Entry Path Research Articles

Model of Scientific and Methodological Support for Training of Mentors for Vocational Education System in the Conditions of Digitalization

Under the influence of digitalization, pedagogical activity in the system of modern vocational education is complicated and requires the mastering and improvement of competences in the field of design and the creation of a practical-oriented environment for training. Mentoring in such a system is becoming a key element in the training of competitive personnel. In this regard, it is fair to speak of the relevance of teacher training on the basis of the principles of variability and modularity, with the possibility of providing different entry paths, taking into account the availability or lack of experience in pedagogical activities, as well as basic profession and individual needs. The study is based on the use of methods of theoretical analysis, systematization, generalization of scientific and pedagogical literature on the topic of research, modeling. In the course of the study, the significance of the mentor’s psychological and pedagogical competence for vocational education system was shown, the content of its motivational-value, cognitive, process-activity, and reflective-analytical components that determine the effectiveness of the implementation of productive mentoring in the context of digitalization. A structural model of scientific and methodological support for the training of mentors for vocational education system in the context of digitalization is proposed.

Crystallographic and cryogenic electron microscopic structures and enzymatic characterization of sulfur oxygenase reductase from Sulfurisphaera tokodaii

Sulfur oxygenase reductases (SORs) are present in thermophilic and mesophilic archaea and bacteria, and catalyze oxygen-dependent oxygenation and disproportionation of elemental sulfur. SOR has a hollow, spherical homo-24-mer structure and reactions take place at active sites inside the chamber. The crystal structures of SORs from Acidianus species have been reported. However, the states of the active site components (mononuclear iron and cysteines) and the entry and exit paths of the substrate and products are still in dispute. Here, we report the biochemical and structural characterizations of SORs from the thermoacidophilic archaeon Sulfurisphaera tokodaii (StSOR) and present high-resolution structures determined by X-ray crystallography and cryogenic electron microscopy (cryo-EM). The crystal structure of StSOR was determined at 1.73 Å resolution. At the catalytic center, iron is ligated to His86, His90, Glu114, and two water molecules. Three conserved cysteines in the cavity are located 9.5–13 Å from the iron and were observed as free thiol forms. A mutational analysis indicated that the iron and one of the cysteines (Cys31) were essential for both activities. The cryo-EM structure was determined at 2.24 Å resolution using an instrument operating at 200 kV. The two structures determined by different methodologies showed similar main chain traces, but the maps exhibited different features at catalytically important components. A possible role of StSOR in the sulfur metabolism of S. tokodaii (an obligate aerobe) is discussed based on this study. Given the high resolution achieved in this study, StSOR was shown to be a good benchmark sample for cryo-EM.

Prior art for the development of a fourth purification stage in wastewater treatment plant for the elimination of anthropogenic micropollutants-a short-review

<img src="file:///C:/Users/Administrator/Desktop/Doc1.mht" alt="" /><img src="https://www.aimspress.com/fileOther/PIC/environmental/Environ-07-01-005.jpg" alt="" /><br /> The ubiquitous presence of pharmaceuticals in the aquatic environment is a worldwide problem of today. Current analytical methods reveal ever more pharmaceuticals in different water bodies. The concentrations in waters that are detectable reach nano-and picogram ranges, i.e., ppb and ppt levels. Observed concentrations amount to as high as few micrograms. Among the major entry paths are wastewater treatment plants, which are often unable to eliminate the pharmaceuticals sufficiently relying on their three conventional purification stages. Hence, pharmaceuticals enter the aquatic environment without desirable deconstruction. Thus, advanced wastewater treatment processes are under development to retain or eliminate these trace contaminants. According to Decision 2018/840, a watchlist of 15 contaminants of significant interest has been established for the monitoring of surface waters in the European Union. The contaminants include biocides and pharmaceuticals, among them three estrogens, estrone (E1), 17-β-estradiol (E2) and 17-α-ethinylestradiol, (EE2), the antibiotics azithromycin, clarithromycin and erythromycin of macrolide type, ciprofloxacin and amoxicillin of fluoroquinolone and betalactame type. This review will provide an overview of the currently explored and researched methods for the realization of a fourth purification stage in wastewater treatment plants. To this purpose, biological, chemical and physical purification processes are reviewed and their characteristics and potential discussed. The degradation efficacy of the pharmaceuticals on the EU-Watch list will be compared and evaluated with respect to the most promising processes, which might be realized on large scale. Last but not least, recent and novel pilot plants will be presented and discussed.

