times where he sacrifices clarity for creativity. The narrators provide so much of their own commentary that it is often difficult to get situated as the reader is torn between the Netherlands and the Dutch East Indies. The novel itself is so restless that the reader is never allowed to get immersed into a single narrative thread. To be frank, the style and structure of this novel read not quite unfinished, but a bit undercooked. For modern readers, there are many points where it may just seem easier to put down this book in favor of something a little more palatable. However, it is important to acknowledge that Multatuli wasn't trying to write something beautiful and easy to swallow. There is no room for poetics in Max Havelaar because Multatuli's goal was to inspire mutiny. The value in this novel is in what Multatuli says, not how he says it.
With that in mind, it's crucial to understand Max Havelaar within its historical context: Multatuli may not have written with beauty, but he certainly wrote with contempt. When this novel was first published in 1860, European imperialism was more than three centuries old. The vast majority of Africa, South Asia, and the Middle East were all under European rule. Any voices that challenged this system were usually mild enough to be suppressed. Max Havelaar is the rare exception. At every opportunity, Multatuli describes the faults of Dutch imperialism. Frequently, the novel digresses into essayish passages against the Dutch that are often more gripping than the surrounding narrative. Critiques are written with surgical precision, always attacking the Dutch and sparing Indonesians. There are no slurs or stereotypes in this novel. There is nothing that paints native Indonesians as anything "less." On the contrary, Multatuli treats the minutiae of Indonesian life with utmost respect to show his countrymen exactly how equal they are. Unlike Mark Twain, Multatuli was able to write about an oppressed group without including subtle linguistic cues that reinforce their marginalization.
Part of what makes Multatuli so adept as an exponent is his remarkable understanding of why. He does not settle for simply stating that oppression exists. Instead, he clearly explains how oppression is a systemic condition. Through Havelaar, we learn about the tactics of Dutch imperialism that perfected their hegemony. Dutch imperialists effectively made native Indonesians subjugate their compatriots. In the imperialist system, Dutch officials would appoint natives, called adipatis, to control smaller stretches of land. The Dutch would subsidize each adipati's lifestyle, making them rich. If an average farmer had any grievances, they would direct them towards the newly aristocratic adipati. The Dutch washed their hands of blame because their subjects likely never saw a Dutchman's face. Indonesians could never effectively rebel against the Dutch because they thought their problems were internal. The Dutch created a perfect system of exploitation, allowing them to create famines in Indonesia, home to some of the most fertile land on Earth. This is just one example of abuse. Multatuli gives us dozens.
Any turmoil that is impossible to conceal is blamed on a small gang of malefactors who will no longer cause any trouble now that overall contentment prevails. If want or famine has thinned the population, it was surely the result of crop failure, drought, rain, or something of the sort, and never of misgovernment.
Of course, any time the narrative begins to describe the atrocities taking place in Indonesia, Batavius Drystubble interjects. This is business after all, isn't it? And his business is his life (it's no coincidence that the capital of the Dutch East Indies was Batavia). If the Dutch do not maintain their control over Indonesia, then the coffee industry in the Netherlands will certainly collapse. For Drystubble, one of Max Havelaar's narrators, imperialism is necessary for economic survival. Any element of the novel that critiques the Dutch system is most assuredly written by Ludwig Stern. Max Havelaar, as magnanimous as he is, becomes less important as the two narrators vie for power over the message. Stern calls for change, while Drystubble calls for stasis. Multatuli highlights how the complacency in existing systems causes change to lag, even in the face of necessity. In the context of the novel, Max Havelaar is a past tense character. Despite the progress he personally made, he did little to affect the Dutch system that Drystubble and Stern live in in the present. Multatuli did not merely want to proselytize, he wanted to show that progress is a generational process.
At the end of WWII, European imperialism was vulnerable enough to be toppled, and Indonesia was one of the first nations in this new world liberate itself. In August 1945, before the Pacific War had fully ceased, Indonesia declared independence. Sukarno, Indonesia's first president, cited Max Havelaar as a personally influential text. Many Indonesians today agree, which is remarkable considering the novel wasn't translated into Indonesian until 1972. Indonesia was a model for a path to independence that other nations could follow, and within the next three decades most of Africa, South Asia, and the Middle East would be politically decolonized. Much of the world outside of the United States understands Max Havelaar's role in this domino effect. Reading this novel shows the absolute earliest stages of revolt in a way that's still resonant. This is the undeniable importance of this novel. Few novels have had such a profound effect on global politics, and that feat ought not to be ignored. Max Havelaar may not be the most leisurely read, but, at the very least, it's worth knowing the name.
