Negative Form Research Articles

Unique functions for Notch4 in murine embryonic lymphangiogenesis

In mice, embryonic dermal lymphatic development is well understood and used to study gene functions in lymphangiogenesis. Notch signaling is an evolutionarily conserved pathway that modulates cell fate decisions, which has been shown to both inhibit and promote dermal lymphangiogenesis. Here, we demonstrate distinct roles for Notch4 signaling versus canonical Notch signaling in embryonic dermal lymphangiogenesis. Actively growing embryonic dermal lymphatics expressed NOTCH1, NOTCH4, and DLL4 which correlated with Notch activity. In lymphatic endothelial cells (LECs), DLL4 activation of Notch induced a subset of Notch effectors and lymphatic genes, which were distinctly regulated by Notch1 and Notch4 activation. Treatment of LECs with VEGF-A or VEGF-C upregulated Dll4 transcripts and differentially and temporally regulated the expression of Notch1 and Hes/Hey genes. Mice nullizygous for Notch4 had an increase in the closure of the lymphangiogenic fronts which correlated with reduced vessel caliber in the maturing lymphatic plexus at E14.5 and reduced branching at E16.5. Activation of Notch4 suppressed LEC migration in a wounding assay significantly more than Notch1, suggesting a dominant role for Notch4 in regulating LEC migration. Unlike Notch4 nulls, inhibition of canonical Notch signaling by expressing a dominant negative form of MAML1 (DNMAML) in Prox1+ LECs led to increased lymphatic density consistent with an increase in LEC proliferation, described for the loss of LEC Notch1. Moreover, loss of Notch4 did not affect LEC canonical Notch signaling. Thus, we propose that Notch4 signaling and canonical Notch signaling have distinct functions in the coordination of embryonic dermal lymphangiogenesis.

Curing is caring? Liability reforms, defensive medicine and malpractice litigation in a post-pandemic world

We analyze different scenarios of defensive medicine in a unique game theoretic framework, representing a healing relationship between a physician and a patient. The physician should choose between providing the optimal treatment or an inferior one, which can amount to practicing defensive medicine. The patient should choose whether to litigate or not, if an adverse event occurs. When both agents have no dominant strategy, we obtain four scenarios representing the positive and negative forms of defensive medicine, with or without physician's moral hazard. We find that certain legal parameters can have opposite effects on the probabilities that physicians practice defensive medicine and that patients litigate, depending respectively on the form of defensive medicine and on the presence of moral hazard. This result can explain the ambiguous results, reported in empirical literature, of legal reforms aimed at discouraging defensive medicine and medical malpractice litigation.

Moderation of the Stressor-Strain Process in Interns by Heart Rate Variability Measured With a Wearable and Smartphone App: Within-Subject Design Using Continuous Monitoring.

BackgroundThe emergence of smartphones and wearable sensor technologies enables easy and unobtrusive monitoring of physiological and psychological data related to an individual’s resilience. Heart rate variability (HRV) is a promising biomarker for resilience based on between-subject population studies, but observational studies that apply a within-subject design and use wearable sensors in order to observe HRV in a naturalistic real-life context are needed.ObjectiveThis study aims to explore whether resting HRV and total sleep time (TST) are indicative and predictive of the within-day accumulation of the negative consequences of stress and mental exhaustion. The tested hypotheses are that demands are positively associated with stress and resting HRV buffers against this association, stress is positively associated with mental exhaustion and resting HRV buffers against this association, stress negatively impacts subsequent-night TST, and previous-evening mental exhaustion negatively impacts resting HRV, while previous-night TST buffers against this association.MethodsIn total, 26 interns used consumer-available wearables (Fitbit Charge 2 and Polar H7), a consumer-available smartphone app (Elite HRV), and an ecological momentary assessment smartphone app to collect resilience-related data on resting HRV, TST, and perceived demands, stress, and mental exhaustion on a daily basis for 15 weeks.ResultsMultiple linear regression analysis of within-subject standardized data collected on 2379 unique person-days showed that having a high resting HRV buffered against the positive association between demands and stress (hypothesis 1) and between stress and mental exhaustion (hypothesis 2). Stress did not affect TST (hypothesis 3). Finally, mental exhaustion negatively predicted resting HRV in the subsequent morning but TST did not buffer against this (hypothesis 4).ConclusionsTo our knowledge, this study provides first evidence that having a low within-subject resting HRV may be both indicative and predictive of the short-term accumulation of the negative effects of stress and mental exhaustion, potentially forming a negative feedback loop. If these findings can be replicated and expanded upon in future studies, they may contribute to the development of automated resilience interventions that monitor daily resting HRV and aim to provide users with an early warning signal when a negative feedback loop forms, to prevent the negative impact of stress on long-term health outcomes.

