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The fluorescence kinetics in intact photosystem II (PS II) core particles from the cyanobacterium Thermosynechococcus elongatus is measured with picosecond resolution at room temperature in open reaction centers. The analysis of the overall trapping kinetics based on the theory of energy migration and trapping on lattices has shown that the charge separation kinetics in photosystem II is extremely trap-limited and not diffusion-to-the-trap limited.

Viola reichenbachiana (2 n = 4 x = 20) and V. riviniana (2 n = 8 x = 40) are closely related species widely distributed in Europe, often sharing the same habitat throughout their overlapping ranges. It has been suggested in numerous studies that their high intraspecific morphological variability and plasticity might have been further increased by interspecific hybridisation in contact zones, given the sympatry of the species and the incomplete sterility of their hybrid. The aims of this study were to: (i) confirm that V. reichenbachiana and V. riviniana have one 4 x genome in common, and (ii) determine the impact of hybridisation and introgression on genetic variation of these two species in selected European populations., For our study, we used 31 Viola populations from four European countries, which were analysed using AFLP and sequencing of a variable plastid intergenic spacer, trnH-psbA., Our analysis revealed that V. reichenbachiana exhibited larger haplotype diversity, having three species-specific haplotypes versus one in V. riviniana. The relationships among haplotypes suggest transfer of common haplotypes into V. riviniana from both V. reichenbachiana and hypothetically the other, now extinct, parental species. AFLP analysis showed low overall genetic diversity of both species, with V. riviniana showing higher among-population diversity. None of the morphologically designated hybrid populations had additive AFLP polymorphisms that would have indicated recent hybridisation. Also, kinship coefficients between both species did not indicate gene flow. V. riviniana showed significant population subdivision and significant isolation by distance, in contrast to V. reichenbachiana., The results indicate lack of gene flow between species, high influence of selfing on genetic variability, as well as probably only localised introgression toward V. riviniana. [ABSTRACT FROM AUTHOR]

A comparison of the Fourier transform Raman spectrum and the infrared spectrum of thymine isolated in an argon matrix is presented.

Morphological characters, AFLP markers and flow cytometry were used to investigate the morphological and genetic variability and differentiation of Viola reichenbachiana and V. riviniana in non-metallicolous ( NM) and metallicolous (M) populations. The aims were to clarify the taxonomic status of plants occurring in ore-bearing areas, to determine any relationship in V. reichenbachiana and V. riviniana from sites not polluted with heavy metals, and to examine the genetic variability and differentiation of M and NM populations of both species. Multivariate analyses based on morphological characters showed significant differences between V. reichenbachiana and V. riviniana from non-polluted sites, high levels of intra- and inter-population variability, and the occurrence of inter-specific hybrids. Plants from M populations showed hybrid characters but also fell within the range of V. riviniana or V. reichenbachiana. There were no significant differences in relative genome size between plants from polluted areas and V. riviniana from NM populations. Bayesian analysis of population genetic structure based on AFLP markers distinguished two main groups: V. reichenbachiana and V. riviniana together with the M populations. That analysis also revealed the occurrence of populations of inter-specific hybrids from non-polluted areas. Further Bayesian analysis of V. riviniana including NM and M populations separated all the studied M populations from NM populations. We conclude that plants forming the M populations are well adapted to a metal-polluted environment, and could be considered as stabilised introgressive forms resulting from unidirectional (asymmetric) introgression toward V. riviniana. [ABSTRACT FROM AUTHOR]

To determine the relative importance of clonal growth and sexual reproduction, the Randomly Amplified Polymorphic DNA (RAPD) method was used to study genetic diversity and clonal structure of six populations of Elymus repens and four populations of Elymus hispidus from Poland. These outbreeding species are virtually self-sterile and form widely spreading and long-lived rhizomes. Using 12 primers, a total of 150 unambiguous RAPD fragments were amplified and scored. Results ofAMOVA showed no significant genetic distinction between morphologically distinguished varieties of E. repens and E. hispidus. E. repens had slightly higher intra-specific genetic polymorphism than E. hispidus; the percentage of polymorphic bands per population ranged from 38 to 49 and from 19 to 38 respectively. Clonal diversity measured using the Simpson diversity index (D) indicated different contributions of clonal reproduction in particular populations of E. repens (D: 0.20–0.72). Populations of E. hispidus were dominated by one or a few clones, which were generally restricted to a single population (D: 0.00–0.22). RAPD revealed that most genetic diversity resided within populations of the two studied species, suggesting that, despite their clonal character, propagation by seeds contributes considerably to reproduction of E. repens and E. hispidus. [ABSTRACT FROM AUTHOR]

Over 3% of the entire Polish population migrate for a job within the European Union, most are aged 18-44 years. The main destinations are Germany, the United Kingdom and Ireland. Immigration is connected with the use of many public services, including healthcare services. Assuming Polish immigrants require medical consultations in the countries they reside in, the authors have analysed the reasons for patients' visits to general practitioners (GPs) in Poland in order to predict possible reasons why Polish patients living abroad may make appointments with GPs in other countries. Data from 22 769 visits to GP practices between June 2005 and May 2006 by Polish patients aged 18-44 years were collected electronically. Age was categorised into three groups (18-24, 25-34 and 35-44 years) and the reason for the visit was categorised according to the ICD 10 coding system. Among the 12 535 patients registered with GPs, 73.1% of women and 68.6% of men required consultations during the year the study was conducted. The highest percentage of visits was recorded for women aged 35-44 years, while men of the same age were the least likely to visit a GP. The mean number of visits per patient ranged from 1.89 for men aged 25-34 years to 3.11 for women aged 35-44 years. The means were similar for 18- to 24-year-old men and women. Women aged 35-44 years had a higher mean number of visits compared with women aged 18-24 years, whereas the opposite was true for men. The analysis of reasons for visits within the age groups indicated that the percentage of appointments for respiratory problems and general and unspecified problems dropped by more than half from the 18-24-year-olds to the 35-44-years-olds, while visits for musculosceletal, cardiovascular, and mental and behavioural problems increased by a factor of four. The presented results intend to enable healthcare services meet Polish immigrants' healthcare needs. [ABSTRACT FROM AUTHOR]

