Memoirs of the life of David Rittenhouse, LLD. F.R.S. : late president of the American philosophical society, &c. interspersed with various notices of many distinguished men: with an appendix, containing sundry philosophical and other papers, most of which have not hitherto been published.

Mode of access: Internet.

The Rittenhouse orrery : Princeton's eighteenth-century planetarium, 1767-1954 : a commentary on an exhibition held in the Princeton University Library /

Includes bibliographical references (p. 76-81).

Masarykův ideál moderního hrdiny : přednáška studentům v Nár. domě Vinohrad, dne 22.2 1920 /

Mode of access: Internet.

'A piece of fine meshwork': the intertwining fiction of Philip Roth and Edna O'Brien

This thesis comprises a comparative analysis of the works the Irish author Edna O’Brien and her contemporary and friend, the Jewish-American author Philip Roth. It investigates the striking biographical, textual and stylistic symmetries between two writers from very different cultures and literary traditions. The thesis begins with the, until now, undetected intertextual nexuses between Roth’s fiction and O’Brien’s. These allusions significantly alter the readings of a number of their novels, while at the same time indicating wider transatlantic frames of reference now apparent in their work. O’Brien has, since the beginning of her career, been in frequent correspondence with all of the pre-eminent Jewish-American authors of her time, and her work conducts a dialogue with key Jewish-American texts. Conversely, Roth’s fiction—like O’Brien’s, obviously indebted to Joyce—has frequently alluded to other seminal Irish authors. The literary and personal relationship of Roth and O’Brien symbolize myriad links between Jewish and Irish literary cultures. In O’Brien’s (and wider Irish) fiction, the Jew is often positioned as an exotic but dangerous “Other”. Equally, throughout the Jewish canon Irish Catholics are frequently employed as foils. Roth and O’Brien investigate difference by depicting relationships that cross these boundaries. Through understanding the complex interrelations at play between the fiction of Roth and O’Brien, and between their work and that of a wider pantheon of Irish and American writers, this thesis will reposition both as transnational authors while developing a culturally sensitive, textually nuanced account of their transatlantic literary relations.

Fine tuning for the tropics: application of eDNA technology for invasive fish detection in tropical freshwater ecosystems

Invasive species pose a major threat to aquatic ecosystems. Their impact can be particularly severe in tropical regions, like those in northern Australia, where >20 invasive fish species are recorded. In temperate regions, environmental DNA (eDNA) technology is gaining momentum as a tool to detect aquatic pests, but the technology's effectiveness has not been fully explored in tropical systems with their unique climatic challenges (i.e. high turbidity, temperatures and ultraviolet light). In this study, we modified conventional eDNA protocols for use in tropical environments using the invasive fish, Mozambique tilapia (Oreochromis mossambicus) as a detection model. We evaluated the effects of high water temperatures and fish density on the detection of tilapia eDNA, using filters with larger pores to facilitate filtration. Large-pore filters (20 μm) were effective in filtering turbid waters and retaining sufficient eDNA, whilst achieving filtration times of 2-3 min per 2-L sample. High water temperatures, often experienced in the tropics (23, 29, 35 °C), did not affect eDNA degradation rates, although high temperatures (35 °C) did significantly increase fish eDNA shedding rates. We established a minimum detection limit for tilapia (1 fish/0.4 megalitres/after 4 days) and found that low water flow (3.17 L/s) into ponds with high fish density (>16 fish/0.4 megalitres) did not affect eDNA detection. These results demonstrate that eDNA technology can be effectively used in tropical ecosystems to detect invasive fish species. © 2016 John Wiley & Sons Ltd.

Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1P29S) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1P29S showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

Identyfikacja blednych podpisow w kolekcjach

Weryfikacja poprawnosci podpisów cyfrowych jest obliczeniowo kosztowna. Aby ja zwiekszyc, zamiast pojedynczych podpisów weryfikacji poddaje sie kolekcje. Jezeli wszystkie podpisy w kolekcji sa poprawne, to cała kolekcja jest akceptowana. Pojawienie sie błednych podpisów w kolekcji powoduje, ze weryfikacja jest błedna. Nie mozna odrzucic całej kolekcji, zachodzi wiec koniecznosc identyfikacji błednych podpisów w kolekcji. W artykule zdefiniowano metody identyfikacji błednych podpisów. W szczególnosci okreslono weryfikacje typu „dziel i rzadz”, w których wejsciowe kolekcje sa dzielone na podkolekcje tak długo, az koncowe błedne kolekcje zawieraja pojedyncze podpisy. Opisano równiez weryfikator Hamminga identyfikujacy jeden błedny podpis w kolekcji oraz uogólniono ten weryfikator do postaci dwupoziomowego weryfikatora, umozliwiajacego identyfikacje dwóch błednych podpisów. Podano tez definicje ogólnego weryfikatora zdolnego do identyfikacji dowolnej liczby błednych podpisów w kolekcjach.

Antibodies against human herpesvirus 8 in black South African patients with cancer

Background Infection with human herpesvirus 8 (HHV-8) has been consistently linked to Kaposi's sarcoma, but its mode of transmission, association with other cancers, and interaction with the human immunodeficiency virus type 1 (HIV-1) are largely unknown. Methods Between January 1992 and December 1997, we interviewed 3591 black patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 in 3344 of the patients. Antibodies against HHV-8 were detected with an indirect immunofluorescence assay. The intensity of the fluorescent signal correlated well with the titers of antibodies (P<0.001). The relations among the presence of anti–HHV-8 antibodies, sociodemographic and behavioral factors, type of cancer, and the presence or absence of coexistent HIV-1 infection were examined with the use of unconditional logistic-regression models. Results Among the 3293 subjects with cancers other than Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 32 percent, which did not differ significantly from the standardized seroprevalence among black blood donors. Among these 3293 patients, the prevalence of antibodies against HHV-8 increased with increasing age (P<0.001) and an increasing number of sexual partners (P=0.05) and decreased with increasing years of education (P=0.007); it was not strongly associated with HIV-1 infection. Anti–HHV-8 antibodies were more frequent among black than white blood donors (P<0.001). Among the 51 patients with Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 83 percent, significantly higher than the prevalence among those without Kaposi's sarcoma (P<0.001). For 16 other specific types of cancer, including multiple myeloma (108 cases) and prostate cancer (202 cases), the variation in the standardized seroprevalence of antibodies against HHV-8 was not remarkable. At a given intensity of fluorescence of anti–HHV-8 antibodies, Kaposi's sarcoma was more frequent among HIV-1–positive patients than among those who were HIV-1–negative (P<0.001). Conclusions Among black patients with cancer in South Africa, the seroprevalence of anti–HHV-8 antibodies is high and is specifically associated with Kaposi's sarcoma, particularly at high titers.

Chronic lung infection by Pseudomonas aeruginosa biofilm is cured by L-Methionine in combination with antibiotic therapy

Bacterial biofilms are associated with 80-90% of infections. Within the biofilm, bacteria are refractile to antibiotics, requiring concentrations >1,000 times the minimum inhibitory concentration. Proteins, carbohydrates and DNA are the major components of biofilm matrix. Pseudomonas aeruginosa (PA) biofilms, which are majorly associated with chronic lung infection, contain extracellular DNA (eDNA) as a major component. Herein, we report for the first time that L-Methionine (L-Met) at 0.5 mu M inhibits Pseudomonas aeruginosa (PA) biofilm formation and disassembles established PA biofilm by inducing DNase expression. Four DNase genes (sbcB, endA, eddB and recJ) were highly up-regulated upon L-Met treatment along with increased DNase activity in the culture supernatant. Since eDNA plays a major role in establishing and maintaining the PA biofilm, DNase activity is effective in disrupting the biofilm. Upon treatment with L-Met, the otherwise recalcitrant PA biofilm now shows susceptibility to ciprofloxacin. This was reflected in vivo, in the murine chronic PA lung infection model. Mice treated with L-Met responded better to antibiotic treatment, leading to enhanced survival as compared to mice treated with ciprofloxacin alone. These results clearly demonstrate that L-Met can be used along with antibiotic as an effective therapeutic against chronic PA biofilm infection.