Perceptions of organizational politics: A restricted nonlinearity perspective of its effects on job satisfaction and performance

AbstractThis study examined a restricted nonlinearity perspective of the relationship between perceptions of organizational politics (POPs) and work outcomes (i.e., job satisfaction and job performance), dependent upon the level of employee loyalty. Consistent with prior work, we conceptualized POPs as a demand that can have positive effects on job satisfaction and performance, up to certain levels, before negative effects are observed as levels of POPs continue to increase to more extreme levels. Drawing upon the transactional theory of stress, we then argued that this relationship would hold for more loyal employees. However, we hypothesized that these relationships would take a more linear and negative form for less loyal employees. Data analyses of a sample of 177 financial services employees offered mixed support for our hypotheses, replicating prior work that showed a nonlinear, inverse‐U‐shaped relationship between POPs and job satisfaction, and demonstrating an inverted U‐shaped relationship between POPs and both satisfaction and performance for more loyal employees, but not for less loyal employees. We discuss contributions to theory and research, limitations, directions for future research, and practical implications.

A Community-level Test of General Strain Theory (GST) in Mexico

ABSTRACT This study explores the capacity of GST theory at the community level to explain differences in homicide rates across Mexico City neighborhoods. We find that higher levels of economic deprivation, population size, and organized crime activity, the latter being a source of strain leading to the deterioration of Mexican communities, are positively associated with homicide rates. However, neither crowding, residential mobility, nor Indian speaking population, the latter as a proxy of minority population, behave consistent with the theory. Interestingly, population density is consistently associated with homicide rates; however, in the opposite direction that is theorized. Furthermore, stable and statistically consistent relationships seem to have a negative quadratic functional form with homicide, meaning that the impact of these sources of strain will increase along the homicide rates distribution only up to a certain value.

E2F4-Based Gene Therapy Mitigates the Phenotype of the Alzheimer\u2019s Disease Mouse Model 5xFAD

After decades of unfruitful work, no effective therapies are available for Alzheimer’s disease (AD), likely due to its complex etiology that requires a multifactorial therapeutic approach. We have recently shown using transgenic mice that E2 factor 4 (E2F4), a transcription factor that regulates cell quiescence and tissue homeostasis, and controls gene networks affected in AD, represents a good candidate for a multifactorial targeting of AD. Here we show that the expression of a dominant negative form of human E2F4 (hE2F4DN), unable to become phosphorylated in a Thr-conserved motif known to modulate E2F4 activity, is an effective and safe AD multifactorial therapeutic agent. Neuronal expression of hE2F4DN in homozygous 5xFAD (h5xFAD) mice after systemic administration of an AAV.PHP.B-hSyn1.hE2F4DN vector reduced the production and accumulation of Aβ in the hippocampus, attenuated reactive astrocytosis and microgliosis, abolished neuronal tetraploidization, and prevented cognitive impairment evaluated by Y-maze and Morris water maze, without triggering side effects. This treatment also reversed other alterations observed in h5xFAD mice such as paw-clasping behavior and body weight loss. Our results indicate that E2F4DN-based gene therapy is a promising therapeutic approach against AD.

