178 research outputs found

    Exploring the boundaries of vinylogous Mukaiyama aldol processes: stereoselective access to polyunsaturated homoallylic alcohols

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    Catalytic enantioselective vinylogous aldol reactions using extended enolates are of prominent value in synthetic organic chemistry. Here, we report our advances in the development of enantioselective bis-vinylogous and hyper-vinylogous Mukaiyama aldol reactions between a series of polyenylsilyloxy furans or polyenylsilyoxy indoles and aromatic aldehydes, realized by use of the enabling catalyst combination of silicon tetrachloride and Denmark’s chiral bis-phosphoramide base (R,R)-I. Several crucial issues such as the remote site-, enantio- and geometrical selectivity of the reaction will be highlighted, ultimately focusing on one main question: how far can we push the limits of the vinylogous reactivity transmittal?</i

    A Counterfactual Safety Margin Perspective on the Scoring of Autonomous Vehicles' Riskiness

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    Autonomous Vehicles (AVs) have the potential to provide numerous societal benefits, such as decreased road accidents and increased overall transportation efficiency. However, quantifying the risk associated with AVs is challenging due to the lack of historical data and the rapidly evolving technology. This paper presents a data-driven framework for comparing the risk of different AVs' behaviors in various operational design domains (ODDs), based on counterfactual simulations of "misbehaving" road users. We introduce the concept of counterfactual safety margin, which represents the minimum deviation from normal behavior that could lead to a collision. This concept helps to find the most critical scenarios but also to assess the frequency and severity of risk of AVs. We show that the proposed methodology is applicable even when the AV's behavioral policy is unknown -- through worst- and best-case analyses -- making the method useful also to external third-party risk assessors. Our experimental results demonstrate the correlation between the safety margin, the driving policy quality, and the ODD shedding light on the relative risk associated with different AV providers. This work contributes to AV safety assessment and aids in addressing legislative and insurance concerns surrounding this emerging technology

    acne ra 1 2 a novel uv selective face cream for patients with acne efficacy and tolerability results of a randomized placebo controlled clinical study

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    SummaryBackground General skincare measures such as the use of moisturisers and products containing adequate photoprotection are important components of acne patients' management to complement the pharmacological regimen. Acne RA-1,2 is a novel dermato-cosmetic product which contains selective photofilters and active ingredients against the multifactorial pathophysiology of acne. Objectives To evaluate the tolerability of Acne RA-1,2 and its effect on the clinical signs of acne. Methods This double-blind, placebo-controlled study randomized 40 adult patients with 10-25 comedones per half face to once-daily application of Acne RA-1,2 or placebo for 8 weeks. Evaluations after 4 and 8 weeks included the number of comedones, transepidermal water loss (TEWL), sebum production, and tolerability. Results In the Acne RA-1,2 group, there was a significant 35% decrease in the mean number of comedones from 26 at baseline to 17 at Week 8 (P<.001), a 7% significant reduction in TEWL (9.32 to 8.66 g/h/m2; P<.001), and a 24% significant reduction in sebum production (154.8 to 117.6 Îźg/cm2; P<.001). The reductions in TEWL and sebum production were significantly greater than those in the placebo group at Weeks 4 and 8 (P<0.05). There were no adverse events. Conclusions Acne RA-1,2 was well tolerated and effective at reducing comedones and sebum production and improving epidermal barrier function. These results suggest that Acne RA-1,2 is useful against acne-prone facial skin, particularly as it targets sebum production, which topical pharmacological acne therapies do not address

    miniaturized fish for screening of onco hematological malignancies

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    Fluorescence in situ hybridization (FISH) represents a major step in the analysis of chromosomal aberrations in cancer. It allows the precise detection of specific rearrangements, both for diagnost..

    Pirin delocalization in melanoma progression identified by high content immuno-detection based approaches

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    <p>Abstract</p> <p>Background</p> <p>Pirin (PIR) is a highly conserved nuclear protein originally isolated as an interactor of NFI/CTF1 transcription/replication factor. It is a member of the functionally diverse cupin superfamily and its activity has been linked to different biological and molecular processes, such as regulation of transcription, apoptosis, stress response and enzymatic processes. Although its precise role in these functions has not yet been defined, PIR expression is known to be deregulated in several human malignancies.</p> <p>Results</p> <p>We performed immunohistochemical analysis of PIR expression in primary samples from normal human tissues and tumors and identified a dislocation of PIR to the cytoplasm in a subset of melanomas, and a positive correlation between cytoplasmic PIR levels and melanoma progression. PIR localization was subsequently analyzed <it>in vitro </it>in melanoma cell lines through a high content immunofluorescence based approach (ImmunoCell-Array).</p> <p>Conclusions</p> <p>The high consistency between <it>in vivo </it>and <it>in vitro </it>results obtained by immunohistochemistry and ImmunoCell-Array provides a validation of the potential of ImmunoCell-Array technology for the rapid screening of putative biological markers, and suggests that cytoplasmic localization of PIR may represent a characteristic of melanoma progression.</p

