Total synthesis of Crotogossamide using an on-resin concomitant cyclization/cleavage reaction

Crotogossamide, a cyclic peptide isolated from the latex of Croton gossypifolius, has been synthesized by a rapid and efficient Boc solid-phase peptide synthesis. The strategy takes advantage of the oxime resin nucleophile susceptibility and comprises the synthesis of a linear precursor followed by on-resin head-to-tail concomitant cyclization/cleavage. In addition, we report the first antimicrobial and antibiofilm investigations on Crotogossamide

Crown ether helical peptides are preferentially inserted in lipid bilayers as a transmembrane ion channels

Oriented circular dichroism was used to study the alignment crown ether-modified peptides. The influence of different N- and C-functionalities was assessed using at variable peptide:lipid ratios from 1:20 to 1:200. Neither the functionalities nor the concentration had any major effect on the orientation. The alignment of the 21-mer peptides was also examined with lipid membranes of different bilayer thickness. The use of synchrotron radiation as light source allowed the study of peptide:lipid molar ratios from 1:20 to 1:1000. For all conditions studied, the peptides were found to be predominantly incorporated as a transmembrane helix into the membrane, especially at low peptide concentration, but started to aggregate on the membrane surface at higher peptide:lipid ratios. The structural information on the preferred trans-bilayer alignment of the crown ether functional groups explains their ion conductivity and is useful for the further development of membrane-active nanochemotherapeutics

UVUDF: Ultraviolet Imaging of the Hubble Ultradeep Field with Wide-field Camera 3

We present an overview of a 90-orbit Hubble Space Telescope treasury program to obtain near ultraviolet imaging of the Hubble Ultra Deep Field using the Wide Field Camera 3 UVIS detector with the F225W, F275W, and F336W filters. This survey is designed to: (i) Investigate the episode of peak star formation activity in galaxies at 1<z<2.5; (ii) Probe the evolution of massive galaxies by resolving sub-galactic units (clumps); (iii) Examine the escape fraction of ionizing radiation from galaxies at z~2-3; (iv) Greatly improve the reliability of photometric redshift estimates; and (v) Measure the star formation rate efficiency of neutral atomic-dominated hydrogen gas at z~1-3. In this overview paper, we describe the survey details and data reduction challenges, including both the necessity of specialized calibrations and the effects of charge transfer inefficiency. We provide a stark demonstration of the effects of charge transfer inefficiency on resultant data products, which when uncorrected, result in uncertain photometry, elongation of morphology in the readout direction, and loss of faint sources far from the readout. We agree with the STScI recommendation that future UVIS observations that require very sensitive measurements use the instrument's capability to add background light through a "post-flash". Preliminary results on number counts of UV-selected galaxies and morphology of galaxies at z~1 are presented. We find that the number density of UV dropouts at redshifts 1.7, 2.1, and 2.7 is largely consistent with the number predicted by published luminosity functions. We also confirm that the image mosaics have sufficient sensitivity and resolution to support the analysis of the evolution of star-forming clumps, reaching 28-29th magnitude depth at 5 sigma in a 0.2 arcsecond radius aperture depending on filter and observing epoch.Comment: Accepted A

Extended Cognition Hypothesis Applied to Computational Thinking in Computer Science Education

Computational thinking is a much-used concept in computer science education. Here we examine the concept from the viewpoint of the extended cognition hypothesis. The analysis reveals that the extent of the concept is limited by its strong historical roots in computer science and software engineering. According to the extended cognition hypothesis, there is no meaningful distinction between human cognitive functions and the technology. This standpoint promotes a broader interpretation of the human-technology interaction. Human cognitive processes spontaneously adapt available technology enhanced skills when technology is used in cognitively relevant levels and modalities. A new concept technology synchronized thinking is presented to denote this conclusion. More diverse and practical approach is suggested for the computer scienceeducation.Peer reviewe

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening "breakthrough" cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Attention! A good bedside test for delirium?