In 2002-2003, the American College of Medical Informatics (ACMI) undertook a study of the future of informatics training. This project capitalized on the rapidly expanding interest in the role of computation in basic biological research, well characterized in the National Institutes of Health (NIH) Biomedical Information Science and Technology Initiative (BISTI) report. The defining activity of the project was the three-day 2002 Annual Symposium of the College. A committee, comprised of the authors of this report, subsequently carried out activities, including interviews with a broader informatics and biological sciences constituency, collation and categorization of observations, and generation of recommendations. The committee viewed biomedical informatics as an interdisciplinary field, combining basic informational and computational sciences with application domains, including health care, biological research, and education. Consequently, effective training in informatics, viewed from a national perspective, should encompass four key elements: (1). curricula that integrate experiences in the computational sciences and application domains rather than just concatenating them; (2). diversity among trainees, with individualized, interdisciplinary cross-training allowing each trainee to develop key competencies that he or she does not initially possess; (3). direct immersion in research and development activities; and (4). exposure across the wide range of basic informational and computational sciences. Informatics training programs that implement these features, irrespective of their funding sources, will meet and exceed the challenges raised by the BISTI report, and optimally prepare their trainees for careers in a field that continues to evolve. [ABSTRACT FROM AUTHOR]

The current practise to focus periodic retesting of composite cylinders primarily on the hydraulic pressure test has to be evaluated as critical. The test itself always causes a certain amount of micro damage to the cylinders but does not necessarily deliver sufficient and evaluable information. Thus BAM Federal Institute of Materials Research and Testing (Germany) moves the focal point to a new approach for validation of composite cylinders, based on destructive sample tests parallel to operation. Statistical assessment of results of these destructive tests is employed for the estimation of remaining safe service life, based on reliability demands. The estimated service life is also used for the determination of re-test periods of the examined population of composite cylinders. An essential aspect of this approach is the validation of current residual strength and its prediction at any point of service life. In cases of gas cylinders with very high cycle strength, residual strength cannot be quantified statistically by means of hydraulic load cycles. As a replacement, creep tests or burst tests may be employed. BAM suggests the “slow burst test SBT” as a combination of these two test procedures. This is a compromise between the practicability of the (conventional) burst test and the practical relevance of sustained loads during service, to be tested in creep rupture tests. In this paper, a variety of 99 burst results of a cylinder design type used for breathing apparatus (CFRP with PE-liner) is evaluated. The influence of test procedure parameters and nature and intensity of artificial ageing on the test sample strength are analysed statistically. This leads to an evaluation of different procedures of artificial ageing and the recommendation to substitute conventional burst tests by slow burst tests for the assessment of composite pressure receptacles. [ABSTRACT FROM AUTHOR]

Colorectal carcinoma brain metastases (n = 60) were studied using next-generation sequencing and immunohistochemistry. RAS and BRAF mutations were detected in 58.2% and 7.3% of cases, respectively. Patients with RAS- and BRAF-mutant tumors could potentially benefit from the treatment with inhibitors. TP53 mutations were detected in 69.1% of metastases. Moreover, altered p53 expression was seen in 91.2% of cases. APC mutations were present in 41.8% of tumors. Diffuse nuclear accumulation of β-catenin was seen in 10.2% of metastases, although only 1 CTNNB1 mutant was identified. Nevertheless, targeting p53 and Wnt/β-catenin pathways may have potential therapeutic implications. Casein kinase 1α1 expression indicating susceptibility to protein kinase inhibitors, was seen in 95% metastases including 10 with strong immunoreactivity. The immune checkpoint marker CD276, a promising target for immunotherapy, was present on tumor cells in 50.8% of metastases and on stromal cells in almost all cases. PRAME, another immunotherapy target, was expressed in 21.7% of tumors. HER2 membrane immunostaining detected in 13.3% of cases implicated potential treatment with HER2 inhibitors. Expression of SLFN11, a predictor of response to DNA-damaging chemotherapies, and a biomarker of sensitivity to PARP inhibitors was seen in 8.3% of tumors. In 6.7% of metastases loss or partial loss of MTAP expression suggested sensitivity to PRMT5 inhibitors. CD44v5 expressed in 35% of cases indicated potential therapeutic utility of anti-CD44v5 monoclonal antibody treatment. Identification of predictive biomarkers through genomic profiling and proteomic analyses is a crucial step toward individually tailored therapeutic regimens for patients with colorectal carcinoma brain metastases., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Central Eastern European countries (CEEc) are characterized both by huge diversity in income inequality and, on average, by lower levels of well-being than in the other European Union (EU) countries. Given that income inequality may affect well-being negatively, the present study aims to explore the links between income inequalities and different dimensions of well-being in the eight CEEc, i.e. Poland, Czech Republic, Slovakia, Slovenia, Hungary, Latvia, Lithuania, and Estonia. The analysis is conducted in the two groups of CEEc regarding low and high inequality in income distribution, namely CEE Continental group and CEE North group (corresponding to post-socialist corporatist and post-socialist liberal, respectively). The multidimensional concept of well-being is applied, enabling deep exploration of its links with income inequalities in the following dimensions: subjective well-being (happiness) and objective well-being (material, health, educational, and environmental dimensions). We estimate the vector autoregression (VAR) models based on annual data disaggregated into quarterly data covering 2004 to 2020. The empirical results of Granger causality testing, which was used to investigate the links between income inequality and multidimensional well-being, indicated that not only are there differences between the groups in the studied patterns of interconnectedness, but also the groups of CEE North and CEE Continental countries are not homogeneous in those links., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Geise, Szczepaniak. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Climate change and intense human activity are exacerbating changes in species' ranges. While the rapid spread of invasive alien species is well documented worldwide, the phenomenon of the spread of native species is poorly understood. To explain the problem of rapidly spreading species in the changing world, it is necessary to understand their ecology, genetic diversity and habitat limitation. The aim of our study was to analyze the ecological requirements and genetic diversity in the population of the macrophyte Trapa natans s. l., an invasive alien species in North America but native in Europe and Asia. We investigated the populations in its native range (Central and Northeastern Europe), where the species is defined as rare or extinct. We found the occurrence of T. natans in Northeastern Europe aquatic habitats where, up to now, it was described as an extinct species. The results of our environmental studies showed that the species has a wide range of tolerance to habitat conditions and lives in medium to highly nutrient-rich water with low and high salinity. Using Amplified Fragment Length Polymorphism (AFLP) analysis, we revealed high genetic variability within populations with relatively limited differentiation between populations. We showed that some populations are highly diverse (possibly refugia; Central Europe) and others are homogeneous (new sites, commercial reintroduction; Northeastern Europe). Conservation status of T. natans in its native range should be reconsidered, as the species has spread rapidly in recent decades and could be detrimental to aquatic habitats. The conclusion is that expansion/invasion can start from small populations, but under favorable conditions these populations spread rapidly. The introduction of species (even native) should be done carefully, if at all, as uncontrolled introduction to new locations, e.g. private ponds, could be the start of dispersal (native habitats) or invasion (non-native area)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite the wealth of data available for mountain phylogeography, local-scale studies focused on narrow endemic species remain rare. Yet, knowledge of the genetic structure of such species biogeographically linked to a restricted area is of particular importance to understand the history of the local flora and its diversity patterns. Here, we aim to contribute to the phylogeographical overview of the Western Carpathians with a genetic study of Saxifragawahlenbergii , one of the most characteristic endemic species of this region. We sampled populations from all discrete parts of the species' distribution range to apply sequencing of selected non-coding cpDNA and nuclear ribosomal DNA (ITS) regions, as well as Amplified Fragment Length Polymorphism (AFLP) fingerprinting. First, while ITS sequences showed weak diversification, the genetic structure based on cpDNA sequences revealed two well-differentiated groups of haplotypes. One of them is restricted to the main center of the distribution range in the Tatra Mountains (Mts), while the second group included a series of closely related haplotypes, which in most cases were unique for particular isolated groups of populations in peripheral mountain ranges and in the south-eastern part of the Tatra Mts. AFLP fingerprinting also revealed a pattern of divergence among populations, while only partly corroborating the division observed in cpDNA. Taking into account all the data, the pattern of genetic structure, supported by the high levels of unique genetic markers in populations, may reflect the historical isolation of populations in several local refugia during the last glacial period. Not only the center of the range in the Tatra Mts, but also other, neighboring massifs (Malá Fatra, Nízke Tatry, Chočské vrchy, Muránska planina), where populations are characterized by separate plastid DNA haplotypes, could have acted as separate refugia., Competing Interests: The authors have declared that no competing interests exist., (Elżbieta Cieślak, Michał Ronikier, Magdalena Szczepaniak.)

