Familiar Types Research Articles

Design of PI3K-mTOR Dual Inhibitors for Ovarian Cancer: Are We on the Right Track?

Ovarian cancer is one of the most familiar kinds of gynecological cancer seen in women. Though it is not as familiar as breast cancer, the survival rate for ovarian cancer is very low when compared with breast cancer. Even after being one among the familiar types, to date, there are no proper treatments available for ovarian cancer. All the treatments that are present currently show a high rate of recurrence after the treatment. Therefore, treating this silent killer from the roots is the need of the hour. PI3K/AKT/m- TOR pathway is one of the pathways that get altered during ovarian cancer. Studies are already going on for the inhibition of PI3K and mTOR separately. Efforts have been made to inhibit either PI3K or mTOR separately earlier. However, due to its side effects and resistance to the treatments available, current studies are based on the inhibition of PI3K and mTOR together. Inhibition of PI3K and mTOR simultaneously reduces the chances of negative feedback, thus decreasing the toxicity. This review contains the evolution of PI3K and mTOR drugs that are approved by the FDA and are in the trials for different cancer types, including Ovarian cancer. In this article, how a molecular targeted therapy can be made successful and free from toxicity for treating ovarian cancer is discussed. Therefore, this review paves the way for finding an effective scaffold rather than the clinical part. The scaffold thus selected can be further modified and synthesized in the future as dual PI3K/mTOR inhibitors specifically for OC.

Don’t get it wrong! On understanding and its negative phenomena

This paper studies the epistemic failures to reach understanding in relation to scientific explanations. We make a distinction between genuine understanding and its negative phenomena—lack of understanding and misunderstanding. We define explanatory understanding as inclusive as possible, as the epistemic success that depends on abilities, skills, and correct explanations. This success, we add, is often supplemented by specific positive phenomenology which plays a part in forming epistemic inclinations—tendencies to receive an insight from familiar types of explanations. We define lack of understanding as the epistemic failure that results from a lack of an explanation or from an incorrect one. This can occur due to insufficient abilities and skills, or to fallacious explanatory information. Finally, we characterize misunderstanding by cases where one’s epistemic inclinations do not align with an otherwise correct explanation. We suggest that it leads to potential debates about the explanatory power of different explanatory strategies. We further illustrate this idea with a short meta-philosophical study on the current debates about distinctively mathematical explanations.

The Trouble with Relational Values

This paper questions the conceptual and pragmatic worth of the category of relational values. Combining philosophical reasoning with ethnographic field-work in Wallmapu/Chile, I analyse a variety of ways in which people think about, value and behave toward the land. I thereby demonstrate that relational-ity is inherent to held, instrumental and intrinsic values. This means that there is no meaningful way in which to distinguish relational values from more familiar types of values. Yet, to be able to argue that a distinct class of relational values exists, those who have proposed the term have been compelled to silence or downplay the relational natures of those other values. This has the perverse effect of confining, rather than promoting, relational thinking.

Adaptation at the Syntax-Semantics Interface: Evidence From a Vernacular Structure.

Expanding on psycholinguistic research on linguistic adaptation, the phenomenon whereby speakers change how they comprehend or produce structures as a result of cumulative exposure to less frequent or unfamiliar linguistic structures, this study asked whether speakers can learn semantic and syntactic properties of the American English vernacular negative auxiliary inversion (NAI) structure (e.g., didn't everybody eat, meaning "not everybody ate") during the course of an experiment. Formal theoretical analyses of NAI informed the design of a task in which American English-speaking participants unfamiliar with this structure were exposed to NAI sentences in either semantically ambiguous or unambiguous contexts. Participants rapidly adapted to the interpretive properties of NAI, selecting responses similar to what would be expected of a native speaker after only limited exposure to semantically ambiguous input. On a separate ratings task, participants displayed knowledge of syntactic restrictions on NAI subject type, despite having no previous exposure. We discuss the results in the context of other experimental studies of adaptation and suggest the implementation of top-down strategies via analogy to other familiar structure types as possible explanations for the behaviors observed in this study. The study illustrates the value of integrating insights from formal theoretical research and psycholinguistic methods in research on adaptation and highlights the need for more interdisciplinary and cross-disciplinary work in both experimental and naturalistic contexts to understand this phenomenon.