◊◊
Dylan Cook is a student at the University of Pennsylvania where he studies English, with a concentration in creative writing, and Biology. He often reads and writes, and when he's not doing either of these things, he can be found working in a lab, lost in the woods somewhere, or at [email protected].
MAX HAVELAAR: OR, THE COFFEE AUCTIONS OF THE DUTCH TRADING COMPAN, a novel by Multatuli, reviewed by Dylan Cook Published on August 8, 2019 in fiction reviews, reviews, translation (Click for permalink.)


even the color I've managed to avoid the most...PINK!
officially become a pink lip convert! Who knew?
Disclosure: This post was sponsored by Refinery29 and all opinions are my own!
Effortlessly chic! I love those pants!!
Beautiful! This is one of your best looks.
I LOVE those trousers. So envious of them. haha.
Love your blog so much, maybe we could follow each other on Bloglovin and/or GFC, Facebook?
Love this look. Your booties are amazing.


The poster for UFC Fight Night: Silva vs. Bisping.
UFC Fight Night: Silva vs. Bisping (also known as UFC Fight Night 84) was a mixed martial arts event held on 27 February 2016 at The O2 Arena in London, England.
The event was the eighth that the promotion hosted in London and the fifth held at The O2 Arena.
Michael Bisping was originally expected to face Gegard Mousasi at this event in a non-headliner middleweight bout. However, on 24 December, Mousasi was replaced by former UFC Middleweight Champion Anderson Silva in favour of a main event. Three days later, it was announced that Mousasi would face former title challenger Thales Leites.
Jimi Manuwa was expected to face Nikita Krylov at this event. However, on 31 December, Manuwa pulled out of the bout due to an undisclosed injury and the fight was scrapped.
Henry Briones was expected to face Brad Pickett at the event. However, Briones pulled out of the bout on 22 January and was replaced by Francisco Rivera.
Łukasz Sajewski was expected to face Teemu Packalen at the event. However 16 February, Sajewski pulled out due to an injury and was replaced by promotional newcomer Thibault Gouti.
The event tied UFC 169 and UFC Fight Night: Machida vs. Mousasi for the most decisions at a single UFC event with 10.
^ Vera was deducted one point in round 3 for repeatedly grabbing the inside of Grant's glove.
^ Fight was stopped in the 3rd round after a groin strike rendered Danho unable to continue.
^ a b Staff (27 February 2016). "UFC Fight Night 84 draws announced attendance of 16,734 for $2 million gate". mmajunkie.com.
^ a b UFC Press Release (1 December 2015). "UFC returns to London". ufc.com. Retrieved 1 December 2015.
^ Marc Raimondi (24 December 2015). "Anderson Silva vs. Michael Bisping headlines London card on Fight Pass". mmafighting.com. Retrieved 24 December 2015.
^ Staff (27 December 2015). "Gegard Mousasi now meets Thales Leites at UFC Fight Night 83 in London". mmajunkie.com. Retrieved 27 December 2015.
^ Staff (31 December 2015). "Jimi Manuwa injured, out of UFC Fight Night 83 bout with Nikita Krylov". mmajunkie.com. Retrieved 31 December 2015.
^ Staff (22 January 2016). "Francisco Rivera in for Henry Briones to meet Brad Pickett at UFC Fight Night 83". mmajunkie.com. Retrieved 22 January 2016.
^ Staff (16 February 2016). "With Sajewski out, Teemu Packalen meets Thibault Gouti at UFC Fight Night 84 in London". mmajunkie.com. Retrieved 16 February 2016.
^ Mike Bohn (28 February 2016). "UFC Fight Night 84 post-fight facts: Bisping makes big splash in UFC record books". mmajunkie.com. Retrieved 5 March 2016.