Introduction: Corticotroph pituitary neuroendocrine tumors (PitNETs) develop from ACTH-producing cells. They commonly cause Cushing's disease (CD), however, some remain clinically silent. Recurrent USP8 , USP48 , BRAF and TP53 mutations occur in corticotroph PitNETs. The aim of our study was to determine frequency and relevance of these mutations in a possibly large series of corticotroph PitNETs., Methods: Study included 147 patients (100 CD and 47 silent tumors) that were screened for hot-spot mutations in USP8 , USP48 and BRAF with Sanger sequencing, while 128 of these patients were screened for TP53 mutations with next generation sequencing and immunohistochemistry., Results: USP8 mutations were found in 41% CD and 8,5% silent tumors, while USP48 mutations were found in 6% CD patients only. Both were more prevalent in women. They were related to higher rate of biochemical remission, non-invasive tumor growth, its smaller size and densely granulated histology, suggesting that these mutation may be favorable clinical features. Multivariate survival analyses did not confirm possible prognostic value of mutation in protein deubiquitinases. No BRAF mutations were found. Four TP53 mutations were identified (2 in CD, 2 in silent tumors) in tumors with size >10mm including 3 invasive ones. They were found in Crooke's cell and sparsely granulated tumors. Tumors with missense TP53 mutations had higher TP53 immunoreactivity score than wild-type tumors. Tumor with frameshift TP53 variant had low protein expression. TP53 mutation was a poor prognostic factor in CD according to uni- and multivariate survival analyses in spite of low mutations frequency., Conclusions: We confirmed high prevalence of USP8 mutations and low incidence of USP48 and TP53 mutations. Changes in protein deubiquitinases genes appear to be favorable prognostic factors in CD. TP53 mutations are rare, occur in both functioning and silent tumors and are related to poor clinical outcome in CD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pękul, Szczepaniak, Kober, Rusetska, Mossakowska, Baluszek, Kowalik, Maksymowicz, Zieliński, Kunicki, Witek and Bujko.)

Despite the introduction of new molecular classifications, advanced colorectal cancer (CRC) is treated with chemotherapy supplemented with anti-EGFR and anti-VEGF targeted therapy. In this study, 552 CRC cases with different primary tumor locations (250 left side, 190 rectum, and 112 right side) were retrospectively analyzed by next generation sequencing for mutations in 50 genes. The most frequently mutated genes were TP53 in left-sided tumors compared to right-sided tumors and BRAF in right-sided tumors compared to left-sided tumors. Mutations in KRAS, NRAS, and BRAF were not detected in 45% of patients with left-sided tumors and in 28.6% of patients with right-sided tumors. Liver metastases were more common in patients with left-sided tumors. Tumors on the right side were larger at diagnosis and had a higher grade (G3) than tumors on the left. Rectal tumors exhibit distinctive biological characteristics when compared to left-sided tumors, including a higher absence rate of KRAS, NRAS, and BRAF mutations (47.4% in rectal versus 42.8% in left-sided tumors). These rectal tumors are also unique in their primary metastasis site, which is predominantly the lungs, and they have varying mutation rates, particularly in genes such as BRAF, FBXW7, and TP53, that distinguish them from tumors found in other locations. Primary tumor location has implications for the potential treatment of CRC with anti-EGFR therapy., (© 2024. The Author(s).)

