Summary Antibiotic resistance is an increasing threat for public health, underscoring the need for new antibacterial agents. Antimicrobial peptides (AMPs) represent an alternative to classical antibiotics. TAT-RasGAP317-326 is a recently described AMP effective against a broad range of bacteria, but little is known about the conditions that may influence its activity. Using RNA-sequencing and screening of mutant libraries, we show that Escherichia coli and Pseudomonas aeruginosa respond to TAT-RasGAP317-326 by regulating metabolic and stress response pathways, possibly implicating two-component systems. Our results also indicate that bacterial surface properties, in particular integrity of the lipopolysaccharide layer, influence peptide binding and entry. Finally, we found differences between bacterial species with respect to their rate of resistance emergence against this peptide. Our findings provide the basis for future investigation on the mode of action of TAT-RasGAP317-326, which may help developing antimicrobial treatments based on this peptide.
Antimicrobial peptides (AMPs) are molecules with antimicrobial activity and could be a promising alternative to classical antibiotics, whose clinical efficiency is undermined by emergence of resistance. Our group is studying one such antibiotic alternative – the antimicrobial peptide TAT-RasGAP317-326. We recently reported the antimicrobial activity of this peptide against a range of Gram-positive and Gram-negative bacteria. In this article, we show that the presence of divalent cations and low pH levels have an impact on TAT-RasGAP317-326 activity, whereas serum proteins only partially reduce the antibacterial activity of TAT-RasGAP317-326. In addition, we show that iron supplementation reduces TAT-RasGAP317-326 binding to bacteria. Using a transcriptomics approach and screening of bacterial mutant libraries, we map the transcriptional response of bacteria when exposed to TAT-RasGAP317-326 and identify cellular pathways that may play a role in bacterial resistance to TAT-RasGAP317-326. We test combinations of TAT-RasGAP317-326 with other AMPs and detect no evidence for an additive effect between any of the peptide combinations. Finally, we perform a resistance selection screen that reveals differences between bacterial strains with respect to their rate of resistance emergence against the TAT-RasGAP317-326 peptide. Taken together, our findings bring a better understanding of how extracellular factors might impact the antimicrobial activity of TAT-RasGAP317-326 peptide and thus contribute basic biology insight into the mechanisms behind TAT-RasGAP317-326 activity, potentially aiding future strategies to improve the efficiency of this peptide in vivo.
Surf-riding/broaching failure mode is one of the Second Generation Intact Stability Criteria (SGISC) dealt by IMO. The SGISC are structured with a multi-tiered approach: Level 1, Level 2 and Direct Stability Assessment (DSA). When a ship does not verify one level, the next once must be applied, or the ship design must be modified. If ship changes are not feasible, Operational Measures (OM) can be provided to avoid dangerous situations and reduce the likelihood of stability failures. The OM are divided into Operational Limitations (OL) related to areas or routes and related to maximum significant wave heights and Operational Guidance (OG). The surf-riding criterion has been applied on the parent hull of the Systematic Series D, a fast semi-displacement naval hull with forms typically vulnerable to surf-riding phenomenon. The 90 m length ship results vulnerable to Level 1 and 2, therefore Operational Measures have been discussed and provided for a hypothetical route in the Mediterranean Sea (Area 26). Following the OL, in considered Area 26 the ship operations are limited when significant wave heights exceed 3.8 m. The simplified OG define critical ship speeds to be avoided for each considered sea state.
The International Maritime Organization (IMO) finalized the Second Generation Intact Stability Criteria (SGISC), in February 2020. They are intended to be included in Part A of the 2008 International Code on Intact Stability in the following years. The SGISC consider five modes of dynamic stability failure in waves: parametric roll, pure loss of stability, surf-riding/broaching to, dead ship condition and excessive acceleration. In this paper, two semi-displacement, round bilge and transom stern hull forms, the parent hull of the Systematic Series D and the ONR Tumblehome, i.e. typical naval hull forms, are examined. Although naval ships are not directly impacted by SGISC, they are sensitive to dynamic stability failure phenomena due to their geometry and range of service speeds. The procedures to assess the ship vulnerability to the dead ship condition and excessive acceleration criteria, referring to the latest drafts of the criteria (SDC 7/5, 2019), were implemented in Matlab®,. The limiting KG curves associated with this set of criteria were obtained for each vessel. The minimum allowable KG curve associated with the excessive acceleration criterion was compared with the maximum allowable KG curve associated with dead ship condition, to investigate the existence of a safe operational area.
Immersion tests with different stainless steels have been performed, while the pH was stepwise decreased and then increased again. During 8.5‐day exposure, the depassivation and repassivation pH values as a function of pitting resistance equivalent number were determined. There is always a gap between both pH values (depassivation and repassivation), indicating that for every steel, there are conditions where an existing passive layer can be maintained but cannot be rebuilt after depassivation. In such environments, the passive layer is thicker, consisting mainly of molybdenum and iron rich oxides, while chromium is dissolved. Usually, depending on conditions, the passive layer is more chromium‐rich, especially the inner layer. This is relevant, for example, for acidizing jobs in oil and gas industry, proving that repassivation after acidizing will happen promptly, when the pH is increased again.
