Explore the vast range of titles available.

Solid-phase peptide synthesis (SPPS) is the preferred strategy for synthesizing most peptides for research purposes and on a multi-kilogram scale. One key to the success of SPPS is the continual evolution and improvement of the original method proposed by Merrifield. Over the years, this approach has been enhanced with the introduction of new solid supports, protecting groups for amino acids, coupling reagents, and other tools. One of these improvements is the use of the so-called “safety-catch” linkers/resins. The linker is understood as the moiety that links the peptide to the solid support and protects the C-terminal carboxylic group. The “safety-catch” concept relies on linkers that are totally stable under the conditions needed for both α-amino and side-chain deprotection that, at the end of synthesis, can be made labile to one of those conditions by a simple chemical reaction (e.g., an alkylation). This unique characteristic enables the simultaneous use of two primary protecting strategies: tert-butoxycarbonyl (Boc) and fluorenylmethoxycarbonyl (Fmoc). Ultimately, at the end of synthesis, either acids (which are incompatible with Boc) or bases (which are incompatible with Fmoc) can be employed to cleave the peptide from the resin. This review focuses on the most significant “safety-catch” linkers.

One proposed function of imagery is to make thoughts more emotionally evocative through sensory simulation, which can be helpful both in planning for future events and in remembering the past, but also a hindrance when thoughts become overwhelming and maladaptive, such as in anxiety disorders. Here, we report a novel test of this theory using a special population with no visual imagery: aphantasia. After using multi-method verification of aphantasia, we show that this condition, but not the general population, is associated with a flat-line physiological response (skin conductance levels) to reading and imagining frightening stories. Importantly, we show in a second experiment that this difference in physiological responses to fear-inducing stimuli is not found when perceptually viewing fearful images. These data demonstrate that the aphantasic individuals' lack of a physiological response when imaging scenarios is likely to be driven by their inability to visualize and is not due to a general emotional or physiological dampening. This work provides evidence that a lack of visual imagery results in a dampened emotional response when reading fearful scenarios, providing evidence for the emotional amplification theory of visual imagery.

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine that plays an important role in the pathogenesis of autoimmune diseases. The aim of the study was to establish an association between TNF-α promoter variability and systemic sclerosis (SSc). The study included 43 SSc patients and 74 controls. Four single nucleotide polymorphisms (rs361525, rs1800629, rs1799724, and rs1799964) located at the promoter of the TNFA gene were genotyped using commercially available TaqMan allelic discrimination assays with real-time PCR. The rs1799724 allele was associated with an increased SSc susceptibility (p = 0.028). In turn, none of the polymorphisms studied were related to the clinical and laboratory parameters of SSc patients, except for a higher prevalence of anti-Ro52 antibodies in the AG rs1800629 genotype in comparison to GG carriers (p = 0.04). Three of four cancer patients had both CT rs1799964 and AG rs361525 genotypes; thus, both of them were related to the increased risk of cancer, as compared to the TT (p = 0.03) and GG carriers (p = 0.0003), respectively. The TNFA C rs1799724 variant is associated with an increased risk of SSc, while the CT rs1799964 and AG rs361525 genotypes might enhance cancer susceptibility in SSc patients, although large observational and experimental studies are needed to verify the above hypothesis.

Hyperspectral LiDAR (HSL) technology can obtain spectral and ranging information from targets by processing the recorded waveforms and measuring the time of flight (ToF). With the development of the supercontinuum laser (SCL), it is technically easier to develop an active hyperspectral LiDAR system that can simultaneously collect both spatial information and extensive spectral information from targets. Compared with traditional LiDAR technology, which can only obtain range and intensity information at the selected spectral wavelengths, HSL detection technology has demonstrated its potential and adaptability for various quantitative applications from its spectrally resolved waveforms. However, with most previous HSLs, the collected spectral information is discrete, and such information might be insufficient and restrict the further applicability of the HSLs. In this paper, a tunable HSL technology using an acousto-optic tunable filter (AOTF) as a spectroscopic device was proposed, designed, and tested to address this issue. Both the general range precision and the accuracy of the spectral measurement were evaluated. By tuning the spectroscopic device in the time dimension, the proposed AOTF-HSL could achieve backscattered echo with continuous coverage of the full spectrum of 500–1000 nm, which had the unique characteristics of a continuous spectrum in the visible and near infrared (VNIR) regions with 10 nm spectral resolution. Yellow and green leaves from four plants (aloe, dracaena, balata, and radermachera) were measured using the AOTF-HSL to assess its feasibility in agriculture application. The spectral profiles measured by a standard spectrometer (SVC© HR-1024) were used as a reference for evaluating the measurements of the AOTF-HSL. The difference between the spectral measurements collected from active and passive instruments was minor. The comparison results show that the AOTF-based consecutive and high spectral resolution HSL was effective for this application.

The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to substrate specificity screening of TMPRSS2, we have discovered covalent small-molecule ketobenzothiazole (kbt) TMPRSS2 inhibitors which are structurally distinct from and have significantly improved activity over the existing known inhibitors Camostat and Nafamostat. Lead compound MM3122 (4) has an IC50 (half-maximal inhibitory concentration) of 340 pM against recombinant full-length TMPRSS2 protein, an EC50 (half-maximal effective concentration) of 430 pM in blocking host cell entry into Calu-3 human lung epithelial cells of a newly developed VSV-SARS-CoV-2 chimeric virus, and an EC50 of 74 nM in inhibiting cytopathic effects induced by SARS-CoV-2 virus in Calu-3 cells. Further, MM3122 blocks Middle East respiratory syndrome coronavirus (MERS-CoV) cell entry with an EC50 of 870 pM. MM3122 has excellent metabolic stability, safety, and pharmacokinetics in mice, with a half-life of 8.6 h in plasma and 7.5 h in lung tissue, making it suitable for in vivo efficacy evaluation and a promising drug candidate for COVID-19 treatment.