peer-reviewedBackground Routine delirium screening could improve delirium detection, but it remains unclear as to which screening tool is most suitable. We tested the diagnostic accuracy of the following screening methods (either individually or in combination) in the detection of delirium: MOTYB (months of the year backwards); SSF (Spatial Span Forwards); evidence of subjective or objective 'confusion'.Methods We performed a cross-sectional study of general hospital adult inpatients in a large tertiary referral hospital. Screening tests were performed by junior medical trainees. Subsequently, two independent formal delirium assessments were performed: first, the Confusion Assessment Method (CAM) followed by the Delirium Rating Scale-Revised 98 (DRS-R98). DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria were used to assign delirium diagnosis. Sensitivity and specificity ratios with 95% CIs were calculated for each screening method.Results 265 patients were included. The most precise screening method overall was achieved by simultaneously performing MOTYB and assessing for subjective/objective confusion (sensitivity 93.8%, 95% CI 82.8 to 98.6; specificity 84.7%, 95% CI 79.2 to 89.2). In older patients, MOTYB alone was most accurate, whereas in younger patients, a simultaneous combination of SSF (cutoff 4) with either MOTYB or assessment of subjective/objective confusion was best. In every case, addition of the CAM as a second-line screening step to improve specificity resulted in considerable loss in sensitivity.Conclusions Our results suggest that simple attention tests may be useful in delirium screening. MOTYB used alone was the most accurate screening test in older people.PUBLISHEDpeer-reviewe

General Education Learning Outcomes and Demographic Correlates in University Students in Hong Kong

Although there are studies showing that higher education would benefit university students, empirical research that comprehensively assesses student general education learning outcomes and related demographic correlates based on longitudinal data is minimal, especially in the Chinese context. To address the research gaps, the present study was conducted to investigate learning outcomes amongst university students in one university in Hong Kong based on a four-year longitudinal design (N = 460). Four dimensions of student general education learning outcomes were measured, including effective reasoning and problem solving, leadership, moral character, and integration of learning. Results suggested a U-shaped pattern of student learning outcomes for most dimensions, with no improvement or even a decrement in the second year and a steady growth thereafter. While family background did not affect student development, gender showed a significant moderating effect on students’ development in two dimensions (i.e., effective reasoning and problem solving, and integration of learning). These findings suggest that students benefit from general education-embedded university study in multiple dimensions, especially after the first year of transition period. Practical implications of the findings and future research directions were also discussed

Scientific drilling projects in ancient lakes: integrating geological and biological histories

Sedimentary sequences in ancient or long-lived lakes can reach several thousands of meters in thickness and often provide an unrivalled perspective of the lake's regional climatic, environmental, and biological history. Over the last few years, deep drilling projects in ancient lakes became increasingly multi- and interdisciplinary, as, among others, seismological, sedimentological, biogeochemical, climatic, environmental, paleontological, and evolutionary information can be obtained from sediment cores. However, these multi- and interdisciplinary projects pose several challenges. The scientists involved typically approach problems from different scientific perspectives and backgrounds, and setting up the program requires clear communication and the alignment of interests. One of the most challenging tasks, besides the actual drilling operation, is to link diverse datasets with varying resolution, data quality, and age uncertainties to answer interdisciplinary questions synthetically and coherently. These problems are especially relevant when secondary data, i.e., datasets obtained independently of the drilling operation, are incorporated in analyses. Nonetheless, the inclusion of secondary information, such as isotopic data from fossils found in outcrops or genetic data from extant species, may help to achieve synthetic answers. Recent technological and methodological advances in paleolimnology are likely to increase the possibilities of integrating secondary information, e.g., through molecular dating of molecular phylogenies. Some of the new approaches have started to revolutionize scientific drilling in ancient lakes, but at the same time, they also add a new layer of complexity to the generation and analysis of sediment core data. The enhanced opportunities presented by new scientific approaches to study the paleolimnological history of these lakes, therefore, come at the expense of higher logistic, communication, and analytical efforts. Here we review types of data that can be obtained in ancient lake drilling projects and the analytical approaches that can be applied to empirically and statistically link diverse datasets for creating an integrative perspective on geological and biological data. In doing so, we highlight strengths and potential weaknesses of new methods and analyses, and provide recommendations for future interdisciplinary deep drilling projects