^ "UFC Fight Night London". Ultimate Fighting Championship. Retrieved 1 December 2015.
^ "Photo: Michael Bisping-Anderson Silva scorecard surprisingly consistent for once". mmajunkie.com. 27 February 2016. Retrieved 28 February 2016.
^ Staff (27 February 2016). "UFC Fight Night 84 bonuses: You know that Bisping-Silva war got $50,000, right?". mmajunkie.com. Retrieved 27 February 2016.


text:
Adam Segal
Maurice R. Greenberg Senior Fellow for China Studies and Director, Digital and Cyberspace Policy Program, Council on Foreign Relations
Adam Segal is the Maurice R. Greenberg Senior Fellow for China Studies and director of the Digital and Cyberspace Policy Program at Council on Foreign Relations. He was previously an arms control analyst for the Union of Concerned Scientists' China Project. Segal has been a visiting scholar at the Hoover Institution at Stanford University, MIT's Center for International Studies, Shanghai Academy of Social Sciences, and Tsinghua University in Beijing. He has taught at Vassar College and Columbia University. Segal is the author of The Hacked World Order: How Nations Fight, Trade, Maneuver, and Manipulate in the Digital Age; Advantage: How American Innovation Can Overcome the Asian Challenge; and Digital Dragon.
How China's Crackdown Challenges the World
Power Shift: The New Borders and Boundaries of Our Digital World


Calling All Varmits Bert Popowski, 1952, black and white drawings, very good condition.
How To Train Your Bird Dog Horace Lytle, 1945, Hochwalt Co., back cover marked, other wise good condition.
House & Garden's second book of Interiors 1926, Richardson Wright, cover worn, oversized.
The Personality of the Cat Brandt Aymar, Bonanza Books, 1958, with dust jacket. "This book is for people who love cats and for cats who love people" Very good condition.
Cat People Bill Hayword, Dolphin Book, Doubleday & Co., Garden City New York, 1978, good condition.
Kindred of the Wild Charles G.D. Roberts, 1902, Colonial Press, many illustrations by Charles Livingston Bull, deckle edge, cover green with gilt, very good condition.
The Mineral Industry Richard Rothwell, 1925, Mc Graw Hill, 865 pages.
Wild Life on the Rockies Enos A. Mills, 1909, Houghton Miflin & Co., Beautiful cover with grizzly bear, eagle and snow covered Rockies.
The Life of the Bee Maurice Maeterlinck, 1919, Dodd Mead & Co., dust jacket small tears, other wise good condition.
Publisher: Dodd Mead & Co.
The Honey Bee A Manual of instruction in Apiculture Frank Benton, 1896, government printing, soft cover. Very good condition.
Illinois Plants Poisonus to Livestock 1946, L. R. Tehon, U of I, College of Agriculture S.C., very good condition.
Budgies As A New Pet Barry Martin, 1990, T.F.H. Publications, soft-cover. Cover creased. Very good condition.
The Ultimate Mushroom Book Complete Guide to Mushrooms-a Photographic A-Z of Types and 100 Original Recipes. Peter Jordan & Steven Wheeler, 1995, 256 pages, loads of color pictures, dust jacket, very good.
Cat-Lover's Anthology selected by Seon Manley and Gogo Lewis, 1979, Lothrop, Lee & Shepard, 20 Contemporary Stories of Family Cats, some authors are: Lilian Jackson Braun, Harriet Beecher Stowe, Thurber, Illustrated with numerous engravings some done by: Cruikshank, Seymour, Drake, Herford, Francis, Dolph, Birch. Dust jacket and book very good.
Walden Henry D. Thoreau, 1910, Thomas Y. Crowell, hardcover, good condition.
The Cat's Pajamas and Related Episodes 1st edition, 1967, 190 pages, hardcover with very good dust jacket.
Cats and All About Them Chapters on the breeds and how to recognize them, Breeding and Mating, The Kittens and their training, Feeding, Grooming, Registering & Showing, etc. There are 38 photographic illustrations of beautiful cats throughout 243 pages. Dust jacket light wear.
Silly About Cats Edited by Marbeth Reed, features "The Best Cat Cartoons from American and British Periodicals. Softcover, 96 pages, good condition.