This paper contains results from ichthyofaunal research of freshwater fish in Bosnia and Herzegovina during 20th and at the beginning of twenty-first century. We found presence of more than 100 parasitic species from different groups in 52 freshwater fish species from Black Sea and Adriatic basins and some breeding ponds. Detected parasites belong to Trematoda – 25 species, Monogenea – 15, Cestoda – 16, Nematoda – 15, Acanthocephala - 11, Oligohymenophorea - 5, Phyllopharyngea - 3, and Copepoda – 2 species. Other detected parasite groups are Kinetoplastea, Trepomonadea, Myxosporea, Myxoza, Ichthyostraca, Clitellata and Bivalvia with one species each. This study shows the necessity of research of complete parasitic fauna of freshwater fish in Bosnia and Herzegovina.
: The main objective of this study was to examine the characteristics and the relationship between walnuts in the Una-Sana Canton based on phenotypic properties. This is the first study of preselection of walnut variability in this area. In this study, we evaluated the phenological and morphological characteristics of 75 selected genotypes during 2014 and 2015. Twenty-four phenotypic traits were monitored throughout 2 years on different sites. The results of the PCA analysis showed a very high heterogeneity of walnut seedlings on the examined sites, from the aspect of observed parameters. A limited number of superior genotypes were found, but individual genotypes with high nut and kernel weight, as well as the colour of the kernel were determined, which would classify them as high-ranked parents in hybridization programs. Certain number of genotypes with high values of traits such as: nut weight, kernel weight and a high percentage of kernel were selected for future studies. Amongst the selected trees, genotype G25 had the highest weight of nuts and kernel, as well as a satisfactory color of the kernel. This genotype could be used as a superior tree for further breeding programs in the future. A highlevel of phenotypic variability in this studyrevealed the existence of a rich genetics pool of nuts variation. The genetic diversity of walnuts obtained from our studies will represent a valuable source of information for breeding programs of Persian walnut in future.
ABSTRACT High-risk human papillomaviruses (HPV) can be present and cooperate with Epstein–Barr virus (EBV) to promote the onset and/or progression of various cancers including cervical, breast, head and neck as well as colorectal. In this investigation, we explored the co-prevalence of high-risk HPV and EBV in 74 breast cancer tissues from Qatari women using polymerase chain reaction. We found that high-risk HPV and EBV are present in 48/74 (65%) and 36/74 (49%) of the cases, respectively. While we noted that the presence of HPV presence is associated with triple-negative breast cancer (TNBC) (p = .008), however, the presence of EBV did not correlate with any breast cancer subgroup. Moreover, our data revealed that high-risk HPV and EBV are co-present in 35/74 (47%) of the samples and their co-presence is significantly associated with tumor grade (p = .04) and tumor stage (p = .04). These data indicate that HPV and EBV are commonly co-present in breast cancer and their association could be linked with a more aggressive tumor phenotype. Thus, further investigations are essential to understand the underlying mechanisms of HPV and EBV cooperation in breast carcinogenesis.
OBJECTIVE Irritable bowel syndrome (IBS) has a high comorbidity with mental disorders. The present paper aims to visualise the interplay between IBS and affect (anxiety and mood) in daily life. Furthermore, this interplay may be different depending on risk factors such as childhood trauma. METHODS Using momentary assessment (Experience Sampling Method), data of 24 individuals diagnosed with both IBS and panic disorder were analysed (15 non-trauma and 9 low-trauma-score patients). Networks were constructed, based on multilevel time-lagged linear regression analysis. Regression coefficients present network connections including three negative affect items (down, irritated, rushed), three positive affect items (happy, enthusiastic, cheerful), three abdominal complaints (abdominal pain, bloating, nausea) and one social item (feeling lonely). Those networks were stratified by levels of childhood trauma based on the Childhood Trauma Questionnaire. RESULTS Connections within the group of mood items and within the group of abdominal complaints were more frequent than between abdominal complaints and mood items. When data were stratified by childhood trauma, networks were different. In addition, node strengths were stronger in low-trauma than in non-trauma, although only one was significantly different (enthusiastic). Overall, there were mainly non-significant connections and a clear pattern was not visible. CONCLUSIONS A time-lagged network provides additional insight in connections between abdominal complaints and affective complaints, in patients with IBS and panic disorder, with different levels of childhood trauma. More research is needed to gain a better understanding of symptom formation and the impact of variation in context on individual symptom experiences in IBS with affective comorbidity. Baseline data of a clinical trial: NCT01551225 (http://www.clinicaltrials.gov).