    Systematic study of the correlation between surface chemistry, conductivity and electrocatalytic properties of graphene oxide nanosheets

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    A main advantage of graphene oxide (GO) over other materials is the high tunability of its surface functional groups and of its electric conductivity. However, the complex chemical composition of GO renders difficult to unravel the correlation between structural and electric properties. Here, we use a combination of electron spectroscopy and electrochemistry to correlate the surface chemistry of GO to its electrical conductivity and electrocatalytic properties with respect to two molecules of high biological interest: β-nicotinamide adenine dinucleotide (NADH) and vitamin C. We demonstrate that the electrocatalytic properties of the material are due to hydroxyl, carbonyl and carboxyl groups residues that, even if already present on pristine GO, become electroactive only upon GO reduction. The results of this study demonstrate the advantages in the use of GO in amperometric biosensing and in enzymatic biofuel cells: it allows the oxidation of the target molecules at low potential values, with a sensitivity &gt;15 times higher with respect to standard, carbon-based electrode materials. Finally, we demonstrate that the right amount of chemical groups to achieve such high performance can be obtained also by direct electrochemical exfoliation of bulk graphite, without passing through GO production, thus rendering this approach suitable for cheap, large-scale applications

    Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross‐Cycloadditions: DFT‐Supported Homo‐Synergistic Organocatalytic Approach

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    The discovery of chemical methods enabling the construction of carbocycle‐fused uracils which embody a three‐dimensional and functional‐group‐rich architecture is a useful tool in medicinal chemistry oriented synthesis. In this work, an unprecedented amine‐catalyzed [4+2] cross‐cycloaddition is documented; it involves remotely enolizable 6‐methyluracil‐5‐carbaldehydes and β‐aryl enals, and chemoselectively produces two novel bicyclic and tricyclic fused uracil chemotypes in good yields with a maximum level of enantiocontrol. In‐depth mechanistic investigations and control experiments support an intriguing homo‐synergistic organocatalytic approach, where the same amine organocatalyst concomitantly engages both aldehyde partners in a stepwise eliminative [4+2] cycloaddition, whose vinylogous iminium ion intermediate product may diverge—depending upon conditions—to either bicyclic targets by hydrolysis or tricyclic products by a second homo‐synergistic trienamine‐mediated stepwise [4+2] cycloaddition

    Nintedanib-Containing Dual Conjugates Targeting ιVβ6 Integrin and Tyrosine Kinase Receptors as Potential Antifibrotic Agents

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    ιVβ6 Integrin plays a fundamental role in the activation of transforming growth factor-β (TGF-β), the major profibrotic mediator; for this reason, ιVβ6 ligands have recently been forwarded to clinical phases for the therapy of fibrotic diseases. Herein, we report the synthesis and in vitro biological evaluation as antifibrotic agents of three new covalent conjugates, constituted by c(AmpLRGDL), an ιVβ6 integrin-recognizing small cyclopeptide, and nintedanib, a tyrosine kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF) treatment. One of these conjugates recapitulates optimal in vitro antifibrotic properties of the two active units. The integrin ligand portion within the conjugate plays a role in inhibiting profibrotic stimuli, potentiating the nintedanib effect and favoring the selective uptake of the conjugate in cells overexpressing ιVβ6 integrin. These results may open a new perspective on the development of dual conjugates in the targeted therapy of IPF

    Correction: Wound healing properties of hyaluronan derivatives bearing ferulate residues

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    Correction for 'Wound healing properties of hyaluronan derivatives bearing ferulate residues' by Giuseppe Valacchi et al., J. Mater. Chem. B, 2015, DOI: 10.1039/c5tb00661a

    Search strings for the study of putative occupational determinants of disease

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    Objective To identify efficient PubMed search strategies to retrieve articles regarding putative occupational determinants of conditions not generally considered to be work related. Methods Based on MeSH definitions and expert knowledge, we selected as candidate search terms the four MeSH terms describing 'occupational disease', 'occupational exposure', 'occupational health' and 'occupational medicine' (DEHM) alongside 22 other promising terms. We first explored overlaps between the candidate terms in PubMed. Using random samples of abstracts retrieved by each term, we estimated the proportions of articles containing potentially pertinent information regarding occupational aetiology in order to formulate two search strategies (one more 'specific', one more 'sensitive'). We applied these strategies to retrieve information on the possible occupational aetiology of meningioma, pancreatitis and atrial fibrillation. Results Only 20.3% of abstracts were retrieved by more than one DEHM term. The more 'specific' search string was based on the combination of terms that yielded the highest proportion (40%) of potentially pertinent abstracts. The more 'sensitive' string was based on the use of broader search fields and additional coverage provided by other search terms under study. Using the specific string, the numbers of abstracts needed to read to find one potentially pertinent article were 1.2 for meningioma, 1.9 for pancreatitis and 1.8 for atrial fibrillation. Using the sensitive strategy, the numbers needed to read were 4.4 for meningioma, 8.9 for pancreatitis and 10.5 for atrial fibrillation. Conclusions The proposed strings could help health care professionals explore putative occupational aetiology for diseases that are not generally thought to be work relate
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