Problem of plane strain state of two-layer body in dynamic elastic-plastic formulation (Part I)

The design of composite and reinforced or armed materials is a requirement of the modern level of production and life. Many methods of calculation and design of such materials are successfully used. In this article, for the design of composite and reinforced materials, a technique for solving dynamic contact problems in more precise an elastic-plastic mathematical formulation is used. To consider the physical nonlinearity of the deformation process, the method of successive approximations is used, which makes it possible to reduce the nonlinear problem to a solution of the sequences of linear problems. In contrast to the traditional plane strain, when one normal stress is equal to a certain constant value, for a more accurate description of the deformation of the sample, taking into account the possible increase in longitudinal elongation, we present this normal stress as a function that depends on the parameters that describe the bending of a prismatic body that is in a plain strain state. The problem of a plane strain state of a beam made from the composite reinforced double-glazed material is being solved. The reinforced or armed material consists of two layers: the upper (first) thin layer of solid steel and the lower (second) main layer of glass. Glass is a non-crystalline, often transparent amorphous solid, that has widespread practical and technological use in the modern industry. The most familiar types of manufactured glass are "silicate glasses" based on the chemical compound silica (silicon dioxide, or quartz). Glass has high strength and is not affected by the processes of aging of the material, corrosion, and creep. In addition, this material is cheap and widely available. Glass can be strengthened, for example, in a melt quenching process. If the cooling is fast enough (relative to the characteristic crystallization time), then crystallization is prevented, and instead the disordered atomic configuration of the supercooled liquid is frozen into a solid state. This increases the strength properties of the glass. The reinforced composite beam is rigidly linked to an absolutely solid base and on which an absolutely solid impactor acts from above in the centre on a small area of initial contact.

Contraceptive Use and the Associated Factors among Women of Reproductive Age in Jazan City, Saudi Arabia: A Cross-Sectional Survey.

The contraceptive use profile is poorly understood in some Gulf Arabian countries, including Saudi Arabia. The present study aimed to assess the knowledge, attitude, and practices related to contraceptive use among women of childbearing age in Jazan city, Saudi Arabia. An observational, analytical cross-sectional study was conducted among a random sample of 450 women in Jazan city. The data were obtained through personal interviews using a questionnaire that included questions on women's level of knowledge about contraception methods, their attitudes towards contraception methods, and their practices. Data were analyzed using descriptive and inferential statistics techniques using the SPSS program. The prevalence of ever having used contraceptives was significantly different according to age group, job status, children ever born, and the number of pregnancies (p < 0.05 for all). On the other hand, the prevalence of desire to use the contraceptives in the future was high, at 70.9%, with a 95% CI [66.5-74.9]. It differed significantly according to age group and job status (p < 0.05 for both). The most familiar and usable types of contraceptives were pills (36.3%) and intrauterine devices (24.4%). When asked their reasons for using contraceptives, 53.8% of participants cited child spacing and 21.8% improving child health. Logistic regression revealed that the use of contraception among women was more associated with the 20-34 age group [COR = 7.7, 95% CI = 4.4-13.5, p < 0.001] than the 15-24 age group. Having more than one pregnancy and having more than one child were also associated with increased use of contraceptive methods (p < 0.001 for both). These results indicate there is a high level of awareness about contraceptives, a positive attitude toward them, and good practices for the use of them among Saudi women in Jazan. More efforts are needed to improve women's awareness for better utilization of the available services.

Organization of Clinician-Rated Personality Disorder Types According to ICD-11 Severity of Personality Dysfunction.