The world is facing an unprecedented outbreak affecting all aspects of human lives which is caused by the COVID-19 pandemic. Due to the virus novelty, healthcare systems are challenged by a high rate of patients and the shortage of medical products. To address an increased need for essential medical products, national authorities, worldwide, made various legislative concessions. This has led to essential medical products being produced by automotive, textile and other companies from various industries and approved under the emergency use authorizations or legal concessions of national regulatory bodies. This paper presents a narrative commentary of the available documentation on emergency use authorizations and legal concessions for medical products during COVID-19 pandemic. The basis for narrative commentary includes scientific articles published in Web of Science, Scopus, PubMed and Embase databases, official publications of international organizations: Food and Drug Agency (FDA), World Health Organisation (WHO), World Bank and United Nations (UN), and national regulatory agency reports in native languages (English, German, Bosnian, and Croatian) published from November 1, 2019 to May 1, 2020. This paper focuses on three types of essential medical products: mechanical ventilators, personal protective equipment (PPE) and diagnostic tests. Evidence-informed commentary of available data and potential identified risks of emergency use authorizations and legal concessions is presented. It is recognized that now more than ever, raising global awareness and knowledge about the importance of respecting the essential requirements is needed to guarantee the appropriate quality, performance and safety of medical products, especially during outbreak situation, such as the COVID-19 pandemic. Emergency use authorizations for production, import and approval of medical products should be strictly specified and clearly targeted from case to case and should not be general or universal for all medical products, because all of them are associated with different risk level. Presented considerations and experiences should be taken as a guide for all possible future outbreak situations to prevent improvised reactions of national regulatory bodies.
Abstract This paper introduces and compares the various techniques for identification and analysis of low frequency oscillations in a power system. Inter-area electromechanical oscillations are the focus of this paper. After multiresolution decomposition of characteristic signals, physical characteristics of system oscillations in signal components are identified and presented using the Fourier transform, Prony’s method, Matrix Pencil Analysis Method, S-transform, Global Wavelet Spectrum and Hilbert Huang transform (Hilbert Marginal Spectrum) in time-frequency domain representation. The analyses were performed on real frequency signals obtained from FNET/GridEye system during the earthquake that triggered the shutdown of the North Anna Nuclear Generating Station in the east coast of the United States. In addition, according to the obtained results the proposed methods have proven to be reliable for identification of the model parameters of low-frequency oscillation in power systems. The relevant analyses are carried out in MATLAB coding environment.
Crossed fused renal ectopia (CFRE) is a rare congenital abnormality of the urinary tract where the kidneys are fused on one side, while the ureter of the ectopic kidney crosses the midline with the normal entrance in the bladder on the contralateral side. Congenital anomalies are associated with a stone formation whose management represents a real challenge. To our knowledge, we report the second case of CFRE associated with ureteral stone, which has been successfully resolved with Extracorporeal Shockwave Lithotripsy (ESWL) and the first of its kind where a sufficient degree of stone disintegration has been achieved after a single session with a complete stone clearance during the follow-up. Radiological examination showed an inferior type of CFRE with stone in the proximal part of the ureter of the upper kidney. ESWL is an acceptable and effective treatment option in CFRE patients due to the minimally invasive approach, potentially high stone-free rate, and rare complications.
Enabling humans and robots to safely work close to each other deserves careful consideration. With the publication of ISO/TS 15066 directives on this matter, two different strategies, namely the Speed and Separation Monitoring and the Power and Force Limiting, have been proposed. This letter proposes a method to efficiently combine the two aforementioned safety strategies for collaborative robotics operations. By exploiting the combination of the two, it is then possible to achieve higher levels of productivity, while still preserving safety of the human operators. This is achieved by the optimal scaling of the initially prescribed velocity, while preserving the path consistency of the robot trajectory. In a nutshell, the state of motion of each point of the robot is monitored so that at every time instant the robot is able to modulate its speed to eventually come into contact with a body region of the human, consistently with the corresponding biomechanical limit. Validation experiments have been conducted to establish that the proposed method enables substantially less stringent limits on robot performance while still allowing for the safety limits prescribed by ISO directives.
Demographic data suggest a rapid aging trend in the active workforce. The concept of aging at work comes from the urgent requirement to help the aging workforce of the contemporary industries to maintain productivity while achieving a work and private life balance. While there is plenty of research focusing on the aging population, current research activities on policies covering the concept of aging at work are limited and conceptually different. This paper aims to review publications on aging at work, which could lead to the creation of a framework that targets governmental decision-makers, the non-governmental sector, the private sector, and all of those who are responsible for the formulation of policies on aging at work. In August 2019 we searched for peer-reviewed articles in English that were indexed in PubMed, IEEE Xplore, and Springer and published between 2008 and 2019. The keywords included the following phrases: “successful aging at work”, “active aging at work”, “healthy aging at work”, “productive aging at work”, and “older adults at work”. A total of 47,330 publications were found through database searching, and 25,187 publications were screened. Afterwards, 7756 screened publications were excluded from the further analysis, and a total of 17,431 article abstracts were evaluated for inclusion. Finally, further qualitative analysis included 1375 articles, of which about 24 are discussed in this article. The most prominent works suggest policies that encourage life-long learning, and a workforce that comprises both younger and older workers, as well as gradual retirement.
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