On the structure of the Nx phase of symmetric dimers: inferences from NMR

NMR measurements on a selectively deuterated liquid crystal dimer CB-C9-CB, exhibiting two nematic phases, show that the molecules in the lower temperature nematic phase, NX, experience a chiral environment and are ordered about a uniformly oriented director throughout the macroscopic sample. The results are contrasted with previous interpretations that suggested a twist-bend spatial variation of the director. A structural picture is proposed wherein the molecules are packed into highly correlated chiral assemblies

Direito e tecnologia: a utilização de inteligências artificiais no processo decisório

TCC(graduação) - Universidade Federal de Santa Catarina. Centro de Ciências Jurídicas. Direito.O Poder Judiciário brasileiro enfrenta uma grave situação de crise. Essa crise se expressa pelo tempo de tramitação dos processos e pelo custo despendido pelo poder público na máquina judiciária anualmente. Grande parte das ações em trâmite pertence a uma pequena parcela de litigantes. Em razão desse contexto, muitas pessoas ficam desprovidas de acesso a uma justiça efetiva e de qualidade, a despeito de todas as garantias fundamentais a elas asseguradas na Constituição. O objetivo do presente trabalho é propor que a solução para os problemas estruturais da justiça brasileira se dá através da tecnologia, com a utilização de Inteligências Artificiais no processo decisório de casos com baixa complexidade, por meio do desenvolvimento de Sistemas de Apoio à Decisão. Para investigar o problema, utilizou-se o método de abordagem dedutivo, a partir da análise de dados estatísticos e pesquisa bibliográfica documental. Conclui-se que apesar do Poder Judiciário ter se estagnado na Revolução Industrial 3.0, a velocidade e amplitude que caracterizam as inovações atuais implicam na ruptura para uma Quarta Revolução Industrial. Nesse sentido, cabe ao Direito acompanhar e estudar as novas tecnologias para, com a devida cautela, promover a aplicação de Inteligências Artificias nos mais diversos campos da atividade jurídica, a fim de proporcionar uma prestação jurisdicional eficiente

Teaching clinicians shared decision making and risk communication online: an evaluation study

Objectives: To describe the development and initial evaluation of a brief e-learning course as a means of teaching shared decision making and risk communication skills to clinicians of all specialties. Design: Comparison pre-course and post-course of scores in subjective confidence and objective knowledge about shared decision making and risk communication. Setting: Online and open to all specialties and levels of clinical experience, including students. Participants: The course is freely available online and all who started the course from September 2018 to May 2020 were invited to participate in the evaluation study. Intervention: The self-guided e-learning course is made up of four modules and takes approximately 2 hours to complete. It is hosted on the website of the Winton Centre for Risk Communication and the UK’s National Health Service e-learning platform. Main outcome measures: Pre-course and post-course confidence in performing shared decision making (as measured by a 10-item scale adapted from the OPTION tool; total score range 10–50), and objective knowledge about basic principles of shared decision making and risk communication, as measured by performance on four knowledge questions and three calculations. At course commencement, a single item from the Berlin Numeracy Test, and the eight-item Subjective Numeracy Test were also asked. Results: Of 366 unique participants who consented and commenced the course, 210 completed all modules and the final post-course test. Participants’ mean age was 38.1 years, 69% were in current clinical practice and had a mean of 10.5 years of clinical practice. Numeracy was relatively low, with 50.7% correctly answering the Berlin Numeracy Test item pre-course. Participants who completed the course showed a significant improvement in their confidence by a mean summed score of 3.7 units (95% CI 2.9 to 4.6, p<0.0001) from a mean pre-course of 37.4 (SD 6.1) to post-course of 41.1 (SD 6.9). There was an increase in the proportion of correct answers for most knowledge questions (p<0.0001, p=0.013 for two directly compared), although no improvement in most skill questions that involved numbers (eg, calculating relative risks). Participants with higher numeracy appeared to show higher skill and confidence on most questions. Conclusions: This online, free e-learning course was successful in increasing participants’ confidence in, and some aspects of knowledge about, shared decision making and risk communication. It also highlighted the need for improvements in clinicians’ numerical skills as a vital part of training. We suggest that the course is used in combination with practical face-to-face experience and more intensive numerical skills training