Comissão da Amazônia, Integração Nacional e de Desenvolvimento Regional da Câmara dos Deputados : uma análise das audiências públicas realizadas nas 53ª Legislatura

O instituto da Audiência Pública foi conferido às comissões permanentes do Congresso Nacional e está previsto no texto da Constituição Federal de 1988, no art. 58 §2º, II. Este trabalho tem o propósito de analisar as audiências públicas realizadas pela Comissão da Amazônia, Integração Nacional e de Desenvolvimento Regional (CAINDR) na 53ª Legislatura. Para tornar possível a pesquisa, elaborou-se um estudo de caso na CAINDR, órgão permanente da Câmara dos Deputados, para se averiguar como estão ocorrendo essas reuniões. Os resultados apurados mostraram que as audiências públicas realizadas pela CAINDR trataram dos mais diversos temas de interesse público e, em menor proporção, instruíram matérias em trâmite. Ao final da pesquisa, percebeu-se que existem variáveis impedindo que as audiências públicas atendam plenamente aos seus objetivos, que serão abordadas na análise dos dados e outras considerações, bem como na conclusão.

Terceirização na administração pública : conflitos na legislação, orçamentação e escrituração da despesa

Versa sobre a terceirização no setor público. Na seção inicial fornece-se uma visão panorâmica de contratação dessa natureza nas organizações tanto do setor privado, quanto do setor público. A seguir apresenta-se tópico sobre o arcabouço jurídico da terceirização na esfera pública. Na última seção relatam-se os conflitos existentes no tratamento desse instituto nas esferas conceitual-legal, orçamentária e de mérito. Nesse capítulo são abordados temas como, por exemplo: (a) o que é passível de terceirização – fornecimento de mão-de-obra ou prestação de serviços? Atividades-meio ou atividades-fim?; (b) utilização da contratação de mão-de-obra como forma de burlar as regras constitucionais do concurso público e o limite de pessoal; (c) abrangência da expressão “terceirização de mão-de-obra que se refere à substituição de servidores e empregados públicos”, contida no art. 18, § 1°, da Lei de Responsabilidade Fiscal (Lei Complementar n° 101, de 4 de maio de 2000), com ênfase na forma de escrituração e contabilização dos gastos com contratos de serviços de terceiros. Por fim, procede-se a uma análise de mérito sobre as vantagens e desvantagens da terceirização na Administração Pública.

Developmentally regulated transcription factors in Drosophila melanogaster

During early stages of Drosophila development the heat shock response cannot be induced. It is reasoned that the adverse effects on cell cycle and cell growth brought about by Hsp70 induction must outweigh the beneficial aspects of Hsp70 induction in the early embryo. Although the Drosophila heat shock transcription factor (dHSF) is abundant in the early embryo, it does not enter the nucleus in response to heat shock. In older embryos and in cultured cells the factor is localized within the nucleus in an apparent trimeric structure that binds DNA with high affinity. The domain responsible for nuclear localization upon stress resides between residues 390 and 420 of the dHSF. Using that domain as bait in a yeast two-hybrid system we now report the identification and cloning of a nuclear transport protein Drosophila karyopherin-α3(dKap- α3). Biochemical methods demonstrate that the dKap-α3 protein binds specifically to the dHSF's nuclear localization sequence (NLS). Furthermore, the dKap-α3 protein does not associate with NLSs that contain point mutations which are not transported in vivo. Nuclear docking studies also demonstrate specific nuclear targeting of the NLS substrate by dKap-α3.Consistant with previous studies demonstrating that early Drosophila embryos are refractory to heat shock as a result of dHSF nuclear exclusion, we demonstrate that the early embryo is deficient in dKap-α3 protein through cycle 12. From cycle 13 onward the transport factor is present and the dHSF is localized within the nucleus thus allowing the embryo to respond to heat shock.