Synovial sarcoma is a relatively common soft tissue tumor characterized by highly specific t(X;18)(p11;q11) translocation resulting in the fusion of SS18 with members of SSX gene family. Typically, detection of SS18 locus rearrangement by fluorescence in situ hybridization or SS18 :: SSX fusion transcripts confirms the diagnosis. More recently, immunohistochemistry (IHC) for SS18-SSX chimeric protein (E9X9V) and C-terminus of SSX (E5A2C) showed high specificity and sensitivity for synovial sarcoma. This study screened a cohort of >1000 soft tissue and melanocytic tumors using IHC and E9X9V and E5A2C antibodies. Three percent (6/212) of synovial sarcomas were either negative for SS18-SSX or had scattered positive tumor cells (n=1). In these cases, targeted RNA next-generation sequencing detected variants of SS18 :: SSX chimeric transcripts. DNA methylation profiles of 2 such tumors matched with synovial sarcoma. A few nonsynovial sarcoma tumors (n=6) revealed either focal SS18-SSX positivity (n=1) or scattered positive tumor cells. However, targeted RNA next-generation sequencing failed to detect SS18 :: SSX transcripts in these cases. The nature of this immunopositivity remains elusive and may require single cell sequencing studies. All synovial sarcomas showed positive SSX IHC. However, a mosaic staining pattern or focal loss of expression was noticed in a few cases. Strong and diffuse SSX immunoreactivity was also seen in epithelioid sclerosing osteosarcoma harboring EWSR1 :: SSX1 fusion, while several sarcomas and melanocytic tumors including cellular blue nevus (5/7, 71%) revealed focal to diffuse, mostly weak to intermediate SSX staining. The SS18-SSX and SSX IHC is a useful tool for synovial sarcoma differential diagnosis, but unusual immunophenotype should trigger molecular genetic testing., Competing Interests: Conflicts of Interest and Source of Funding: Supported as a part of NCI’s intramural research program. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Bladder cancer is a common malignancy associated with high recurrence rates and potential progression to invasive forms. Sorafenib, a multi-targeted tyrosine kinase inhibitor, has shown promise in anti-cancer therapy, but its cytotoxicity to normal cells and aggregation in solution limits its clinical application. To address these challenges, we investigated the formation of supramolecular aggregates of sorafenib with Congo red (CR), a bis-azo dye known for its supramolecular interaction. We analyzed different mole ratios of CR-sorafenib aggregates and evaluated their effects on bladder cancer cells of varying levels of malignancy. In addition, we also evaluated the effect of the test compounds on normal uroepithelial cells. Our results demonstrated that sorafenib inhibits the proliferation of bladder cancer cells and induces apoptosis in a dose-dependent manner. However, high concentrations of sorafenib also showed cytotoxicity to normal uroepithelial cells. In contrast, the CR-BAY aggregates exhibited reduced cytotoxicity to normal cells while maintaining anti-cancer activity. The aggregates inhibited cancer cell migration and invasion, suggesting their potential for metastasis prevention. Dynamic light scattering and UV-VIS measurements confirmed the formation of stable co-aggregates with distinctive spectral properties. These CR-sorafenib aggregates may provide a promising approach to targeted therapy with reduced cytotoxicity and improved stability for drug delivery in bladder cancer treatment. This work shows that the drug-excipient aggregates proposed and described so far, as Congo red-sorafenib, can be a real step forward in anti-cancer therapies.

Exosomes are secreted to the extracellular milieu when multivesicular endosomes (MVEs) dock and fuse with the plasma membrane. However, MVEs are also known to fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane for exosome secretion rather than to lysosomes is unclear. Here we report that a conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed sequentially by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. We further demonstrate that disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes. Together, our study suggests that the PI(3)P to PI(4)P conversion on MVEs and the recruitment of the exocyst direct the exocytic trafficking of MVEs for exosome secretion., (© 2023. The Author(s).)

Fluorescence nanoscopy has become increasingly powerful for biomedical research, but it has historically afforded a small field-of-view (FOV) of around 50 μm × 50 μm at once and more recently up to ∼200 μm × 200 μm. Efforts to further increase the FOV in fluorescence nanoscopy have thus far relied on the use of fabricated waveguide substrates, adding cost and sample constraints to the applications. Here we report PRism-Illumination and Microfluidics-Enhanced DNA-PAINT (PRIME-PAINT) for multiplexed fluorescence nanoscopy across millimeter-scale FOVs. Built upon the well-established prism-type total internal reflection microscopy, PRIME-PAINT achieves robust single-molecule localization with up to ∼520 μm × 520 μm single FOVs and 25-40 nm lateral resolutions. Through stitching, nanoscopic imaging over mm 2 sample areas can be completed in as little as 40 min per target. An on-stage microfluidics chamber facilitates probe exchange for multiplexing and enhances image quality, particularly for formalin-fixed paraffin-embedded (FFPE) tissue sections. We demonstrate the utility of PRIME-PAINT by analyzing ∼10 6 caveolae structures in ∼1,000 cells and imaging entire pancreatic cancer lesions from patient tissue biopsies. By imaging from nanometers to millimeters with multiplexity and broad sample compatibility, PRIME-PAINT will be useful for building multiscale, Google-Earth-like views of biological systems., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Co-published by Nanjing University and American Chemical Society.)

The United States Department of Agriculture's Gus Schumacher Nutrition Incentive Program (GusNIP) supports nutrition incentive (NI) and produce prescription programs (PPRs). PPRs allow healthcare providers to "prescribe" fruits and vegetables (FVs) to patients experiencing low income and/or chronic disease(s) and who screen positive for food insecurity. We developed a Theory of Change (TOC) that summarizes how and why PPRs work, identifies what the programs hope to achieve, and elucidates the causal pathways necessary to achieve their goals. We created the PPR TOC through an iterative, participatory process that adapted our previously developed GusNIP NI TOC. The participatory process involved food and nutrition security experts, healthcare providers, PPR implementors, and PPR evaluators reviewing the existing NI TOC and suggesting modifications to accurately reflect PPRs. The resulting TOC describes the mechanisms, assumptions, rationale, and underpinnings that lead to successful and equitable outcomes. Modifications of the NI TOC centered around equity and focused on inclusion of healthcare as an additional partner and the importance of health and healthcare utilization as outcomes. The TOC describes how the GusNIP PPR program reaches its goals. This understanding will be useful for PPR developers, implementers, funders, and evaluators for describing the pathways, assumptions, and foundations of successful PPRs.

Background: Student burnout during medical education is a prevalent and critical problem. Burnout has reaching consequences, including negative health outcomes for students, financial loss for schools, and worsened patient care as students transition to practice. Global Health Outreach Experiences (GHOEs), known to enhance cultural awareness and clinical knowledge among medical students, are offered in most programs. Prior studies document that GHOEs benefit physicians suffering from burnout, with effects demonstrating improvement over 6 months. No study, to our knowledge, has assessed the influence GHOEs may have on medical student burnout with a comparable control group. This study examines whether participation in a GHOE, compared to a standard break from school, has a positive effect on burnout., Methods: A case control study utilizing the Copenhagen Burnout Inventory was conducted on medical students. 41 students participated in a one-week, spring break GHOE and 252 were randomly selected as non-participating students in a control group. Assessments were gathered 1 week prior, 1 week after, and 10 weeks after spring break. Response across the surveys in chronological order included 22, 20, 19 GHOE and 70, 66, 50 control participants., Results: A significant reduction in personal burnout (PB) (P = 0.0161), studies related burnout (SRB) (P = 0.0056), and colleagues related burnout (CRB) (P = 0.0357) was found among GHOE attendees compared to control participants at 10-weeks after spring break. When modeled with potential confounders, CRB and SRB reductions remained significant., Conclusion: GHOEs may be a potential tool for institutions to combat burnout rates in their students. The benefits of GHOEs appear to enhance over time., (© 2023. The Author(s).)