In recent years, there has been an increase in the prevalence of mental disorders connected with affective dysregulation and insecure attachment. Therefore, it is even more important to understand the interplay between an individual’s attachment representation and patterns of emotion regulation. To our knowledge, this is the first systematic review to examine this association. PsycInfo, PsyArticles, and PubMed were searched for studies that examined attachment-related differences in emotion regulation in adults. To examine the unconscious attachment representation, only studies using the Adult Attachment Interview or the Adult Attachment Projective Picture System were included. Thirty-seven peer-reviewed studies (with a total of 2006 subjects) matched the PICO criteria. Emotion regulation was measured via four objective approaches: autonomic nervous system, brain activity, biochemistry, or nonverbal behavior. Across all measurements, results reveal a significant correlation between attachment representation and emotion regulation. Secure attachment correlates consistently with balanced emotion regulation, whereas it is impaired in insecure and dysfunctional in unresolved attachment. Specifically, unresolved individuals display counterintuitive responses and fail to use attachment as a resource. Insecure-dismissing attachment is associated with an emotionally deactivating strategy, while on a physiological, biochemical, and nonverbal level, emotional stress is still present. There is still a lack of studies examining preoccupied individuals. In addition to interpreting the results, we also discuss the risk of bias, implications for psychotherapy and coaching, and an outlook for future research.

Background: Natural sounds are reportedly restorative, but most research has used one-off experiments conducted in artificial conditions. Research based on field experiments is still in its infancy. This study aimed to generate hypotheses on the restorative effects of listening to natural sounds on surgeons, representing professionals working in stressful conditions. Methods: Each of four surgeons (two experts and two residents) participated six times in an experiment where they took a 10-min break listening to natural sounds (four times) or without natural sounds (twice) after a surgical operation. We measured their skin conductance level, an indicator of sympathetic arousal, continuously during the break (measurement occasions N = 2520) and assessed their mood using two questionnaires before and after the break (N = 69 and N = 42). We also interviewed them after the break. Results: Based on statistical Linear Mixed-Effects modeling, we developed two hypotheses for further, more detailed studies: (H1) Listening to natural sounds after an operation improves surgeons’ mood. (H2) Inexperienced surgeons’ tension persists so long that the effect of natural sounds on their sympathetic arousal is negligible. Conclusions: This risk-free, easy-to-use means of stress alleviation through natural sounds could benefit highly-stressed people working indoors.

Supervised contrastive learning (SCL) has recently emerged as an alternative to conventional machine learning and deep neural networks. In this study, we propose an SCL model with data augmentation techniques using phase-resolved partial discharge (PRPD) in gas-insulated switchgear (GIS). To increase the fault data for training, we employ Gaussian noise adding, Gaussian noise scaling, random cropping, and phase shifting for supervised contrastive loss. The performance of the proposed SCL was verified by four types of faults in the GIS and on-site noise using an on-line ultra-high-frequency (UHF) partial discharge (PD) monitoring system. The experimental results show that the proposed SCL achieves a classification accuracy of 97.28% and outperforms the other algorithms, including support vector machines (SVM), multilayer perceptron (MLP), and convolution neural networks (CNNs) in terms of classification accuracy, by 6.8%, 4.28%, 2.04%, respectively.

IntroductionThe COVID-19 pandemic has affected the lifestyle and psychological well-being of millions of people.ObjectivesThe aim of the study was to assess the prevalence of psychopathological symptoms in the Russian population in the COVID- 19 pandemic context.MethodsWe used a socio-demographic questionnaire (20 questions) and a Short Scale for Psychopathological Symptom Checklist (SCL -32) (Derogatis 1977; Mitina, Gorbunova, 2011). 582 Russian residents (496 women and 86 men) aged 18-64 years participated in the online survey in May 2020.ResultsWomen were significantly more likely than men to have somatic dysfunctions (5.6±2.54vs4.8±1.9;p=0.001), interpersonal problems (6.97±2.9vs6.0±2.8; p=0.005), depression signs (6.9±3.2vs5.7±2.9;p=0.001) and anxiety disorders (6.8±2.8vs5.2 ±2.1;p=0.000), as well as sleep disorders (6.4±2.8vs5.9±2.1;p=0.049) and suicidal thoughts (4.2±1.8vs3.7±1.8;p=0.032). In addition, women are more hostile than men are (6.3±2.7 vs 5.1±2.3; p=0.000). Respondents under the age of 30 are more likely than older people to have interpersonal problems (p=0.286, p=0.000), as well as signs of depression (p=0.216, p=0.000), hostility (p=0.226, p=0.000) and psychoticism (p=0.203, p=0.000). Respondents’ low income is statistically associated with interpersonal problems (p=0.139,p=0.001), anxiety (p=0.131, p=0.002), hostility (p=0.156, p=0.000), psychoticism (p=0.137, p=0.001), and suicidal intentions (p=0.152,p=0.000). Among respondents whose relatives had COVID-19, signs of anxiety disorders (7.2±3vs3.5±2.9;p=0.027) and obsessive disorders (8.1±3.2 vs 7.3±2.6; p=0.029) were significantly more common than in the whole sample.ConclusionsThe study highlights socio-demographic factors of vulnerability to psychopathological symptoms in the COVID-19 pandemic context, which should be taken into account when organizing medical and psychological assistance to the population.