The Cat Who Came for Christmas 240 pages, dust jacket and book very good.
The Cats of Punchbowl Farm Lots of photographs, book very good, dust jacket light wear, 124 pages, hardcover.
The Cat Who Blew the Whistle 240 Pages, hardcover book and dust jacket very good.


Welcome to Reflections Dental Laboratory, Inc!
Reflections Dental Laboratory is a full service laboratory in Lincoln, Nebraska. Since 1993 we have been providing dentists across the country with quality restorations at a truly remarkable price. Our staff has many years of experience in the industry, and are proud of the work we produce. If you have questions or concerns we are here to help.
Our goal is to get it right!


text:
Composer(s): Erwin Schulhoff
Artist(s): Caroline Weichert
"The labels attached to Schulhoff's music may read foxtrot, tango, shimmy or rag, but they translate for the ear into examples of sophisticated and artfully sculpted music. He had a rare talent for capturing the 1920s spirit of his time and turning it into something new that was persuasive through its simplicity, yet crafted with sufficient ingenuity to satisfy the intellect. This is what fuels my love affair with all of his music – the sonatas, miniatures and dances. The start of a new century seems exactly the right moment to document the achievements of one the 20th century's greatest composers!" — Caroline Weichert
SCHULHOFF, ERWIN (1894–1942)
Fünf Pittoresken • Sonata No. 2 • Zwei Klavierstücke • Musik für Klavier • Esquisses de Jazz
Caroline Weichert, piano
Czech composer Erwin Schulhoff assimilated the influence of Jazz with genuinely distinctive results. The Fünf Pittoresken absorb both Dada and Scott Joplin whilst more classicist influences, such as Ravel, suffuse the Second Piano Sonata. Esquisses de Jazz (1927) is perhaps his most outstanding Jazz-influenced piece – a perfect synthesis of dance rhythms, wit and irony.
5 Pittoresken, Op. 31 (1921) (00:18:10 )
No. 1. Foxtrott (00:02:38)
No. 2. Ragtime (00:02:59)
No. 3. In futurum (00:01:25)
No. 4. One-Step (00:02:13)
No. 5. Maxixe (00:04:10)
Piano Sonata No. 2 (1926) (00:15:56 )
I. Allegretto con moto (00:06:12)
II. Allegro giocoso (00:01:49)
III. Andante cantabile e rubato (00:04:16)
IV. Finale: Allegro moderato (00:03:50)
2 Studien (1936) (00:06:46 )
No. 1. Optimistische Komposition (00:03:20)
No. 2. Den tschechischen Arbeitern (00:03:41)
Musik für Klavier, Op. 35 (1920) (00:17:18 )
I. Vorspiel (00:01:56)
II. Thema mit variationen (00:09:49)
III. Vivo e giocoso (00:01:44)
IV. Nachspiel (00:03:59)
Esquisses de jazz (1927) (00:09:00 )
No. 1. Rag (00:02:16)
No. 2. Boston (00:03:33)
No. 3. Tango (00:01:36)
No. 4. Blues (00:01:29)
No. 5. Charleston (00:01:13)
No. 6. Black bottom (00:01:57)
Caroline Weichert was a pupil of Renate Kretschmar-Fischer at the Musikhochschule in Detmold, and also studied with Conrad Hansen, Vitaly Margulis and Yvonne Lefébure. A prizewinner at the Busoni, German Chopin and Schubert competitions, she has appeared regularly as a soloist with orchestras such as the Baden-Baden Philharmonie, Nordwestdeutsche Philharmonie and the Telekom-orchester. She received a Discobole award from the Académie du Disque Français for her recording début featuring works by Shostakovich. Weichert's first recording for Grand Piano, Schulhoff's Piano Works Volume 1, received wide critical acclaim, including the prestigious Choc de Classica and Pianiste magazine's Maestro awards.