Background: Although pregnancy is a physiological process it causes hormonal changes that can also affect the oral cavity. Pregnancy increases the risk of gum disease inflammation and tooth caries which could affect the health of the developing baby. Proper oral health is crucial both for mother and her babies and is related with mothers' awareness of this connection. The aim of this study was the self-assessment of women's both oral health and oral health literacy as well as mothers' awareness of the connection of oral health and pregnancy., Material and Methods: In the study anonymous questionnaire was prepared and provided to be filled in by 200 mothers at the age from 19 to 44 y.o. who gave birth in the gynecological clinic. The questionnaire included demographic, and concerning the areas of oral health before and during pregnancy and after the childbirth questions., Results: Only 20% of the investigated women underwent the oral examination before the pregnancy and the next 38.5% underwent it intentionally when the pregnancy had been confirmed. As much as 24% of women pointed out lack of awareness of the importance of proper oral hygiene during pregnancy. 41.5% of investigated women declared complaints during the pregnancy concerning teeth or gums and 30.5% underwent dental treatment; 68%, brushed their teeth properly-twice a day; 32% of women observed deterioration of oral health state during the pregnancy. The knowledge of the importance of oral health during pregnancy presented by the majority of mothers was relatively proper, which was strongly connected with higher education status and living in big cities. A significant correlation between higher birth weight and more frequent daily tooth brushing was observed. Both higher frequency of problems concerning the oral cavity and dental treatment during pregnancy were significantly related to the younger age of mothers., Conclusions: The knowledge of women concerning of oral health on the management of pregnancy and development of fetus is still insufficient. Gynecologists should inquire pregnant women if they have done dental examination, and provide wider education about importance of oral health in pregnancy., (© 2023. The Author(s).)

Background: A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression., Methods: Clinical material was obtained from 89 patients with VSCC. Next-generation sequencing (NGS) of 16S rRNA and quantitative polymerase chain reaction (qPCR) were used to detect bacterial species in VSCC. To verify neutrophil activation, CD66b expression in tumour specimens was analysed by immunohistochemistry (IHC). Subsequently, IHC was applied to detect the main neutrophil serine proteases (NSPs), cathepsin G (CTSG), neutrophil elastase (ELANE), and proteinase 3 (PRTN3) in VSCC., Results: Fusobacterium nucleatum and Pseudomonas aeruginosa were identified as tumour-promoting bacteria, and their presence was found to be associated with a shorter time to progression in VSCC patients. Furthermore, high abundance of CD66b, the neutrophil activation marker, in VSCC samples, was found to relate to poor survival of patients with VSCC. The selected NSPs were shown to be expressed in vulvar tumours, also within microabscess. The increased numbers of microabscesess were correlated with poor survival in VSCC patients., Conclusions: Our results show that neutrophilic inflammation seem to be permissive for tumour-promoting bacteria growth in VSCC. The findings provide new therapeutic opportunities, such as based on shifting the balance of neutrophil populations to those with antitumorigenic activity and on targeting NSPs produced by activated neutrophils at the inflammation sites., (© 2023. The Author(s).)

Objective: To explore the approaches applied by nutrition educators who work with the US Department of Agriculture Gus Schumacher Nutrition Incentive Program (GusNIP), Nutrition Incentive (NI), and Produce Prescription (PPR) programs., Methods: Multiple data collection methods, including descriptive survey (n = 41), individual interviews (n = 25), and 1 focus group (n = 5). Interviewees were educators who deliver nutrition education as a component of GusNIP NI/PPR programs. Descriptive statistics were calculated from survey responses. Transcripts were coded using thematic qualitative analysis methods., Results: Four overarching themes emerged. First, educators have many roles and responsibilities beyond providing curriculum-based nutrition education. Second, interviewees emphasized participant-centered nutrition education and support. Third, partnerships with collaborating cross-sector organizations are essential. Fourth, there are common challenges to providing nutrition education within GusNIP NI/PPR programs, and educators proposed solutions to mitigate these challenges., Conclusions: Nutrition educators promote multilevel solutions to improve dietary intake, and it is recommended they be included in conversations to improve GusNIP NI/PPR programs., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The laser treatment of surfaces enables the alteration of their morphology and makes them suitable for various applications. This paper discusses the use of a laser beam to develop surface features that enhance pool boiling heat transfer. Two types of structures (in the 'macro' and 'micro' scale) were created on the samples: microfins (grooves) and surface roughness. The impact of the pulse duration and scanning velocity on the height of the microfins and surface roughness at the bottom of the grooves was analyzed with a high precision optical profilometer and microscope. The results indicated that the highest microfins and surface roughness were obtained with a pulse duration of 250 ns and scanning velocity of 200 mm/s. In addition, the influence of the 'macro' and 'micro' scale modifications on the boiling heat transfer of distilled water and ethyl alcohol was studied on horizontal samples heated with an electric heater. The largest enhancement was obtained for the highest microfins and roughest surfaces, especially at small superheats. Heat flux dissipated from the samples containing microfins of 0.4 mm height was, maximally, over three times (for water) and two times (for ethanol) higher than for the samples with smaller microfins (0.2 mm high). Thus, a modification of a selected model of boiling heat transfer was developed so that it would be applicable to laser-processed surfaces. The correlation proved to be quite successful, with almost all experimental data falling within the ±100% agreement bands.