Objective: The International Classification of Diseases, 11th edition (ICD-11) model of personality disorders (PD) allows clinicians to classify personality dysfunction according to four levels of severity. This approach is partially inspired by Kernberg's levels of personality organization, in which various PD types are organized according to their level of severity. This study sought to investigate whether the established ICD-10 PD categories can be organized according to the four levels of ICD-11 PD severity, and to what extent this organization aligns with Kernberg's four levels of personality organization. Method: A sample of 247 patients were rated by their mental health professionals according to ICD-10 PD categories and ICD-11 PD severity levels. Results: The frequencies of ICD-10 PDs on the different ICD-11 PD severity levels were generally found to be consistent with Kernberg's model. Accordingly, borderline and antisocial PDs predominantly occurred at the most severe levels, whereas anankastic, avoidant, and dependent PDs typically occurred at the milder levels. Only paranoid and histrionic PDs were less consistent with Kernberg's model. Conclusions: The findings indicate that the new ICD-11 PD severity dimension largely aligns with Kernberg's model of personality functioning with respect to the organization of PD types. Clinicians may therefore conceptualize familiar PD types in terms of their ICD-11 PD severity and vice versa.

CUSTOMS AS AN ELEMENT OF ENRICHING THE RURAL TOURIST OFFER - A CHANCE FOR TOURISM DEVELOPMENT AFTER THE CRISIS

Modern tourists are looking for new experiences, i.e. they no longer focus on familiar types of vacation. Rural areas with their material and spiritual heritage can create a product according to the expectations and needs of modern tourists. The 2008 financial crisis and the current health crisis caused by the COVID - 19 pandemic have changed preferences and tourism demand in general. This paper focuses on changes in tourist demand caused by the consequences of the crisis and traditional customs that can be used to differentiate the tourist offer. The initial assumption is that tourists want to escape from urban areas and spend their holidays in rural areas. The results indicate that rural areas have numerous potentials, which, combined with customs, can influence tourists to visit these areas more extensively.

Editors’ Introduction

Editors’ Introduction

Concepts and cognitive structures

ABSTRACT The broad topic of this paper is the relationship between the theoretical notion of a concept and familiar types of cognitive structures (prototypes, exemplars, causal models, etc.) The discussion is organized around different ways that theorists about concepts can attempt to accommodate what has been dubbed the Heterogeneity Hypothesis (roughly: the claim that various types of structures with which concepts have been identified co-exist and form a heterogeneous class). The most general goal of the paper is to clarify the dialectical geography when it comes to different ways of construing the relationship between concepts and familiar cognitive structures. A more focussed and more polemical goal of the paper is to raise problems for so-called pluralist approaches to concepts. This paper will not offer a comprehensive defense of any particular view about the relationship between concepts and cognitive structures, but the discussion will be a convenient venue in which to highlight some virtues of what I will call Higher-Level Unity approaches to concepts.

Soil-atmosphere fluxes of CO2, CH4, and N2O across an experimentally-grown, successional gradient of biocrust community types.

Biological soil crusts (biocrusts) are critical components of dryland and other ecosystems worldwide, and are increasingly recognized as novel model ecosystems from which more general principles of ecology can be elucidated. Biocrusts are often diverse communities, comprised of both eukaryotic and prokaryotic organisms with a range of metabolic lifestyles that enable the fixation of atmospheric carbon and nitrogen. However, how the function of these biocrust communities varies with succession is incompletely characterized, especially in comparison to more familiar terrestrial ecosystem types such as forests. We conducted a greenhouse experiment to investigate how community composition and soil-atmosphere trace gas fluxes of CO2, CH4, and N2O varied from early-successional light cyanobacterial biocrusts to mid-successional dark cyanobacteria biocrusts and late-successional moss-lichen biocrusts and as biocrusts of each successional stage matured. Cover type richness increased as biocrusts developed, and richness was generally highest in the late-successional moss-lichen biocrusts. Microbial community composition varied in relation to successional stage, but microbial diversity did not differ significantly among stages. Net photosynthetic uptake of CO2 by each biocrust type also increased as biocrusts developed but tended to be moderately greater (by up to ≈25%) for the mid-successional dark cyanobacteria biocrusts than the light cyanobacterial biocrusts or the moss-lichen biocrusts. Rates of soil C accumulation were highest for the dark cyanobacteria biocrusts and light cyanobacteria biocrusts, and lowest for the moss-lichen biocrusts and bare soil controls. Biocrust CH4 and N2O fluxes were not consistently distinguishable from the same fluxes measured from bare soil controls; the measured rates were also substantially lower than have been reported in previous biocrust studies. Our experiment, which uniquely used greenhouse-grown biocrusts to manipulate community composition and accelerate biocrust development, shows how biocrust function varies along a dynamic gradient of biocrust successional stages.