Erwin Schulhoff was born in Prague on 8 June 1894 and showed musical ability from an early age. A musical career was decided upon on the recommendation of no less than Antonín Dvorák, and Schulhoff studied at the Prague Conservatory from 1904, followed by piano tuition in Vienna from 1906 then composition in Leipzig with Max Reger from 1908 and subsequently in Cologne with Fritz Steinbach from 1911. In the meantime he had laid the basis of a career as a pianist, while his efforts at composing were rewarded with the Mendelssohn Prize in 1918 for a piano sonata. His music up to the First World War had shown the expected influences from Brahms and Dvorák, and by way of Strauss, to Debussy and Scriabin, but four years in the Austrian army saw him adopt a more radical stance artistically and politically. In the next few years he absorbed the values of the Expressionism represented by Schoenberg and the Second Viennese School as well as the Dadaism espoused by Georg Grosz, whose advocacy of jazz was to find its way into much of Schulhoff's music from that period.
"With deft tenacity, humor, and grit, Caroline Weichert does her part to bring Erwin Schulhoff's piano works to life" – Ionarts
"Weichert's fine playing is heard in outstanding sound, and the notes add to our appreciation of this music." – American Record Guide
"This is a fascinating disc of music that is rarely heard and when as lovingly played as it is here deserves a wide listenership." – MusicWeb International
"Caroline Weichert is a magnificent pianist, and to hear Schulhoff played at this level is revelatory" — International Piano
"One can imagine all of those "piano gods" up in heaven looking down approvingly on Weichert and perhaps even persuaded that Schulhoff, indeed, had a thing or two to bring to the jazz party." — Examiner.com


Jon loves chatting & meeting people, signing photos, books & DVDs, telling tall tales from his experiences as the infamous trainstopping Deatheater & his acting career in general. He is also available to take part in panels, Q&A's or for MCing, hosting, & presenting your quiz, raffle or charity auction.
So if YOU have a convention or event be sure to book the one and only slow hand-raising servant of Voldemort.


text:
Gal Costa died: the moving video shared by the Brazilian singer hours before her death
November 10, 2022 by Jacob Smith
Brazilian singer Gal Costa passed away at the age of 77 – Credits: @Jordi Vidal
Sadness in the world of music. This Wednesday, November 9 Brazilian singer Gal Costa has died at the age of 77. His relatives confirmed the information to Or Balloon and the cause of death is still unknown. When the news of her was known, her fans quickly spoke about it on social networks and fired her. but she was a video with some emotional words that were published on the networks of the artist herself in the last hours which excited all his fans.
Gal Costa's last post, hours before her death (Photo: Twitter @GalCosta)
"My love, you bring me luck", can be read in the posting that was made from the singer's profile. "Gal Costa and Caetano Veloso sing 'Sorte', by Ronaldo Bastos and Celso Fonsecain Programa Chico e Caetano, in 1986″, continued the message. It was accompanied by a video in which both artists performed the song.
The material was the singer's last publication on the networks and was replicated both on her Twitter account and on Instagram, where in addition, he himself Caetano Veloso left the emoji of a heart as a comment.
Costa's death shocked the public in Brazil, as both she and her music became emblems that will leave an indelible mark on the culture. In recent months, she stayed away from the stage, as she had to focus on her health. In September had surgery to remove a lump in his right nasal cavity. He even canceled his participation at the Primavera Sound festival in São Paulo last weekend at the last minute. According to medical recommendations should be sheltered until the end of November.
Lula Da Silva's message after the death of Gal Costa
The death of the interpreter of "Um dia de domingo" shocked the world of music, but in particular the politics of Brazil. She was one of the artists who got involved and supported Lula da Silva in the last elections. For this reason, the president-elect expressed his sadness on the networks for the death of the artist.
Lula da Silva said goodbye to Gal Costa (Photo: Twitter @LulaOficial)
The politician shared a photo on his Twitter account of the two of them embracing and wrote: "Gal Costa was one of the greatest singers in the world, one of our main artists who took the name and songs of Brazil to the entire planet. His talent, his technique and his audacity enriched and renewed our culture, and marked the lives of millions of Brazilians". In turn, he maintained that today the country loses "one of its great voices" and expressed his condolences to his family, friends and admirers.
On the other hand, several art references and well-known figures in the media used social networks to say goodbye for the last time to one of the most recognized voices in Brazil.. "Very sad and shocked by the death of my sister Gaucha," said the artist Gilberto Gil.