Objectives: In this first large-scale analysis of neurological emergency admissions in England, we determine the number and types of emergency admissions with neurological emergency diagnostic codes, how many are under the care of a neurologist or neurosurgeon and how such admissions vary by levels of deprivation., Design: Retrospective empirical research employing a derived list of neurological emergency diagnostic codes SETTING: This study used the Hospital Episode Statistics data set for the financial year 2019/2020 based on 17 million in-year inpatient admissions in England including 6.5 million (100%) emergency admissions with any diagnosis codes., Results: There were 1.4 million (21.2%) emergency inpatient admissions with a mention of any neurological code, approx. 248 455 (3.8%) with mention of a specific neurological emergency code from the derived list, and 72 485 (1.1%) included such a code as the primary reason for admission. The highest number of in-year admissions for adults was for epilepsy (145 995), with epilepsy as the primary diagnostic code in 15 945 (10.9%). Acute nerve root/spinal cord syndrome (41 215), head injury (29 235) and subarachnoid haemorrhage (18 505) accounted for the next three highest number of admissions. 3230 (1.4%) in-year emergency hospital admissions with mention of a neurological emergency code were under the care of a neurologist or neurosurgeon, with only 1315 (0.9%) admissions with mention of an epilepsy code under a neurologist. There was significant variation for epilepsy and functional neurological disorders (FNDs) in particular by Index of Multiple Deprivation decile. The association between deprivation and epilepsy and FND was significant with p-values of 2.5e-6 and 1.5e-8, respectively., Conclusions: This study has identified important findings in relation to the burden of neurological emergency admissions but further work is needed, with greater clinical engagement in diagnostic coding, to better understand the implications for workforce and changes to service delivery needing to be implemented., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Recent advances in super resolution microscopy have enabled imaging at the 10-20 nm scale on a light microscope, providing unprecedented details of native biological structures and processes in intact and hydrated samples. Of the existing strategies, DNA points accumulation in imaging nanoscale topography (DNA-PAINT) affords convenient multiplexing, an important feature in interrogating complex biological systems. A practical limitation of DNA-PAINT, however, has been the slow imaging speed. In its original form, DNA-PAINT imaging of each target takes tens of minutes to hours to complete. To address this challenge, several improved implementations have been introduced. These include DNA-PAINT-ERS (where E = ethylene carbonate; R = repeat sequence; S = spacer), a set of strategies that leads to both accelerated DNA-PAINT imaging speed and improved image quality. With DNA-PAINT-ERS, imaging of typical cellular targets such as microtubules takes only 5-10 min. Importantly, DNA-PAINT-ERS also facilitates multiplexing and can be easily integrated into current workflows for fluorescence staining of biological samples. Here, we provide a detailed, step-by-step guide for fast and multiplexed DNA-PAINT-ERS imaging of fixed and immunostained cells grown on glass substrates as adherent monolayers. The protocol should be readily extended to biological samples of a different format (for example tissue sections) or staining mechanisms (for example using nanobodies). © 2022 Wiley Periodicals LLC. Basic Protocol 1: Preparation of probes for DNA-PAINT-ERS Basic Protocol 2: Sample preparation for imaging membrane targets with DNA-PAINT-ERS in fixed cells Alternate Protocol: Immunostaining of extracted U2OS cells Basic Protocol 3: Super resolution image acquisition and analysis., (© 2022 Wiley Periodicals LLC.)

Sinonasal mucosal melanoma is a rare tumor arising within the nasal cavity, paranasal sinuses, or nasopharynx (sinonasal tract). This study evaluated 90 cases diagnosed in 29 males and 61 females with median age 68 years. Most tumors involved the nasal cavity and had an epithelioid morphology. Spectrum of research techniques used in this analysis includes targeted-DNA and -RNA next-generation sequencing, Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry. Sinonasal melanomas were commonly driven by RAS (38/90, 42%), especially NRAS (n = 36) mutations and rarely (4/90, 4%) displayed BRAF pathogenic variants. BRAF/RAS mutants were more frequent among paranasal sinuses (10/14, 71%) than nasal (26/64, 41%) tumors. BRAF/RAS-wild type tumors occasionally harbored alterations of the key components and regulators of Ras-MAPK signaling pathway: NF1 mutations (1/17, 6%) or NF1 locus deletions (1/25, 4%), SPRED1 (3/25, 12%), PIK3CA (3/50, 6%), PTEN (4/50, 8%) and mTOR (1/50, 2%) mutations. These mutations often occurred in a mutually exclusive manner. In several tumors some of which were NRAS mutants, TP53 was deleted (6/48, 13%) and/or mutated (5/90, 6%). Variable nuclear accumulation of TP53, mirrored by elevated nuclear MDM2 expression was seen in >50% of cases. Furthermore, sinonasal melanomas (n = 7) including RAS/BRAF-wild type tumors (n = 5) harbored alterations of the key components and regulators of canonical WNT-pathway: APC (4/90, 4%), CTNNB1 (3/90, 3%) and AMER1 (1/90, 1%). Both, TERT promoter mutations (5/53, 9%) and fusions (2/40, 5%) were identified. The latter occurred in BRAF/RAS-wild type tumors. No oncogenic fusion gene transcripts previously reported in cutaneous melanomas were detected. Eight tumors including 7 BRAF/RAS-wild type cases expressed ADCK4::NUMBL cis-fusion transcripts. In summary, this study documented mutational activation of NRAS and other key components and regulators of Ras-MAPK signaling pathway such as SPRED1 in a majority of sinonasal melanomas., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Recent work suggests that Ras small GTPases interact with the anionic lipid phosphatidylserine (PS) in an isoform-specific manner, with direct implications for their biological functions. Studies on PS-Ras associations in cells, however, have relied on immuno-EM imaging of membrane sheets. To study their spatial relationships in intact cells, we have combined the use of Lact-C2-GFP, a biosensor for PS, with multicolor super resolution imaging based on DNA-PAINT. At ~20 nm spatial resolution, the resulting super resolution images clearly show the nonuniform molecular distribution of PS on the cell membrane and its co-enrichment with caveolae, as well as with unidentified membrane structures. Two-color imaging followed by spatial analysis shows that KRas-G12D and HRas-G12V both co-enrich with PS in model U2OS cells, confirming previous observations, yet exhibit clear differences in their association patterns. Whereas HRas-G12V is almost always co-enriched with PS, KRas-G12D is strongly co-enriched with PS in about half of the cells, with the other half exhibiting a more moderate association. In addition, perturbations to the actin cytoskeleton differentially impact PS association with the two Ras isoforms. These results suggest that PS-Ras association is context-dependent and demonstrate the utility of multiplexed super resolution imaging in defining the complex interplay between Ras and the membrane.

Introduction: In the following study we describe the diagnostic process and further case analysis of a 30-year-old woman admitted with typical COVID-19 symptoms, who subsequently developed additional symptoms suggesting cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL)., Material and Methods: Other than the standard diagnostic procedures, whole genome sequencing (WGS) was used, which led to following findings. A new variant of the NOTCH3 gene, which led to CADASIL-like symptoms, was found, and it had been most likely activated by the SARS-CoV-2 infection. This novel variant in NOTCH3 has not been found in existing databases and has never been mentioned in research concerning CADASIL before., Results: Furthermore, after subjecting the patient's close relatives to WGS it was found that no other examined person demonstrated the same genetic mutation., Conclusions: It seems therefore that the new variant of NOTCH3 is of de novo origin in the patient's genome. Additionally, the relatively early onset of CADASIL and the unexpectedly severe COVID-19 infection suggest that the two occurred simultaneously: the infection with SARS-CoV-2 accelerated development of CADASIL symptoms and the unusual variant of the NOTCH3 gene contributed to the more severe course of COVID-19., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia & Banach.)