Structural insights into melatonin receptors.

The long-anticipated high-resolution structures of the human melatonin G protein-coupled receptors MT1 and MT2 , involved in establishing and maintaining circadian rhythm, were obtained in complex with two melatonin analogs and two approved anti-insomnia and antidepression drugs using X-ray free-electron laser serial femtosecond crystallography. The structures shed light on the overall conformation and unusual structural features of melatonin receptors, as well as their ligand binding sites and the melatonergic pharmacophore, thereby providing insights into receptor subtype selectivity. The structures revealed an occluded orthosteric ligand binding site with a membrane-buried channel for ligand entry in both receptors, and an additional putative ligand entry path in MT2 from the extracellular side. This unexpected ligand entry mode contributes to facilitating the high specificity with which melatonin receptors bind their cognate ligand and exclude structurally similar molecules such as serotonin, the biosynthetic precursor of melatonin. Finally, the MT2 structure allowed accurate mapping of type 2 diabetes-related single-nucleotide polymorphisms, where a clustering of residues in helices I and II on the protein-membrane interface was observed which could potentially influence receptor oligomerization. The role of receptor oligomerization is further discussed in light of the differential interaction of MT1 and MT2 with GPR50, a regulatory melatonin coreceptor. The melatonin receptor structures will facilitate design of selective tool compounds to further dissect the specific physiological function of each receptor subtype as well as provide a structural basis for next-generation sleeping aids and other drugs targeting these receptors with higher specificity and fewer side effects.

The Interacted BSc Track at the Sultan Qaboos University: A Phase for Enhancing the Connection Between Research and Academia Among Undergraduate Medical Students

Declining interest in research among medical undergraduate students is of concern. With the expanding mass of medical knowledge all students should be equipped to critically appraise up-to-date information. To address these challenges, an optional intercalated phase was introduced as part of the new medicine doctor (MD) curriculum at the Sultan Qaboos University (SQU). This study aimed to examine the motivating reasons of undergraduate medical students who opted to take the intercalated phase at the College of Medicine and Health Sciences, SQU. To this end, a standardized self-explanatory questionnaire was handed to all students at the first week of enrollment. Over a fiveyear study period, a total of 557 students were eligible to enter the clinical phase of the MD program. Among these students 18 decided to take the intercalated degree, and all agreed to participate in the current study. The mean age of the study cohort was 22 ±1.5 years and fifteen students (83%) were females. Almost half of students took the foundation program before joining the MD entry path, while 45% choose to integrate by their own interest, regardless of career ambitions. The top three most frequent reasons given were to acquire research skills, improve long-term career prospects and a chance to gain publications in journals. Collectively, these findings indicated that the intercalated degree appears to develop a “cluster” of medical undergraduate students who most likely become clinician-academicians capable of taking the scientific discovery from the bench side to the bedside for improving the patient care in Oman.

Assessing prior knowledge of statistics in students attending an online university

This study analyzes the relationship between the entry path to a degree and the prior statistical competence of students taking a Statistics and Probability course at an online university. We assessed students’ prior knowledge by administering a pretest of the information covered in the course analyzed. The sample includes 108 students from different schools of an online university. According to the statistical analysis, students have certain difficulty understanding some concepts related to Probability and Descriptive Statistics, and the entry path affects the students’ understanding of these concepts.