Osvaldo Bazan fired the artist (Twitter Capture)
In turn, the journalist Osvaldo Bazán also expressed his sadness at the news: "Thank you for being so important in the music of my life, dear Gal Costa. I have 31 of your albums left to continue listening to always, always. Thank you thank you thank you".
Brazilian singer Gal Costa died this Wednesday at the age of 77 (Photo: Instagram @galcosta)
Meanwhile, Luis Bremer posted on Twitter: "An emblem of Brazilian music has passed away. A committed and full artist. Thank you for your art that will be eternal as your memory".
YOU MAY ALSO BE INTERESTED | ON VIDEO
Aaron Carter reconciled with his brother Nick before his death
We would love to give thanks to the author of this short article for this outstanding material
Categories Musicians Tags Brazilian, Costa, death, died, Gal, hours, moving, shared, singer, VIDEO
They release a preview of "The Whale": the prelude to Brendan Fraser's performance
Elon Musk sells Tesla shares worth 4 billion for Twitter


text:
HomeNews2017Paula Whyman receives 2017 TU Prize for Literature
Paula Whyman receives 2017 TU Prize for Literature
By Jan Lucas on August 13, 2017
Bethesda, Maryland, writer honored for 'honest and sharply observed' stories
Paula Whyman is the recipient of the 2017 Towson Prize for Literature for You May See a stranger, a collection of linked stories, (TriQuarterly Books/Northwestern University Press, 2016).
You May See a Stranger has garnered praise from many quarters, including a starred review in Publishers Weekly that hailed the book as "an honest and sharply observed linked story collection, spanning the life of Miranda Weber from her teens through her late 40s. ... Themes of love, sex, politics, and family run through the collection, and every detail has satisfying echoes later on. Together, these smart, artful stories capture a woman's life and the moments that define her."
Whyman's writing has appeared in McSweeney's Quarterly, Ploughshares, VQR, the Washington Post, and on NPR's All Things Considered.
She teaches in writers-in-schools programs through the Pen/Faulkner Foundation in Washington, D.C., and The Hudson Review in Harlem and the Bronx, New York.
Whyman received an MFA in literature and the Myra Sklarew Thesis Award from The American University. Her bio states that before going to graduate school, she was "a book editor with the American Psychological Association, as well as a bar-back, a meeting planner, an editor of cheesy real estate guides, a clerk in a custom T-shirt and gag emporium, and a camp counselor but not actually a Solid Gold dancer." It concludes: She has always been a writer."
Whyman lives in Bethesda, Maryland, where she is working on a novel.
Established in 1979 with a grant from Alice and Franklin Cooley, the Towson University Prize for Literature is awarded annually for a single book or book-length manuscript of fiction, poetry, drama or imaginative nonfiction by a Maryland writer. The prize is granted on the basis of literary and aesthetic excellence as determined by a panel of distinguished judges appointed by the university.


Investigators at the Massachusetts General Hospital (MGH) Cancer Center have identified a new genetic signature associated with bile duct cancer, a usually deadly tumor for which effective treatment currently is limited. Their report, which has been published online in The Oncologist, finds that growth-enhancing mutations in two related genes may account for nearly a quarter of bile duct tumors arising within the liver, presenting the possibility that drugs targeting this mutation could represent a new strategy to control tumor growth.
"Patients with bile duct cancer have a generally poor prognosis. Most of them are diagnosed with advanced or metastatic disease, so surgical resection is not feasible," says co-senior author Andrew Zhu, MD, PhD, director of Liver Cancer Research at the MGH Cancer Center. "Identifying this new and relatively common mutation in intrahepatic bile duct cancer may have significant implications for the diagnosis, prognosis and therapy of patients whose tumors harbor this mutation."
Cancers of the gallbladder and bile duct are diagnosed in 12,000 patients in the U.S. each year, the authors note; but only 10 percent are discovered early enough to allow successful surgical treatment. Chemotherapy is modestly effective, leading to an average survival time of less than one year.