A new nivicolous myxomycete is described as a result of a comprehensive study of Didymium nivicola collections from the entire range of its occurrence. Statistical analysis of 12 morphological characters, phylogenetic analyses of nuc 18S rDNA and elongation factor 1-alpha gene ( EF1A ), and a delimitation method (automatic barcode gap diversity) have been applied to corroborate the identity of the new species. A preliminary morphological analysis of D. nivicola revealed high variability of South American populations where four types of spore ornamentation were noted. However, results of molecular study and statistical analysis of morphological characters did not support recognition of these four forms but the distinction of two morphotypes. Consequently, two species have been recognized: D. nivicola and the newly proposed D. pseudonivicola . The new species can be distinguished from D. nivicola by distinctly larger and mostly plasmodiocarpic sporophores, which are scattered to gregarious, paler spores, and by the paler, more delicate and more elastic capillitium. Spore ornamentation of D. pseudonivicola is uniform and can be described as distinctly spiny (pilate under scanning electron microscope [SEM]), whereas those of D. nivicola is more variable, where spines (pilae under SEM) are delicate, distinct, or conspicuous. Additionally, whereas D. nivicola is a species distributed worldwide, D. pseudonivicola occurs only in the austral Andes of Argentina and Chile.

This article examines the relationships between different dimensions of well-being and income inequalities across selected Central Eastern European countries after joining the European Union in 2004. Regarding the multivariety of well-being concept, it explores its 5 dimensions (material dimension, health dimension, education dimension, environmental dimension, happiness). Accounting for the interactions between dimensions of well-being matters for the inequalities, we conducted an in-depth analysis by adopting PMG estimation and panel ARDL model to assess the short-run and long-run links between variables. The results of conducted analysis allowed us to identify the canals through which income inequalities are linked directly or indirectly with the particular dimensions of well-being. In the long run, all the dimensions of well-being significantly affected income inequalities, and income inequality shaped material dimension, health, education, natural environment, and happiness. However, in the short run, the only dimension that shaped income inequalities was education. Income inequalities directly affected both health dimension and happiness., Competing Interests: The authors have declared that no competing interests exist.

Background: Borderline personality disorder (BPD) is characterized by instability in affective regulation that can result in a loss of cognitive control. Triggers may be neuronal responses to emotionally valenced context and/or stimuli. 'Neuronal priming' indexes the familiarity of stimuli, and may capture the obligatory effects of affective valence on the brain's processing system, and how such valence mediates responses to the repeated presentation of stimuli. We investigated the effects of affective valence of stimuli on neuronal priming (i.e. changes in activation to repeated presentation of stimuli), and if these effects distinguished BPD patients from controls., Methods: Forty BPD subjects and 25 control subjects (age range: 18-44) participated in an episodic memory task during fMRI. Stimuli were presented in alternating epochs of encoding (six images of positive, negative, and neutral valence) and recognition (six images for 'old' v. 'new' recognition). Analyses focused on inter-group differences in the change in activation to repeated stimuli (presented during Encoding and Recognition)., Results: Relative to controls, BPD showed greater priming (generally greater decrease from encoding to recognition) for negatively valenced stimuli. Conversely, BPD showed less priming for positively valenced stimuli (generally greater increase from encoding to recognition)., Conclusion: Plausibly, the relative familiarity of negative valence to patients with BPD exerts an influence on obligatory responses to repeated stimuli leading to repetition priming of neuronal profiles. The specific effects of valence on memory and/or attention, and consequently on priming can inform the understanding of mechanisms of altered salience for affective stimuli in BPD.

Background: Palmoplantar pustulosis (PPP) is a chronic inflammatory disease with poorly understood pathogenesis. The disease has a chronic course with improvements and exacerbations. Due to palmoplantar location, PPP has a severely negative impact on patients' quality of life., Objectives: To identify demographic and environmental factors, concomitant diseases, medications, and bacterial factors which may affect the course of PPP., Material and Methods: A total of 51 patients suffering from PPP took part in the study. They were classified according to the Palmoplantar Pustulosis Psoriasis Area and Severity Index (ppPASI) into 3 groups due to the severity of the disease. Pack-year of smoking score was established as a quotient of packets smoked every 24 h and the years of being addicted. Diagnosis of metabolic syndrome was based on the IDF criteria from 2009. Chlamydia trachomatis was detected using enzyme-linked immunosorbent assay (ELISA) technique, Staphylococcus aureus by the culture swabs. Contact hypersensitivity was examined with the T.R.U.E. test., Results: Significantly high severity of PPP was observed in patients addicted to smoking with a high pack-year score (p = 0.03). Significantly lower intensity of PPP lesions was observed in patients treated with ibuprofen (p < 0.01). There was no correlation between severity of PPP skin lesions and comorbidities., Conclusions: Addiction to cigarette smoking and a high pack-year score aggravates the course of PPP. Treatment with ibuprofen can improve the course of the disease.

The main objective of the present work is to determine the effects of laser processing on properties of WC-Co electro-spark deposited (ESD) coatings on steel substrates. Tungsten carbide coatings have been applied to steel substrates using a manual electrode feeder, model EIL-8A. The laser beam processing (LBP) of electro-spark coatings was performed using an Nd:YAG fiber laser. The microstructure and properties of laser treated/melted coatings were evaluated by means of scanning electron microscopy (SEM), X-ray diffraction (XRD), surface geometric structure (SGS) and roughness measurements and adhesion, microhardness, residual stresses, corrosion resistance and application tests. The obtained experimental data were subjected to statistical analysis and multidimensional numerical and visual exploratory techniques. It has been shown conclusively that the laser-treated ESD WC-Co coatings are characterized by lower microhardness, higher resistance to corrosion, increased roughness and better adhesion to the substrate. LBP homogenizes the chemical composition, refines the microstructure and heals microcracks and pores of ESD coatings. The laser treated ESD WC-Co coatings can be used in frictional sliding nodes (e.g., on the front seal rings used in pumps) and as protective layers.

Purpose: The aim of this work was to determine anaerobic performance in male amputee football players considering types and levels of limb impairment, playing position, anthropometric parameters, and comparing the findings to reference values. Relationship between parameters in the laboratory anaerobic test and the handgrip test was checked., Methods: The 30-second Wingate Anaerobic Test (peak power, mean power, relative peak power, relative mean power, time to achieve peak power, fatigue index) on the arm-crank ergometer (LODE ANGIO), the FUTREX 6100 (Futrex, Gaithersburg, USA) and the handgrip test were used in amputee football players (n = 23). Anthropometric measurements were collected., Results: There were no differences in anaerobic results between players considering types and levels of limb impairment. Forwards had significantly higher relative mean and peak power ( p = 0.049, d = 0.82; p = 0.049, d = 0.81), and lower amputation-adjusted body mass index ( p = 0.001, d = 1.50) than defenders. For peak power, 19 out 23 achieved, and for relative peak power, 22 out 23 achieved results from "average" to "elite". Peak power strongly correlated to handgrip strength results., Conclusions: Amputee football requires a high level of power from players. Maintaining appropriate body composition is important for amputee football players to have better anaerobic performance during the game. The 30-second Wingate Anaerobic Test can be used to assess anaerobic performance in AF players. Sport-specific anaerobic performance laboratory tests and field-based tests using in indirect upper limbs' peak power monitoring would be beneficial for coaches.