Linguistic and Cultural Study of the Implicit Negation in Spanish

The article considers the category of negation in Spanish as one of the most important components of its culture. Being a language universal and a fundamental category of any culture, negation realizes a great variety of communicative functions. Their study leads to a better understanding of the communicative behavior of the foreign culture representatives. The article presents different points of view on the nature of negation, by analyzing and summarizing different approaches made by different scientists all over the world to the study of this linguistic phenomenon, thus highlighting two main aspects of investigation of negation: formal (syntactical) and conceptual (communicative). When functional capacity of the category in forming negative meanings within real communicative process is studied, the importance should be given to the cognitive and pragmatic features, irrespective of the set grammar rules of negation. In this connection, the article analyzes those forms of negation which are not expressed grammatically. The author has selected and analyzed a number of speech patterns, conveying negative meanings in the process of communication and the following groups were singled out among them: affirmative exclamation, rhetorical question, ironic response. The author stresses that in spite of being manifested at all levels of the language, the implicit negation does not have any fixed marker of expression and it’s always difficult to differentiate it in the context. However, its profound study will help to understand better the communicative behavior of the foreign-language speaking participants in the dialogical interaction. The article examines the comparative aspects of the negation study at the confluence of Russian and Spanish speaking cultures, spotting the differences in the linguistic world pictures.

Imperative Sentence in “The Guidance iPhone Support Website”

This study attempts to describe imperative sentence in “The Guidance iPhone Support Website”. The aim of this study to investigate the types of imperative sentences and to determine the constituent structure by using tree diagram. The data were collected through library research by reading the e-guidance, note taking and classifying the data based on imperative sentence. The analysis of the data was conducted qualitative method and presented descriptively based on the theory proposed by Quirk et al. (1985) in classifying the types of imperative sentence and the theory proposed by Brown and Miller (1991) is used in analysing the constituent structure by using tree diagram. The method that applied in presenting the result of the analysis was used formal and informal methods. There are two types of imperative sentences found In “The Guidance of iPhone Support Website”, as follows: imperative without subject with a total of 242 or 98,4% and negative imperative with a total of 4 or 1,6%. The constituent structure of imperative sentence is described by tree diagram. The constituent of imperative sentence found in data consists of an omitted subject and negative form.

THE DENIED PREDICATE AND ITS APPEARANCE IN THE NOVEL DEAD AND ALIVE BY THE SERBIAN AUTHOR IVAN ZLATKOVIĆ

This work will be about the denied predicate and its appearance in the novel Dead and Alive by the Serbian author Ivan Zlatkovic. It has been largely acknowledged in semantics that action sentences denote events, but we want to find out what happens when these sentences are denied. Precisely, we will check whether they denote only the states in that case. It is believed that a negative action phrase presents something that did not happen and that they introduce some sort of negative event. For this, we ask the question of whether it is possible that a negative sentence presents action and can denote an event. Some linguists including Kamp and Reyle (1993) believe that the negative sentences do not describe eventualities but denote facts to which a reference point in time normally cannot be assigned. Since negation often implies a pause in the action, whereby the given possibility is negated and points out the absence of it, our goal is to indicate the occurrence of a negated event by which it still can be stated the existence and happening of the certain action with its own temporal referent depending on its pragmatic environment, that is crucial for our interpretation of the given event. The objective of this article is to describe the problem of negated events and the negation of rupture. In this regard, we demonstrate how linguists Saussure (2000), Kamp and Reyle (1993), as well as Amsili and Le Draoulec (1996) approached it. It should be noted that this term negation of rupture (négation de rupture in French) implies the reaction of the subject to the absence of an expected event that takes place outside the habit of the subject or the agent of the sentence (Saussure 2000, 260). We gave the example in affirmative and negative form with the same meaning (Jovan ne s’est pas arrêté au signe du policier- Jovan a continué à sa route au dépit du signe du policier (Jovan didn’t stop his car despite the sign of the police officer). Despite the fact that the positive expression and its negated form point to the same meaning, it is very important to answer how we can determine the temporal discourse referent of negated events.

Phosphorylation of CREB at Serine 142 and 143 Is Essential for Visual Cortex Plasticity.

