86,618 research outputs found

    Conceptual and Methodological Pitfalls in Experimental Studies: An Overview, and the Case of Alzheimer’s Disease

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    The main goal of scientific research is to uncover new knowledge to understand reality. In the field of life sciences, the aim of translational research—to transfer results “from bench to bedside”—has to contend with the problem that the knowledge acquired at the “bench” is often not reproducible at the “bedside,” raising the question whether scientific discoveries truly mirror the real world. As a result, researchers constantly struggle to overcome the dichotomy between methodological problems and expectations, as funding agencies and industries demand expandable and quick results whereas patients, who are uninterested in the epistemological dispute, only ask for an effective cure. Despite the numerous attempts made to address reproducibility and reliability issues, some essential pitfalls of scientific investigations are often overlooked. Here, we discuss some limitations of the conventional scientific method and how researcher cognitive bias and conceptual errors have the potential to steer an experimental study away from the search for the vera causa of a phenomenon. As an example, we focus on Alzheimer’s disease research and on some problems that may have undermined most of the clinical trials conducted to investigate it

    The carboxyl-terminal region is NOT essential for secreted and functional levels of coagulation factor X

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    Background: The homologous coagulation factor X (FX), VII (FVII), IX (FIX) and protein C (PC) display striking differences in the carboxyl-terminus, with that of FX being the most extended. This region is essential for FVII, FIX and PC secretion. Objectives: To provide experimental evidence for the role of the FX carboxyl-terminus. Methods: Recombinant FX (rFX) variants were expressed in multiple eukaryotic cell systems. Protein and activity levels were evaluated by ELISA, coagulant and amidolytic assays. Results and discussion: Expression of a panel of progressively truncated rFX variants in HEK293 cells revealed that the deletion of up to 21 residues in the carboxyl-terminus did not significantly affect secreted protein levels, as confirmed in HepG2 and BHK21 cells. In contrast, chimeric rFX-FVII variants with swapped terminal residues showed severely reduced levels. The truncated rFX variants revealed normal amidolytic activity, suggesting an intact active site. Intriguingly, these variants, which included that resembling the activated FXβ form once cleaved, also displayed remarkable or normal pro-coagulant capacity in PT- and aPTT-based assays. This supports the hypothesis that subjects with nonsense mutations in the FX carboxyl-terminus, so far never identified, would be asymptomatic. Conclusions: For the first time we demonstrate that the FX carboxyl-terminal region downstream of residue K467 is not essential for secretion and provides a modest contribution to pro-coagulant properties. These findings, which might suggest an involvement of the carboxyl-terminal region in the divergence of the homologous FX, FVII, FIX and PC, help to interpret the mutational pattern of FX deficiency

    Reactivity of vanadyl pyrophosphate catalyst in ethanol ammoxidation and β-picoline oxidation: Advantages and limitations of bi-functionality

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    This study investigates the catalytic activity of vanadyl pyrophosphate (VPP) for both gas-phase ethanol ammoxidation to acetonitrile and β-picoline oxidation to nicotinic acid. Both reactions may be alternative processes to the industrial technologies used to produce these two chemicals. The reaction networks were investigated, also by feeding possible intermediates; in-situ DRIFT spectroscopy was used to monitor the interaction of ethanol and ammonia with the catalyst. VPP bi-functionality features played an important role in the two reactions; specifically, acidity was detrimental either because it catalyzed undesired reactions, such as ethanol dehydration to ethylene during ethanol ammoxidation, or because it caused a strong interaction with reactants – especially those containing N atoms, ammonia and β-picoline – thus giving rise to some surface saturation phenomena which inhibited the consecutive reactions leading to the final desired compounds, acetonitrile and nicotinic acid. The co-feeding of steam helped product desorption, thus enhancing selectivity in β-picoline oxidation

    1-Butanol dehydration and oxidation over vanadium phosphate catalysts

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    The transformation of 1-butanol into either butenes or maleic anhydride was carried out both with and without oxygen, using V/P/O catalysts. With vanadyl pyrophosphate prepared by coprecipitation, at temperature lower than 240 ◦C and without oxygen, selectivity to butenes was higher than 90%, but a slow deactivation took place. At temperature higher than 300 ◦C and in the presence of air, maleic and phthalic anhydrides were the prevailing products, with selectivity of 60% and 14%, respectively. Catalytic performance was affected by crystallinity and acidity. αI-VOPO4 showed a poor performance in the absence of air, with a quick deactivation due to coke accumulation; but it displayed an excellent selectivity to butenes (close to 98%) at temperatures lower than 320 ◦C in the presence of air, with stable performance. At temperature higher than 360 ◦C, α I-VOPO4 was reduced to vanadyl pyrophosphate and catalyzed the direct oxidation of 1-butanol into maleic anhydride, but with 35% selectivit

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    [Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]

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    Newspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
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