The pair-rule gene fushi tarazu (ftz) is a well-studied zygotic segmentation gene that is necessary for the development of the even-numbered parasegments in Drosophila melanogastor. During early embryogenesis, ftz is expressed in a characteristic pattern of seven stripes, one in each of the even-numbered parasegments. With a view to understand how ftz is transcriptionally regulated, cDNAs that encode transcription factors that bind to the zebra element of the ftz promoter have been cloned. Chapter Ill reports the cloning and characterization of the eDNA encoding zeb-1 (zebra element binding protein), a novel steroid receptor-like molecule that specifically binds to a key regulatory element of the ftz promoter. In transient transfection assays employing Drosophila tissue culture cells, it has been shown that zeb-1 as well as a truncated zeb-1 polypeptide (zeb480) that lacks the putative ligand binding domain function as sequencespecific trans-activators of the ftz gene.

The Oct factors are members of the POU family of transcription factors that are shown to play important roles during development in mammals. Chapter IV reports the eDNA cloning and expression of a Drosophila Oct transcription factor. Whole mount in-situ hybridization experiments revealed that the spatial expression patterns of this gene during embryonic development have not yet been observed for any other gene. In early embryogenesis, its transcripts are transiently expressed as a wide uniform band from 20-40% of the egg length, very similar to that of gap genes. This pattern progressively resolves into a series of narrower stripes followed by expression in fourteen stripes. Subsequently, transcripts from this gene are expressed in the central nervous system and the brain. When expressed in the yeast Saccharomyces cerevisiae, this Drosophila factor functions as a strong, octamer-dependent activator of transcription. The data strongly suggest possible functions for the Oct factor in pattern formation in Drosophila that might transcend the boundaries of genetically defined segmentation genes.

Avaliação da exposição ao metil-mercúrio na população ribeirinha da baixada cuiabana, no Pantanal Mato-Grossense, Brasil

Os efeitos tóxicos do metil-mercúrio (MeHg) em seres humanos vêm sendo amplamente discutidos, a partir de episódios de contaminação devida a ingestão frequente de peixe contaminado, em Minamata, no Japão, ou ao consumo de pão preparado com cereais tratados com fungicidas a base de metil-mercúrio, no Iraque, indicando que o metil mercúrio pode afetar o sistema nervoso central. A população ribeirinha na região do Pantanal, Brasil, é dependente do peixe, como principal fonte de alimentos e proteínas. Naquela região, o resultado de décadas de mineração de ouro, em pequena escala, foi a contaminação de muitos sistemas aquáticos com mercúrio. Consequentemente, muitas espécies de peixes possuem níveis de MeHg relativamente altos. O objetivo deste trabalho foi avaliar o nível de exposição ao MeHg entre a população ribeirinha do Pantanal. No primeiro artigo, apresentam-se os resultados da validação do método recordatório de 24 horas auto-referido, utilizando-se, como padrão-ouro, o método da pesagem, tendo-se verificado que há aproximadamente um erro de 30% ao estimar a quantidade de peixe consumido por aquela população. Um erro deste pode ser importante em se tratando do consumo de peixes carnívoros, os quais apresentam altos teores de mercúrio. No segundo artigo, ao analisar a associação entre o status neurocognitivo e a concentração de mercúrio no cabelo da população acima, os resultados indicaram que adultos expostos ao metil-mercúrio, através do consumo de peixe, podem ter déficits importantes nas medidas do desempenho neurocomportamental, sem alterações detectáveis no humor ou afetividade. Os efeitos mais importantes do mercúrio, entre os indivíduos analisados, foram detectados nos testes de velocidade e destreza da coordenação motora fina, na inibição da resposta na busca visual, e em tarefas de atenção. No terceiro artigo, considerando-se as associações observadas na concentração de mercúrio no cabelo com alguns desfechos dos testes neuro-psicológicos aplicados, calculou-se a dose-marcadora (BMD) e o limite inferior do intervalo de confiança do BMD (BMDL). Os resultados da dose marcadora e da dose de referência provisória são concordantes com os resultados estimados pelas agências de saúde internacionais.