Background: Migration is a challenging life transition that may be a source of various problems related to well-being and mental health. However, the psychological adaptation of migrants may be potentially facilitated by social self-efficacy-the beliefs in one's ability to initiate and maintain interpersonal relationships. Previous research suggests that social self-efficacy is positively related to adjustment and negatively related to loneliness, depression, and psychological distress. Research also confirms that self-efficacy beliefs can be effectively enhanced using Internet-based interventions. These results served as a background for creating the New in Town, a self-help Internet-based intervention for internal migrants in Poland that aims at increasing social self-efficacy. Exercises in the intervention are based on the principles of Cognitive Behavioral Therapy and relate to sources of self-efficacy beliefs: mastery experiences, vicarious experiences, verbal persuasions, and emotional and physiological states. Users complete increasingly challenging tasks that encourage them to interact with their environment. The aim of this trial was to investigate the efficacy of the New in Town intervention., Methods: The efficacy of the New in Town intervention will be tested in a two-arm randomized controlled trial with a waitlist control group. Social self-efficacy will be the primary outcome. Secondary outcomes will include loneliness, perceived social support, and satisfaction with life. Additionally, we will measure user experience among participants allocated to the experimental group. We aim to recruit a total of N  = 280 participants aged at least 18 years who have changed their place of residence in the last 6 months and have an Internet connection. Participants will be assessed at baseline, 3-week post-test, and 8-week follow-up., Discussion: The trial will provide insights into the efficacy of Internet-based self-help interventions in increasing social self-efficacy. Given that the intervention works, New in Town could provide an easily accessible support option for internal migrants in Poland., Trial Registration: The trial was registered with ClinicalTrials.gov (identifier: NCT04088487) on 11th September 2019., Competing Interests: The authors declare that they have no competing interests., (© 2020 The Authors.)

We have applied the CCSD(T)-F12a/cc-pVTZ-F12//CCSD(T)/cc-pVTZ level of theory to calculate energies for 22 reactions pertinent to the stability and reactivity of hardly isolable cyanoform (HC(CN) 3 ). A number of exothermic processes has been indicated, especially the hydration. In the predicted mechanism for the gas-phase hydration of cyanoform, the H 2 O addition to the C≡N bond corresponds to a rate-limiting step, which is aided by an extra molecule of water. Also, for the cyanoform dihydrate (H 2 NC(OH)C(CN)CONH 2 ) product, the experimentally identified compound, the more stable planar isomer exhibits intramolecular O-H···O═C (not N-H···O═C) H-bonding. Our calculated structures, binding energies, and NBO data for [HC(CN) 3 ] n ( n = 2,4) clusters suggest that the non-conventional C-H···N H-bonds contribute to their stability. Among the surveyed structures of the C≡N group incorporating products of reactions examined, the CCSD(T)/cc-pVTZ molecular parameters of cyanocarbons C 2 (CN) 4 , C 2 (CN) 6 , and C 6 (CN) 6 can be regarded as the most accurate gas-phase values up-to-date.

Palmoplantar pustulosis (PPP) is a chronic inflammatory disease, most often occurring in middle-aged women. In the course of the condition, painful skin lesions appear on the hands and feet, i.e., areas that are extremely important in everyday life. Therefore, the disease significantly reduces quality of life. The pathogenesis of this disease is poorly understood, although it is known that genetic, immunological and environmental factors play a role in its development. Clinical observations confirm the role of nicotine and contact allergens in the development of the lesions. The skin lesions can also occur as a side effect of certain medications. In some cases, PPP coexists with other diseases, i.e., seronegative arthropathies, as well as celiac and thyroid diseases. There is also a connection between the disease and infectious bacterial foci. Exacerbation of the skin lesions is triggered by stress. Therefore, patients require multidirectional tests, since finding the cause of the disease is essential to administering effective treatment.

Protein (un)folding rates depend on the free-energy barrier separating the native and unfolded states and a prefactor term, which sets the timescale for crossing such barrier or folding speed limit. Because extricating these two factors is usually unfeasible, it has been common to assume a constant prefactor and assign all rate variability to the barrier. However, theory and simulations postulate a protein-specific prefactor that contains key mechanistic information. Here, we exploit the special properties of fast-folding proteins to experimentally resolve the folding rate prefactor and investigate how much it varies among structural homologs. We measure the ultrafast (un)folding kinetics of five natural WW domains using nanosecond laser-induced temperature jumps. All five WW domains fold in microseconds, but with a 10-fold difference between fastest and slowest. Interestingly, they all produce biphasic kinetics in which the slower phase corresponds to reequilibration over the small barrier (<3 RT ) and the faster phase to the downhill relaxation of the minor population residing at the barrier top [transition state ensemble (TSE)]. The fast rate recapitulates the 10-fold range, demonstrating that the folding speed limit of even the simplest all-β fold strongly depends on the amino acid sequence. Given this fold's simplicity, the most plausible source for such prefactor differences is the presence of nonnative interactions that stabilize the TSE but need to break up before folding resumes. Our results confirm long-standing theoretical predictions and bring into focus the rate prefactor as an essential element for understanding the mechanisms of folding., Competing Interests: The authors declare no conflict of interest.

Compressed natural gas (CNG) is a widely used automotive fuel in a variety of countries. In case of a vehicle fire where the safety device also malfunctions, a failure of the CNG automotive cylinder could occur. Such a cylinder failure is associated with severe hazards for the surrounding environment. Firstly, a comprehensive analysis is given below, summarizing various accidents involving CNG automotive cylinders and their consequences. In an extensive experimental program, 21 CNG automotive cylinders with no safety device were tested. Of the 21, burst tests were carried out on 5 Type III and 5 Type IV cylinders. Furthermore, fire tests with 8 Type III and 3 Type IV cylinders were conducted. Apart from cylinder pressure, inner temperature and cylinder mantle temperature, the periphery consequences, such as nearfield blast pressure and fragmentation are documented. The maximum measured overpressure due to a Type III cylinder failure was p = 0.41 bar. Each traceable fragment was georeferenced. All-in-all, fragment throw distances of d > 300 m could be observed. As one key result, it can be stated that the tested Type IV CNG cylinders showed less critical failure behavior then the Type III cylinders under fire impingement., (Copyright © 2018 Elsevier B.V. All rights reserved.)