The transcription factor cAMP response element-binding protein (CREB) is involved in a myriad of cellular functions in the central nervous system. For instance, the role of CREB via phosphorylation at the amino-acid residue Serine (Ser)133 in expressing plasticity-related genes and activity-dependent neuronal plasticity processes has been extensively demonstrated. However, much less is known about the role of CREB phosphorylation at Ser142 and Ser143. Here, we employed a viral vector containing a dominant negative form of CREB, with serine-to-alanine mutations at residue 142 and 143 to specifically block phosphorylation at both sites. We then transfected this vector into primary neurons in vitro or intracortically injected it into mice in vivo, to test whether these phosphorylation events were important for activity-dependent plasticity. We demonstrated by immunohistochemistry of cortical neuronal cultures that the expression of Arc, a known plasticity-related gene, requires triple phosphorylation of CREB at Ser133, Ser142, and Ser143. Moreover, we recorded visually-evoked field potentials in awake mice before and after a 7-d period of monocular deprivation (MD) to show that, in addition to CREB phosphorylation at Ser133, ocular dominance plasticity (ODP) in the visual cortex also requires CREB phosphorylation at Ser142/143. Our findings suggest that Ser142/143 phosphorylation is an additional post-translational modification of CREB that triggers the expression of specific target genes and activity-dependent neuronal plasticity processes.

THE EFFECTIVENESS OF AN ACTIVITY-BASED APPROACH TO TEACHING THE PAST TENSE IN MEDICAL ENGLISH FOR PROFESSIONAL PURPOSES

The present paper explores the methods for effective mastering the past tense relying on an activity-based approach following the Common European Framework of Reference for Languages. The aim of the research is to facilitate the teaching and revising the grammar material on the past simple (indefinite) tense, the past continuous (progressive) tense, and the past perfect tense in the process of training undergraduates, Ph.D. students, academic and clinical teachers at a medical university. The results of the research have been integrated into the 1st edition of “Medical English for Academic Purposes” (2018) and “Medical English for Public Health Purposes” (2021). The authors developed the methodological mechanisms to support courses in professional English at higher medical educational institutions through an activity-based approach, which ensures the effective acquisition of a foreign language, promotes the formation of a linguistic personality capable not only of communicating in all areas, but also of successful integration into the international community. The paper provides a wide range of scaffolding activities and methods: using visuals (graphic organizers, charts, etc.), selecting historically meaningful texts, peer-to-peer talk, strategic pairings, “real-life tasks” and modelling situations, the “fishbowl” model and others. The suggested methodological algorithm is feasible for both oral and written communication, reading and listening comprehension activities, group work, individual and self-directed work in class, as well as for in-class or self-paced learning, depending on the features of the curriculum and students’ English proficiency. The receptive aspect of teaching is represented by read-and-translate exercises, targeted texts describing significant events in the history of medicine, as well as true-false exercises to check students’ comprehension. Meanwhile, the reproductive aspect of teaching covers exercises involving opening the brackets, filling the blanks, as well as creating negative and interrogative forms of verbs. Eventually, the productive aspect of teaching is ensured by a wide range of creative speaking and writing activities and “real-life tasks”, aimed at developing students’ communicative competence in English for Professional Purposes (in-class speaking activities (peer-to-peer talk, class discussion). In addition, collecting family history is yet another pragmatically feasible task to revise and study past tenses. The application of an activity-based approach to teaching the past tenses at a medical university is highly effective to foster essential job-related skills, experience and professional readiness. The authors believe that this, in turn, will promote academic mobility and scientific cooperation, thus contributing to the development of higher medical education in Ukraine, which renders the research relevant.

Ectopic expression of Id1 or Id3 inhibits transcription of the GATA-4 gene in P19CL6 cells under differentiation condition.

Inhibitor of DNA binding (Id) is a dominant negative form of the E-box binding basic-helix-loop-helix (bHLH) transcription factor since it is devoid of the basic region required for DNA binding and forms an inactive hetero dimer with bHLH proteins. The E-box sequence located in the promoter region of the GATA-binding protein 4 (GATA-4) gene is essential for transcriptional activation in P19CL6 cells. These cells differentiate into cardiomyocytes and start to express GATA-4, which further triggers cardiac-specific gene expression. In this study, expression plasmids for Ids tagged with human influenza hemagglutinin (HA)-FLAG were constructed and introduced into P19CL6 cells. The stable clones expressing the recombinant Id proteins (Id1 or Id3) were isolated. The GATA-4 gene expression in these clones under differentiation condition in the presence of 1% dimethyl sulfoxide (DMSO) was repressed, with concomitant abolishment of the transcription of α-myosin heavy chain (α-MHC), which is a component of cardiac myofibrils. Thus, the increased expression of Id protein could affect GATA-4 gene expression and negatively regulate the differentiation of P19CL6 cells.