The MGH Translational Research Laboratory was jointly established by the MGH Department of Pathology and the MGH Cancer Center to screen patient tumor samples for mutations known to drive tumor growth, identifying those that may be treatable with targeted therapies. As part of this project, the MGH team screened samples from 287 patients with gastrointestinal tumors for 130 known cancer-associated mutations and were surprised to find that 3 out of 12 biliary tract cancer tumors had mutations in a gene called IDH1. To confirm this finding, they ran a more detailed screen in additional samples, for a total of 62 bile duct tumors and 25 gallbladder tumors. Mutations in IDH1 were found in 13 percent of all bile duct tumors and in 23 percent of those located within the liver itself. Less commonly, mutations were identified in a similar gene IDH2.
"Mutations in these genes are rare examples of abnormalities that profoundly affect the normal function of a metabolic enzyme," says lead author Darrell Borger, PhD, co-director of the Translational Research Laboratory. "Our co-investigators previously found that, in other types of cancer, mutations in these genes cause overproduction and dramatic accumulation of the metabolite 2-hydroxyglutarate. How this causes tumor development is being actively investigated, and it is now emerging that 2-hydroxyglutarate can disrupt the activity of a family of proteins important in signal transduction and regulation of gene expression."
Although no approved drugs are currently available that target IDH mutations, extensive efforts are underway to develop such drugs, Zhu notes. "Identifying these mutations in bile duct cancer raises many questions, including whether mutational status can distinguish various types of bile duct tumors and help predict prognosis. Also of interest is determining whether high blood levels of 2-hydroxyglutarate could serve as a biomarker for IDH1/2 status, which could provide a minimally invasive way to monitor the effects of new IDH inhibitors that may become available," he says. Zhu is an associate professor, and Borger an instructor in Medicine at Harvard Medical School.
John Iafrate, MD, PhD, director of the Center for Integrated Diagnostics in MGH Pathology, is corresponding and co-senior author of the Oncologist paper. Additional co-authors are Kenneth Tanabe, MD, Kenneth Fan, Hector Lopez, Marek Ancukiewicz, PhD, Hannah Liebman, Eunice Kwak, MD, PhD, Jeffrey Clark, MD, David Ryan, MD, Vikram Deshpande, MBBS, Dora Dias-Santagata, PhD, and Leif Ellisen, MD, PhD, all of the MGH Cancer Center; Valeria Fantin, PhD, Kimberly Straley and David Schenkein, MD, Agios Pharmaceuticals; and Aram Hezel, MD, University of Rochester.


Talk about the having the best of both worlds! Enjoying a fireworks show while on the water is a wonderful way to combine two popular activities. There's just something about seeing the bright reflections on the water that makes you feel like you're getting twice as much enjoyment for your money. If you're like most people and have only experienced a fireworks show from dry land, you are in for a real treat. It's not only about the close proximity to the fireworks, but also the spectacular reflections of colorful bursts of fire on the water that make ordinary shore-side viewing second-rate to being on board one of our catamarans.
The Key West Rotary Club has been sponsoring this island city's annual Fourth of July fireworks display that lights up the sky and sparkles the water ever since President Gerald Ford presided over the nation's bicentennial celebration in Washington, D.C. (back in 1976). Although the pyrotechnics are launched from the end of the White Street Pier, you can avoid the crowds gathered on this tiny island (only 5.9 square miles) by enjoying this special event from the waters of the Atlantic Ocean. Veteran travelers to Key West and its native Conchs all know the advantages of viewing this 4th of July display from the water.
So remember, there's no need to fight the crowds for a seat (or a place to stand) to enjoy the fireworks in Key West, plus you can put away the mosquito spray. Cool Key West offers special cruises and they are the best way to see the fireworks, but don't wait any longer if you're thinking about booking seats. Our cruises offer unlimited appetizers, sodas, beer, wine and champagne. They fill up fast, and are always sold out in advance.
All of our special 4th of July fireworks cruises will return to shore at the conclusion of the fireworks. The fireworks begin about 9:00pm and generally last for 30 minutes or so.
As with all the activities we offer, here at CoolKeyWest.com we will make sure we find the right package just for you! Feel free to contact us at 1 800-814-COOL with any questions.


A master's degree offers students the chance to delve more deeply into specific areas of their chosen subject. Students participating in a master's program often have opportunities to interact with professionals who are experts in their field. Some programs are geared to students directly out of their undergraduate program while others are developed with professionals in mind.