Automatic differentiation between Veress needle events in laparoscopic access using proximally attached audio signal characterization

Abstract The access to the abdomen and the creation of a pneumoperitoneum is an initial and particularly critical step of minimally invasive laparoscopic procedures. Insertion instruments such as the Veress needle need to be introduced blindly into the abdominal cavity, which is associated with inadvertent visceral and vascular injuries. To ensure safe positioning of the instrument, information about the entry path advancement of the tip through the abdominal wall is needed. The main objective of this work is to demonstrate the capability to acquire information about intracorporeal tissuetool interactions of the Veress needle tip, utilizing acoustic emissions recorded at the extracorporeal end of the needle. In an experimental setup, a Veress needle was inserted in a multitissue- layer phantom with a defined insertion speed. Acoustic emissions were recorded with a MEMS microphone attached to the extracorporeal end of the needle. In addition, the counteraction forces during insertion of the needle were measured and a video of the experiment was recorded as reference. With this setup, an audio database of characteristical insertion events was generated. For the classification of characteristic audio events and detection of tissue-layer crossing, features were calculated in the time and frequency domain. Subsequently, a feature dimensionality reduction was performed. The distribution clustering of the audio database in the three-dimensional feature subspace allows a distinction between certain characteristic audio events. The preliminary results show the capability of this acoustic emission based method to detect events related to the insertion of a Veress needle, such as tissue-layer crossing.

Nipah virus persists in the brains of nonhuman primate survivors.

Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes highly lethal henipavirus encephalitis in humans. Survivors develop various neurologic sequelae, including late-onset and relapsing encephalitis, several months up to several years following initial infection. However, the underlying pathology and disease mechanisms of persistent neurologic complications remain unknown. Here, we demonstrate persistent NiV infection in the brains of grivets that survived experimental exposure to NiV. Encephalitis affected the entire brains, with the majority of NiV detected in the neurons and microglia of the brainstems, cerebral cortices, and cerebella. We identified the vascular endothelium in the brain as an initial target of NiV infection during the acute phase of disease, indicating a primary path of entry for NiV into the brain. Notably, we were unable to detect NiV anywhere else except the brains in the examined survivors. Our findings indicate that late-onset and relapsing encephalitis of NiV in human survivors may be due to viral persistence in the brain and shed light on the pathogenesis of chronic henipavirus encephalitis.

Biochemical and structural investigation of taurine:2-oxoglutarate aminotransferase from Bifidobacterium kashiwanohense.

Taurine aminotransferases catalyze the first step in taurine catabolism in many taurine-degrading bacteria and play an important role in bacterial taurine metabolism in the mammalian gut. Here, we report the biochemical and structural characterization of a new taurine:2-oxoglutarate aminotransferase from the human gut bacterium Bifidobacterium kashiwanohense (BkToa). Biochemical assays revealed high specificity of BkToa for 2-oxoglutarate as the amine acceptor. The crystal structure of BkToa in complex with pyridoxal 5'-phosphate (PLP) and glutamate was determined at 2.7 Å resolution. The enzyme forms a homodimer, with each monomer exhibiting a typical type I PLP-enzyme fold and conserved PLP-coordinating residues interacting with the PLP molecule. Two glutamate molecules are bound in sites near the predicted active site and they may occupy a path for substrate entry and product release. Molecular docking reveals a role for active site residues Trp21 and Arg156, conserved in Toa enzymes studied to date, in interacting with the sulfonate group of taurine. Bioinformatics analysis shows that the close homologs of BkToa are also present in other anaerobic gut bacteria.

XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity.

The human MT11 and MT22 melatonin receptors are G protein-coupled receptors (GPCRs) involved in the regulation of circadian rhythm and sleep patterns3. Drug development efforts target both receptors for treatment of insomnia, circadian rhythm and mood disorders, and cancer3, while MT2 has also been implicated in type 2 diabetes (T2D)4,5. Here we report the X-ray Free Electron Laser (XFEL) structures of the human MT2 receptor in complex with agonists 2-phenylmelatonin (2-pmt) and ramelteon6 at resolutions of 2.8 Å and 3.3 Å, respectively, along with two structures of function-related mutants, H2085.46A (superscripts represent the Ballesteros-Weinstein residue numbering nomenclature7) and N862.50D, obtained in complex with 2-pmt. Comparison of the MT2 structures with MT18 reveals that, despite the fact that the orthosteric ligand-binding site residues are conserved, there are notable conformational variations as well as differences in [3H]-melatonin dissociation kinetics that provide new insights into the selectivity between melatonin receptor subtypes. In addition to the membrane-buried lateral ligand entry channel that is also observed in MT1, the MT2 structures reveal a narrow opening towards the solvent in the extracellular part of the receptor. We provide functional and kinetic data supporting a prominent role for the intramembrane ligand entry in both receptors, while simultaneously suggesting the possibility of an extracellular entry path in MT2. Our findings contribute to a molecular understanding of melatonin receptor subtype selectivity and ligand access modes, which are essential for the design of highly selective melatonin tool compounds and therapeutic agents.