Ionic Liquid-Based Colloidal Formulations for the Synthesis of Nano-MOFs: Applications in Gas Adsorption and Water Desalination.

Microemulsions (MEs) comprising choline dioctylsulfosuccinate [Cho][AOT], a biobased ionic liquid (IL) surfactant as an emulsifier, (R)-(+)-limonene (RL) as a nonpolar phase, and ethylene glycol (EG)/ethanolammonium formate (EOAF) as an organic solvent/low-viscosity IL polar component were constructed. Spontaneous aggregation of [Cho][AOT] was observed with a negative ΔH form using isothermal titration calorimetry. The aggregates of [Cho][AOT] in RL showed a critical micellar concentration (cmc) of ∼5.49 mM, EG (cmc ∼3.99 mM), and EOAF (cmc ∼1.56 mM), and these are further characterized by various techniques. These novel IL-based MEs have been used as nanoreactors for the sustainable synthesis of uniform nanosized metal-organic frameworks (N-MOFs), such as MIL-53(Al), HKUST-1, UIO-66-NH2, and ZIF-8, with a precise control over size and morphology at room temperature. Characterization of N-MOFs has been performed using scanning electron microscopy, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The synthesized N-MOFs have been used to prepare stable and uniform thin film nanocomposite nanofiltration membranes, suitable for desalination of brackish water with excellent flux (31.8 LMH/bar) and rejection (99.0%) of divalent salts.

A temporal study on subordinate’s response to destructive leadership: voice withdrawal as a conflict coping mechanism

PurposeThe literature on destructive leadership has largely ignored the perspective of the subordinate, especially in terms of conflict coping mechanisms. This study aims to integrate research on destructive leadership and subordinates’ voice behaviour as a conflict coping mechanism. Drawing on the social exchange, conservation of resources and social identity theories, it argues that destructive leadership negatively affects employees’ voice behaviour and that this relationship is moderated by subordinate personality and organization climate.Design/methodology/approachThe proposed model was tested on a sample of 275 professionals working in the banking and insurance sector in India using a temporal research design with data collected in two phases six months apart. Partial least squares structural equation modelling was used for data analysis.FindingsThe results support the main effect relationship between destructive leadership and subordinates’ voice behaviour and the moderation of subordinates’ personality and organizational climate. Temporal analysis indicates that the nature of some relationships changed across the two time periods.Practical implicationsA greater understanding of destructive leader behaviour and resultant coping strategies of subordinates is likely to provide insights for managers facing such situations. The findings of this study will inform the creation of redressal and voice mechanisms in organizations.Originality/valueThis is among the first studies to examine the impact of negative forms of leadership on subordinates’ conflict coping mechanisms using a temporal lag design across two time periods.

High shape-accuracy of surface roughnesses upon nano-moulding with optical elastomers

Nano-imprint and nano-moulding with polymers have quite some history already, but usually, those polymers are not specifically selected to allow for optical applications, where absorption and damping due to volume scattering have to be as small as possible. Defined optical (surface) scattering plates represent one such application, i.e., transparent plates with specific surface roughness morphologies. Typically optical scattering plates are made of glass, and the roughness is produced with a mask-less, self-organizational reactive ion etching (RIE) process. As this technology is relatively expensive, it would be beneficial to replicate such surfaces by imprint or moulding into a polymer. Since the scattering characteristics are not only related to micron-sized but also to nm-sized features on the surface, the right choice of the monomer solution is crucial. Here we use the PDMS-based transparent elastomer Elastosil® RT 601 A/B by Wacker Chemie, Munich, Germany, with very good results. We conduct two nano-moulding steps, the first one making the transition from the master to the negative form, the second one from the negative to the positive form. In the case of such scattering plates, the shape-accuracy can be characterized by the very application for which the plates are intended, i.e., by optical scattering. For other applications, scattering might still be an option for characterization. In our case, the transmissive scattering characteristics of the master, the negative form, and the positive form are nearly identical, which reveals the high accuracy of the nano-moulding process. Moreover, the fact that there are nearly no differences between the scattering characteristics of the negative form on one side and the master or the positive form on the other side is a manifestation of ‘Babinet's principle’. Together with the very good achieved accuracy, this finding allows to confine the process to only one moulding step further on and, thus, to the inverse morphology in the polymer for scattering applications.