The Repetitive Oligopeptide Sequences Modulate Cytopathic Potency but Are Not Crucial for Cellular Uptake of Clostridium difficile Toxin A

The pathogenicity of Clostridium difficile is primarily linked to secretion of the intracellular acting toxins A (TcdA) and B (TcdB) which monoglucosylate and thereby inactivate Rho GTPases of host cells. Although the molecular mode of action of TcdA and TcdB is well understood, far less is known about toxin binding and uptake. It is acknowledged that the C-terminally combined repetitive oligopeptides (CROPs) of the toxins function as receptor binding domain. The current study evaluates the role of the CROP domain with respect to functionality of TcdA and TcdB. Therefore, we generated truncated TcdA devoid of the CROPs (TcdA1–1874) and found that this mutant was still cytopathic. However, TcdA1–1874 possesses about 5 to 10-fold less potency towards 3T3 and HT29 cells compared to the full length toxin. Interestingly, CHO-C6 cells even showed almost identical susceptibility towards truncated and full length TcdA concerning Rac1 glucosylation or cell rounding, respectively. FACS and Western blot analyses elucidated these differences and revealed a correlation between CROP-binding to the cell surface and toxin potency. These findings refute the accepted opinion of solely CROP- mediated toxin internalization. Competition experiments demonstrated that presence neither of TcdA CROPs nor of full length TcdA reduced binding of truncated TcdA1–1874 to HT29 cells. We assume that toxin uptake might additionally occur through alternative receptor structures and/or other associated endocytotic pathways. The second assumption was substantiated by TER measurements showing that basolaterally applied TcdA1–1874 exhibits considerably higher cytotoxic potency than apically applied mutant or even full length TcdA, the latter being almost independent of the side of application. Thus, different routes for cellular uptake might enable the toxins to enter a broader repertoire of cell types leading to the observed multifarious pathogenesis of C. difficile

Influence of Substitutions in the Binding Motif of Proline-Rich Antimicrobial Peptide ARV-1502 on 70S Ribosome Binding and Antimicrobial Activity

Proline-rich antimicrobial peptides (PrAMPs) are promising candidates to treat bacterial infections. The designer peptide ARV-1502 exhibits strong antimicrobial effects against Enterobacteriaceae both in vitro and in vivo. Since the inhibitory effects of ARV-1502 reported for the 70 kDa heat-shock protein DnaK do not fully explain the antimicrobial activity of its 176 substituted analogs, we further studied their effect on the bacterial 70S ribosome of Escherichia coli, a known target of PrAMPs. ARV-1502 analogues, substituted in positions 3, 4, and 8 to 12 (underlined) of the binding motif D3KPRPYLPRP12 with aspartic acid, lysine, serine, phenylalanine or leucine, were tested in a competitive fluorescence polarization (FP) binding screening assay using 5(6)-carboxyfluoresceinlabeled (Cf-) ARV-1502 and the 70S ribosome isolated from E. coli BW25113. While their effect on ribosomal protein expression was studied for green fluorescent protein (GFP) in a cell-free expression system (in vitro translation), the importance of known PrAMP transporters SbmA and MdtM was investigated using E. coli BW25113 and the corresponding knockout mutants. The dissociation constant (Kd) of 201 16 nmol/L obtained for Cf-ARV-1502 suggests strong binding to the E. coli 70S ribosome. An inhibitory binding assay indicated that the binding site overlaps with those of other PrAMPs including Onc112 and pyrrhocoricin as well as the non-peptidic antibiotics erythromycin and chloramphenicol. All these drugs and drug candidates bind to the exit-tunnel of the 70S ribosome. Substitutions of the C-terminal fragment of the binding motif YLPRP reduced binding. At the same time, inhibition of GFP expression increased with net peptide charge. Interestingly, the MIC values of wild-type and DsbmA and DmdtM knockout mutants indicated that substitutions in the ribosomal binding motif altered also the bacterial uptake, which was generally improved by incorporation of hydrophobic residues. In conclusion, most substituted ARV-1502 analogs bound weaker to the 70S ribosome than ARV-1502 underlining the importance of the YLPRP binding motif. The weaker ribosomal binding correlated well with decreased antimicrobial activity in vitro. Substituted ARV-1502 analogs with a higher level of hydrophobicity or positive net charge improved the ribosome binding, inhibition of translation, and bacterial uptake