Piezo1 Channels Contribute to Flow‐Induced Intracellular Calcium Transients in Mouse Cortical Collecting Duct (CCD)

Within the CCD, an acute increase in tubular fluid flow rate (TFFR) (i) subjects principal (PC) and intercalated (IC) cells therein to biomechanical forces including hydrostatic pressure/circumferential stretch (CS), fluid shear stress (FSS) and drag/torque on PC cilia, and (ii) leads to a biphasic increase in intracellular Ca2+ concentration ([Ca2+]i) characterized by an immediate high amplitude increase to a peak value within ~10 s due to release of IP3‐sensitive internal Ca2+ stores coupled to extracellular Ca2+ entry at the basolateral membrane, followed by a decay to a plateau elevation in [Ca2+]i that exceeds baseline, sustained by luminal Ca2+ entry (Liu et al. AJP Renal Physiology 2003, 2005; 2007). The latter increase in [Ca2+]i is necessary for flow induced K+ secretion (FIKS) in the microperfused mammalian CCD. The identity of the basolateral Ca2+ entry path is unknown. We sought to examine whether Piezo channels, a family of mechanically‐activated Ca2+ permeable channels, contribute to this response. RNAscope detected single Piezo1 RNA molecules in mouse renal cortex. Immunofluorescence studies in mice expressing Piezo1‐tdTomato construct revealed robust basolateral and faint apical Piezo1 localization in both PC and IC. Flow‐induced [Ca2+]i transients, inferred from fluorescence intensity ratios (FIRs), were measured in microperfused mouse CCDs loaded with the Ca2+ indicator fura‐2 and then subject to low or high TFFRs, in the absence or presence of GsMTx4 (piezo‐blocker) or Yoda1 (piezo1‐activator). IC in CCDs from male and female mice preincubated with luminal or bath GsMTx4 (5 μM) failed to exhibit a flow‐induced increase in [Ca2+]i in response to an acute increase in TFFR. Addition of luminal or bath Yoda 1 (1 μM) to CCDs perfused at a low TFFR led to an increase in [Ca2+]i over 90 s in both PC and IC; addition of Yoda1 (10 μM) to the bath further increased [Ca2+]i. We speculate that mechanosensitive Piezo1 channels, expressed on the basolateral&gt;apical membranes of PC and IC in the mouse CCD, contribute to the increase in [Ca2+]i triggered by an increase in TFFR.Support or Funding InformationNIDDK: R01 DK38470, R01 DK51391 and P30 DK079307This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Structural basis of unidirectional export of lipopolysaccharide to the cell surface.

Gram-negative bacteria are surrounded by an inner cytoplasmic membrane and by an outer membrane, which serves as a protective barrier to limit entry of many antibiotics. The distinctive properties of the outer membrane are due to the presence of lipopolysaccharide1. This large glycolipid, which contains numerous sugars, is made in the cytoplasm; a complex of proteins forms a membrane-to-membrane bridge that mediates transport of lipopolysaccharide from the inner membrane to the cell surface1. The inner-membrane components of the protein bridge comprise an ATP-binding cassette transporter that powers transport, but how this transporter ensures unidirectional lipopolysaccharide movement across the bridge to the outer membrane is unknown2. Here we describe two crystal structures of a five-component inner-membrane complex that contains all the proteins required to extract lipopolysaccharide from the membrane and pass it to the protein bridge. Analysis of these structures, combined with biochemical and genetic experiments, identifies the path of lipopolysaccharide entry into the cavity of the transporter and up to the bridge. We also identify a protein gate that must open to allow movement of substrate from the cavity onto the bridge. Lipopolysaccharide entry into the cavity is ATP-independent, but ATP is required for lipopolysaccharide movement past the gate and onto the bridge. Our findings explain how the inner-membrane transport complex controls efficient unidirectional transport of lipopolysaccharide against its concentration gradient.

Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis

SummaryAxon loss determines persistent disability in multiple sclerosis patients. Here, we use in vivo calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels determine the choice between axon loss and survival. We rule out the endoplasmic reticulum, glutamate excitotoxicity, and the reversal of the sodium-calcium exchanger as sources of intra-axonal calcium accumulation and instead identify nanoscale ruptures of the axonal plasma membrane as the critical path of calcium entry.

Interaction of viral pathogen with porin channels on the outer membrane of insect bacterial symbionts mediates their joint transovarial transmission.

Many hemipteran insects that can transmit plant viruses in a persistent and transovarial manner are generally associated with a common obligate bacterial symbiont Sulcia and its β-proteobacterial partner. Rice dwarf virus (RDV), a plant reovirus, can bind to the envelope of Sulcia through direct interaction of the viral minor outer capsid protein P2 with the bacterial outer membrane protein, allowing the virus to exploit the ancient oocyte entry path of Sulcia in rice leafhopper vectors. Here, we show that RDV can hitchhike with both Sulcia and its β-proteobacterial partner Nasuia to ensure their simultaneous transovarial transmission. Interestingly, RDV can move through the outer envelope of Nasuia and reside in the periplasmic space, which is mediated by the specific interaction of the viral major outer capsid protein P8 and the porin channel on the bacterial outer envelope. Nasuia porin-specific antibody efficiently interferes with the binding between RDV and the Nasuia envelope, thus strongly preventing viral transmission to insect offspring. Thus, RDV has evolved different strategies to exploit the ancient oocyte entry paths used by two obligate bacterial symbionts in rice leafhoppers. Our results thus reveal that RDV has formed complex, cooperative interactions with both Sulcia and Nasuia during their joint transovarial transmission. This article is part of the theme issue 'Biotic signalling sheds light on smart pest management'.

Spectroscopy of Oxygen-Sensitive Material for Measuring Contact Lens Oxygen Transmissibility

ABSTRACTPurpose: Oxygen permeability or transmissibility is a crucial parameter for contact lenses to ensure that extended wear will not induce corneal hypoxia. This work tests a new method of using the oxidation of cysteamine, an oxygen-sensitive chemical, to quantify the oxygen transmissibility of current commercial contact lenses and contact lenses loaded with vitamin E.Methods: 3D printing was used to modify eye drop bottles and quartz cuvettes to create systems that allowed insertion of a contact lens in between the cysteamine solution and air. Both systems were exposed to atmospheric conditions where the only path of entry for oxygen was through the contact lens. The entering oxygen reacted with cysteamine, and the rate of cysteamine oxidation was measured using UV-vis spectrophotometry. The rate was then stoichiometrically related to oxygen transmissibility.Results: The eye drop method predicted transmissibility values within 9% of established, commercial values. The cuvette method predicted values within 10% of established values for silicone hydrogel lenses without any correction factor and within 11% for poly-hydroxyethyl-methacrylate lenses after correcting for oxygen entering the system. Incorporation of 20% (w/w) vitamin E into Acuvue® Oasys® lenses did not have a significant impact on the oxygen transmissibility.Conclusions: Both methods presented in this work can reliably measure oxygen transmissibility of contacts lenses or other materials. Further improvements in manufacturing could lead to improved accuracy and reliability, allowing wider use of this method for quantifying the oxygen transport in contact lenses.

Levels, accumulation patterns and retrospective trends of perfluoroalkyl acids (PFAAs) in terrestrial ecosystems over the last three decades