Exploration of wall angle and tool rotation on surface roughness in Negative Incremental Forming Process

A significant augmentation in the obsolescence of traditional forming techniques results in the strong requirement of developing an emerging and flexible process to fabricate the user-ready parts in the manufacturing units. Single Point Incremental Forming (SPIF) also known as “negative incremental forming” has shown its viability as a novel and emerging forming method for fabricating the customized and batch-type products of sheet materials to satisfy the need of various potential sectors including medical, automobile, and aerospace. This method directly exempts the involvement of dedicated die-sets and turns into the choice of green manufacturing. The surface quality of fabricated parts can greatly decide the suitability and sustainability of the process in various applications. In the current study, the impact of wall angle and tool rotation have been explored for surface roughness during SPIF. Results revealed that the increase in spindle speed resulted in the decrease of Ra value of formed components. Moreover, the Ra value of formed components was found to decrease by 50 % when the experimental condition was changed from the combination of higher levels of wall angle and “free-to-rotate” condition of spindle speed to the combination of lower levels of wall angle (60°) and a higher level of spindle speed (1500 rpm).

Jiella mangrovi sp. nov., a novel endophytic bacterium isolated from leaf of Rhizophora stylosa.

A Gram-stain negative, non-motile, brilliant yellow and non-spore forming, coccoid- or short rod-shaped bacterium, designated strain KSK16Y-1T, was isolated from surface-sterilised leaf of Rhizophora stylosa collected from Shankou Mangrove Nature Reserve, Guangxi Zhuang Autonomous Region, China. Genome of strain KSK16Y-1T is 4.93Mb with 68.1% DNA G + C content and encoded 4359 predicted proteins, 4 rRNAs, 45 tRNAs and 4 ncRNA. Comparative 16S rRNA gene sequence analysis showed that the strain KSK16Y-1T has 98.1%, 97.9% and 96.9% 16S rRNA gene similarities with Jiella aquimaris JCM 30119T, J. endophytica CBS5Q-3T and J. pacifica 40Bstr34T, respectively. Whole-genome comparisons between strain KSK16Y-1T and J. aquimaris 22II-16-19i, J. endophytica CBS5Q-3T, J. pacifica 40Bstr34T, using average nucleotide identity (ANI) values (< 82.0%) and digital DNA-DNA hybridization (dDDH) values (< 25.1%), confirmed low genome relatedness. Strain KSK16Y-1T grew at 20-30°C (optimum, 30°C), pH 6.0-11.0 (optimum, pH 6.0-7.0) and with 0-10% (w/v) NaCl (optimum, 0-2%). Cell wall contained meso-diaminopimelic acid and the major fatty acid was C18:1ω7c. The polar lipid profile consists of phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, one unknown phospholipid, one unknown aminolipid, one unknown aminophospholipid and four unidentified lipids. The predominant respiratory quinone is ubiquinone-10 (Q-10). The polyphasic characterization indicated that strain KSK16Y-1T represents a novel Jiella species. The name Jiella mangrovi sp. nov., type strain KSK16Y-1T (= CGMCC 1.18745T = JCM 34332T) is proposed.

