122,021 research outputs found
Mark S. Micale, Approaching Hysteria : Disease and its Interpretations
No full textCoffin Jean-Christophe. Mark S. Micale, Approaching Hysteria : Disease and its Interpretations. In: Annales. Histoire, Sciences Sociales. 53ᵉ année, N. 2, 1998. pp. 326-327
Peptidyl Fluoromethyl Ketones and Their Applications in Medicinal Chemistry
No full textPeptidyl fluoromethyl ketones occupy a pivotal role in the current scenario of synthetic chemistry, thanks to their numerous applications as inhibitors of hydrolytic enzymes. The insertion of one or more fluorine atoms adjacent to a C-terminal ketone moiety greatly modifies the physicochemical properties of the overall substrate, especially by increasing the reactivity of this functionalized carbonyl group toward nucleophiles. The main application of these peptidyl α-fluorinated ketones in medicinal chemistry relies in their ability to strongly and selectively inhibit serine and cysteine proteases. These compounds can be used as probes to study the proteolytic activity of the aforementioned proteases and to elucidate their role in the insurgence and progress on several diseases. Likewise, if the fluorinated methyl ketone moiety is suitably connected to a peptidic backbone, it may confer to the resulting structure an excellent substrate peculiarity and the possibility of being recognized by a specific subclass of human or pathogenic proteases. Therefore, peptidyl fluoromethyl ketones are also currently highly exploited for the target-based design of compounds for the treatment of topical diseases such as various types of cancer and viral infections
Mark S. Micale, Approaching Hysteria : Disease and its Interpretations
No full textCoffin Jean-Christophe. Mark S. Micale, Approaching Hysteria : Disease and its Interpretations. In: Annales. Histoire, Sciences Sociales. 53ᵉ année, N. 2, 1998. pp. 326-327
Synthesis and anti-HIV activity evaluation of new phenyl ethyl thiourea (PET) derivatives
No full textThis manuscript describes the synthesis of a new series of phenyl ethyl thiourea (PET) derivatives, with the aim to extend the SAR studies of the well known PET molecules endowed with anti-HIV activity. Preliminary results indicated that the synthesized compounds possess low anti-HIV activity
Direct and Chemoselective Synthesis of Tertiary Difluoroketones via Weinreb Amide Homologation with a CHF2-Carbene Equivalent
No full textThe homologation of Weinreb amides into difluoromethylketones with a formal nucleophilic CHF2 transfer agent is reported. Activating TMSCHF2 with potassium tert-amylate enables a convenient access to the difluorinated homologation reagent, which adds to the acylating partners. The high chemoselectivity showcased in the presence of variously multifunctionalized Weinreb amides, jointly with uniformly high yields, enables the strategy of general applicability without requiring any stabilization element for the putative carbanion
Influence of thermal buoyancy on heat transfer in spacer-filled channels for Membrane Distillation
No full textNumerical results are discussed for the flow in a horizontal plane channel filled with a novel sphere-rod spacer and exchanging heat from both the top and the bottom sides. Direct Numerical Simulations (DNS) are compared with RANS ones based on different turbulence models in the Reynolds number range 100~2000. Preliminary comparisons for non-buoyant flow show that models using wall functions perform poorly, grossly overpredicting Nusselt numbers, while ω-based models resolving the viscous-conductive sublayer all yield satisfactory results. In the presence of buoyancy, simulations using either DNS or the k-ω model yield a thermal asymmetry between top and bottom wall, confirmed by experiments and related to the stable or unstable thermal stratification occurring in the lower and upper layers of the channel. The asymmetry, large at low Re, becomes negligible for Re≥1000. The Spalart-Allmaras model yields satisfactory results in the absence of buoyancy but grossly overpredicts Nu in buoyant flows
SARS-CoV-2 Mpro: A potential target for peptidomimetics and small-molecule inhibitors
No full textThe uncontrolled spread of the COVID-19 pandemic caused by the new coronavirus SARS-CoV-2 during 2020–2021 is one of the most devastating events in the history, with remarkable impacts on the health, economic systems, and habits of the entire world population. While some effective vaccines are nowadays approved and extensively administered, the long-term efficacy and safety of this line of intervention is constantly under debate as coronaviruses rapidly mutate and several SARS-CoV-2 variants have been already identified worldwide. Then, the WHO’s main rec-ommendations to prevent severe clinical complications by COVID-19 are still essentially based on social distancing and limitation of human interactions, therefore the identification of new target-based drugs became a priority. Several strategies have been proposed to counteract such viral in-fection, including the repurposing of FDA already approved for the treatment of HIV, HCV, and EBOLA, inter alia. Among the evaluated compounds, inhibitors of the main protease of the corona-virus (Mpro) are becoming more and more promising candidates. Mpro holds a pivotal role during the onset of the infection and its function is intimately related with the beginning of viral replication. The interruption of its catalytic activity could represent a relevant strategy for the development of anti-coronavirus drugs. SARS-CoV-2 Mpro is a peculiar cysteine protease of the coronavirus family, responsible for the replication and infectivity of the parasite. This review offers a detailed analysis of the repurposed drugs and the newly synthesized molecules developed to date for the treatment of COVID-19 which share the common feature of targeting SARS-CoV-2 Mpro, as well as a brief overview of the main enzymatic and cell-based assays to efficaciously screen such compounds
Straight fiber bundles with non-uniform porosity: Shell-side hydrodynamics and mass transfer in cross flow
No full textThis study explores fully developed shell-side hydrodynamics and mass transfer past straight fiber bundles with non-uniform porosity in cross-flow. Simplified geometries made up by checkerboard arrays of alternately high and low porosity regions are considered. Simulations are performed for two domain sizes: a small geometry (26 fibers) and a large geometry (104 fibers). In the small geometry, the Darcy friction coefficient (fT) exhibits hydraulic isotropy at low transverse flow Reynolds numbers (ReT) but becomes dependent on the flow attack angle (θ) at higher ReT. In the large geometry, this dependency is observed at lower ReT. A non-uniform porosity reduces fT at almost all ReT and θ in the small geometry, with the large geometry exhibiting a more complex behavior. Regarding mass transfer, up to ReT≈1-10 (depending on θ), a non-uniform porosity leads to lower Sherwood numbers compared to regular square arrays. However, at higher ReT, it enhances mass transfer
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