As a result of their ubiquitous presence in the environment perfluoroalkyl acids (PFAAs) have been demonstrated in numerous organisms worldwide, in particular in those of higher trophic levels. The fact that PFAAs have been detected in various human matrices, together with the resultant potential human health risks, knowledge of possible paths of entry and distribution in various ecosystems, is of great importance. In this context pooled samples of terrestrial ecosystems – roe deer liver (n = 141), earthworms (n = 44) as well as leaves from beech and poplar trees (n = 70) – from the year 1989–2015 were obtained from the German Environmental Specimen Bank and examined for the presence of 11 PFAAs for the first time. In addition to determining individual and total PFAA concentrations, temporal trends have been deduced in order to determine the effectiveness of regulatory measures. The highest total mean concentration of PFAAs (sum of the concentrations of the 11 analytes) were 9.9 μg/kg in the roe deer liver samples, followed by earthworm samples with a mean PFAA concentration of 3.5 μg/kg and leaves with a mean total concentration of 2.5 μg/kg. In regard to temporal trends there was a significant reduction of concentrations for perfluorooctane sulfonate, perfluorooctanoic acid, perfluorononanoic acid and perfluorodecanoic acid in roe deer liver from 2003 to 2015, an indication of the effectiveness of regulatory measures. The same is true for the perfluorooctane sulfonate concentrations in earthworms and for perfluorooctanoic acid concentrations in the leaves. In contrast, an increase in perfluorobutanoic acid concentrations was observed from 2003 to 2015 in all three matrices. In summary it must be noted that in spite of the discernible effectiveness of minimization strategies, PFAAs are still detectable in terrestrial matrices and concentrations of other PFAAs as perfluorobutanoic acid appear to be increasing.

Проблемы реализации государственной политики РФ в области построения цифрового общества

Russia has embarked on the path of entry into a single global digital community, taking on international obligations to implement the policy of building a digital society. This occurs through the expansion of the state telecommunications infrastructure used to interact with the population, as well as through the introduction of digital identification and authenticating of citizens. The paradox is that a country with such a policy runs the risk of partial loss of national sovereignty. Despite the existing military potential, domestic forms of interaction through electronic systems are becoming vulnerable, where virtually all information about citizens of Russia, in particular, about military personnel and special services, is contained in a generally accessible form. Such an open policy makes it possible to commit criminal actions, including sabotage, against the state sovereignty of the country and creates a threat to Russia's national security.

Bacterial contamination of catheter tips and blood culture of a veterinary hospital

Hospital infections have a great importance in unique health, especially when one takes into account that the bacteria that cause these infections can be multidrug resistant, an entry path for these microorganisms can be the peripheral venous catheter used, primarily, to maintain the patients hydration. The objective of this work was to detect bacterial contamination and identify the microorganisms involved through blood culture and culture of peripheral venous catheters used by dogs in four different sectors of a Veterinary Hospital. 21 dogs were selected, without differentiation between age or race, and 21 of them had their blood samples collected and 21 samples of catheter tip used by them. The samples were differentiated and identified by biochemical tests and separated into Gram-Negative bacilli, coagulase-negative Staphylococcus spp. and Streptococcus spp. Among the 42 samples, there was no growth in 59.52% (25) of them, in 26.19% (11) of the samples, there was growth of Gram-Negative Bacilli, 11.90% (05) were coagulase-negative Staphylococcus spp., and 2.39% (01) were Streptococcus sp. This work shows that there should be concern about contamination that may be present in catheters or hospital probes that may cause serious infections in animals or humans.

The Development of Safety Performance Functions for Roundabouts in Amman, Jordan

It is now well established that crash occurrences at roadway segments or intersections are associated with a large variety of factors. Safety Performance Functions (SPF) are statistical models developed to predict crash frequencies for various design variables. In Jordan, almost half of all road crashes occur at intersections, mostly in urban areas. There is a significant number of roundabouts throughout Amman which is increasing without evaluating their safety performance. To assess safety benefits of this kind of intersections, transportation professionals need the powerful statistical tool; the SPF. This study aims to develop SPFs for roundabouts in Amman. The models consider the crash frequency, traffic volume and geometric features of all the studied 20 roundabouts. The developed SPFs were statistically significant (R^2 = 0.91) .The findings of the study revealed that crash frequency has a strong relation with the AADT, roundabout entry angle-degrees, entry path radius, splitter radius, pedestrian crossing structure, inscribed diameter, central diameter, circulating width, entry width, number of circle legs. The developed SPFs are evaluated through a comparison with others from developed countries.

Perkütan Koroner Girişim İçin Kullanılan Vasküler Giriş Yoluna İlişkin Teknik Özellikler, Lokal Vasküler Komplikasyonlar ve Hasta Deneyimleri

Perkütan Koroner Girişim İçin Kullanılan Vasküler Giriş Yoluna İlişkin Teknik Özellikler, Lokal Vasküler Komplikasyonlar ve Hasta Deneyimleri