Способы репрезентации семантики запрета в тувинском языке

Introduction. The article discusses the linguistic manifestation of prohibition semantics in Tuvan, analyzes the grammatical and lexical means of its expression, determines the semantic differences of the prohibition indicators and their functional/stylistic features. Goals. The paper aims to describe the grammatical and lexical means of expressing the semantics of prohibition in modern Tuvan, to analyze their meanings, pragmatic and stylistic functions. Materials and Methods. The study employs the descriptive method, functional/semantic and communicative/pragmatic approaches. The research material was provided by examples from digital sources of Tuvan-language texts available at: http://www.tuvancorpus.ru/. Results. The research of Tuvan language materials confirms the data from typologically different languages that indicators of the negative imperative are stylistically universal transmitters of the prohibitive meaning. Other means of expressing prohibition — besides the negative form of the future tense –бас — are stylistically marked. When it comes to express a prohibition, intonation holds an important place since it interacts with the former’s formal indicators proper, context and communicative situation. The paper identifies several types of prohibition (the prohibitive) that have received grammatical and lexical expressions in the Tuvan language — the regulative, preventive, constative, and corrective. Semantically, a comparatively wider range of prohibition values is possessed by the analytical form Tv-п болбас ― a special grammatical indicator of prohibition expressing the regulative, preventive, and constative. For other grammatical means within this system of indicative indicators, transfer of prohibition values is not a key function of theirs. This is the case of the future negative -бас (regulative, preventive) and the past -ды. The latter conveys a value of the admonitive. The system of lexical and grammatical means of expressing prohibition is distinguished by the lexemes хоржок (preventive), болзун, адыр (corrective) that have no certain part of speech status within the modern language. The prohibition lexeme болзун is a grammaticalization of the verb бол- in the meaning ‘to finish’ for the third imperative. There are two verbs бол- and сокса- that implicitly express prohibition/correction. The considered lexico-grammatical and lexical means of prohibition belong to the colloquial style. The formal style employs a number of special lexemes with the meaning of the regulative formed from the stem хору-. This word-formation nest includes verbs, adjectives, adverbs. The results of the study in the functional/semantic field of prohibition in the Tuvan language shall be demanded in further research on modality in the Turkic and other languages.

Cellular senescence promotes endothelial activation through epigenetic alteration, and consequently accelerates atherosclerosis

Senescent vascular cells are detected in atherosclerotic lesion, and its involvement in the development of atherosclerosis has been revealed; however, whether and the mechanism by which endothelial cell (EC) senescence is causally implicated in atherosclerosis remains unclear. We here investigate a role of EC senescence in atherosclerosis by utilizing EC-specific progeroid mice that overexpress the dominant negative form of telomeric repeat-binding factor 2 under the control of the Tie2 or vascular endothelial cadherin promoter. EC-specific progeria accelerated atherosclerosis in mice with target deletion of ApoE. Mechanistically, senescent ECs were markedly sensitive for inflammation-mediated VCAM-1 induction, leading to enhanced monocyte adhesion. Inhibition of NF-κB signaling abolished the enhanced inflammatory responses in senescent ECs, while NF-κB nuclear translocation in response to TNF-α were similar between young and senescent ECs. We found a higher association of VCAM-1 gene with active histone H3 trimethylated on lysine 4, leading to increased NF-κB accessibility in senescent ECs. Our data revealed that EC cellular senescence causes endothelial hyper-inflammability through epigenetic alteration, which consequently accelerates atherosclerosis. Therefore, EC senescence is a promising therapeutic target for the prevention and/or treatment of atherosclerotic disease in elderly population.

The Anima Archetype in Eugene Ionesco's Hunger and Thirst

The aim of this research is to examine Eugene Ionesco's Hunger and Thirst (1966), employing Carl Jung's (1875–1961) Theory of Archetypes. Particular attention is paid to the dynamics of the Anima (the repressed femininity) archetype throughout the play as the protagonist, Jean, sets off on a journey in search for fulfillment. In the play's three episodes, the anima can be observed, in its positive and negative forms, in every woman, real or imaginary, in Jean's life. In the first episode, it is present, in positive form, in his wife and daughter. It is present in its negative form too: in his maternal aunt and in a woman he sees aflame in a vision in the chimney. Both are associated with feelings of guilt, fear of old age and death, but with his aunt there is an additional element, that of repulsive sexual desires. In the second episode, it is present in its positive form in a woman whom he awaits, but never comes. In the third one, it is present, once more, in his wife and daughter with whom he fails to reunite, failing thus to reunite with his inner anima and ends trapped in an eternal vicious circle of servitude.