What is a Master in Financial Law? If you are considering a career as a financial professional or if you are already employed and want to further your skills, this program could be a good match. Subjects of study may include finance law, private law, international trade, corporate finance, corporate governance and structured finance. Other topics may include document analysis and interpretation, financial theory, and behavioral finance. Classes may cover banking on an international level, in retail or investment settings, and central banking.
Students of this program enjoy many advantages, including the chance to work with expert instructors and talented professionals who are already established in the industry. Other benefits are found in the development of the skills most sought after by employers. These skills include document analysis and interpretation, familiarity with legal and regulatory literature, and writing techniques appropriate in this field.
Those individuals who are interested in participating in the program should contact schools individually to get tuition and fee schedules. These costs can vary from one school to another, especially as some educational institutions are located across international borders.
Graduates are well prepared for jobs in the financial industry, particularly those where in-depth knowledge and well-honed skills are required. The programs may result in a very specialized focus that prepares graduates to hold top-level jobs in investment banking, corporate financing, trade and investment firms, and international business.
Individuals who want to prepare for further success in the financial industry or hone an area of specialization can research their options in the program listing. After locating specific programs of interest, fill out the lead form. Search for your program below and contact directly the admission office of the school of your choice by filling in the lead form.


Stack tag bricks on top of each other to create blocks of code.
Easy-to-follow tutorials. Download the PDFs, then view on-screen or print out.
No complex typing, just drag-and-drop to make valid a HTML web page.
Created for all beginners. Great for kids from primary-school age, all the way up to adult.
Your browser remembers your work and lets you pick up where you left off. No need to remember to save.
Start making your first web page straight away; there's nothing to sign-up to and no log-in.


The federal government's «Energy Strategy 2050» jeopardizes the security of electricity supplies and the competitiveness of Switzerland's exporting industry. scienceindustries and Swissmem, as representatives of industries that are responsible for 73% of Swiss goods exports and whose 400,000 or so employees in Switzerland contribute over 14% to GDP, are therefore fundamentally opposed to the «Energy Strategy 2050».
The «Energy Strategy 2050» does not satisfactorily answer the question of how, against a backdrop of rising demand for electricity, it will be possible to compensate for the loss of nuclear power (40% of total electricity production) without jeopardizing security of supply. Switzerland will thus be confronted with the problem of being obliged to buy in large amounts of electricity from abroad, especially in winter. As things stand today, however, the necessary bilateral trade agreement has yet to be signed with the EU.
scienceindustries and Swissmem disagree with the further expansion of subsidies for renewable energies. Experience in Germany has shown that the large-scale, subsidy-driven promotion of stochastic power generation (in particular wind and solar generation) impairs security of supply and reduces the cost-efficiency of energy production. The politically motivated, centrally planned increases in the price of electricity and energy that Switzerland has unilaterally introduced will threaten the international competitiveness of its exporting industry. Even today, industrial electricity prices in Switzerland are already significantly higher than elsewhere in Europe. Adding further to the cost of electricity by increasing CO2 taxes and the 'feed-in remuneration at cost' (KEV) tariff is unacceptable given that the exporting industries already find themselves in a difficult situation.
The same is true of the intention to replace the current taxes on non-renewable energy sources with an incentive tax as of 2020. Any energy incentive tax introduced by Switzerland alone would result in huge increases in electricity and energy prices compared with other countries and thus greatly impair Switzerland's international competitiveness as a location for research and industry.
A legal ban on next-generation nuclear power stations – i.e. a technology that does not even exist yet – does not make any sense and is therefore not only unnecessary but wrong.
Moreover, it is imperative that the «Energy Strategy 2050» be legitimized by the Swiss people in a referendum.
scienceindustries and Swissmem are willing to agree to measures to increase energy efficiency if such measures are in line with the market. Incentive models and competitive tendering are a good fit with the strategic direction pursued by the companies in the industries for some years now. The industries further support the expansion of hydropower, the restructuring and extension of grid infrastructure and faster construction approval procedures for electricity generating stations and electricity grids.
Development of renewable energies in line with the market, i.e. no expansion of subsidies, but start-up financing for a limited period.