Molecular Crosstalk between the Immunological Mechanism of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Oral Cancer.

Oral cancer is a significant non-communicable disease affecting both emergent nations and developed countries. Squamous cell carcinoma of the head and neck represent the eight major familiar cancer types worldwide, accounting for more than 350,000 established cases every year. Oral cancer is one of the most exigent tumors to control and treat. The survival rate of oral cancer is poor due to local invasion along with recurrent lymph node metastasis. The tumor microenvironment contains a different population of cells, such as fibroblasts associated with cancer, immune-infiltrating cells, and other extracellular matrix non-components. Metastasis in a primary site is mainly due to multifaceted progression known as epithelial-to-mesenchymal transition (EMT). For the period of EMT, epithelial cells acquire mesenchymal cell functional and structural characteristics, which lead to cell migration enhancement and promotion of the dissemination of tumor cells. The present review links the tumor microenvironment and the role of EMT in inflammation, transcriptional factors, receptor involvement, microRNA, and other signaling events. It would, in turn, help to better understand the mechanism behind the tumor microenvironment and EMT during oral cancer.

Comparative evaluations of visualization onboarding methods

Comprehending and exploring large and complex data is becoming increasingly important for a diverse population of users in a wide range of application domains. Visualization has proven to be well-suited in supporting this endeavor by tapping into the power of human visual perception. However, non-experts in the field of visual data analysis often have problems with correctly reading and interpreting information from visualization idioms that are new to them. To support novices in learning how to use new digital technologies, the concept of onboarding has been successfully applied in other fields and first approaches also exist in the visualization domain. However, empirical evidence on the effectiveness of such approaches is scarce. Therefore, we conducted three studies with Amazon Mechanical Turk (MTurk) workers and students investigating visualization onboarding at different levels: (1) Firstly, we explored the effect of visualization onboarding, using an interactive step-by-step guide, on user performance for four increasingly complex visualization techniques with time-oriented data: a bar chart, a horizon graph, a change matrix, and a parallel coordinates plot. We performed a between-subject experiment with 596 participants in total. The results showed that there are no significant differences between the answer correctness of the questions with and without onboarding. Particularly, participants commented that for highly familiar visualization types no onboarding is needed. However, for the most unfamiliar visualization type — the parallel coordinates plot — performance improvement can be observed with onboarding. (2) Thus, we performed a second study with MTurk workers and the parallel coordinates plot to assess if there is a difference in user performances on different visualization onboarding types: step-by-step, scrollytelling tutorial, and video tutorial. The study revealed that the video tutorial was ranked as the most positive on average, based on a sentiment analysis, followed by the scrollytelling tutorial and the interactive step-by-step guide. (3) As videos are a traditional method to support users, we decided to use the scrollytelling approach as a less prevalent way and explore it in more detail. Therefore, for our third study, we gathered data towards users’ experience in using the in-situ scrollytelling for the VA tool Netflower. The results of the evaluation with students showed that they preferred scrollytelling over the tutorial integrated in the Netflower landing page. Moreover, for all three studies we explored the effect of task difficulty. In summary, the in-situ scrollytelling approach works well for integrating onboarding in a visualization tool. Additionally, a video tutorial can help to introduce interaction techniques of visualization.

A tale of two MOCs: An adventure fable outlining the constant danger of not following proper process safety protocol

AbstractOne of the process safety management (PSM) concepts that so many have struggled with is management of change. It seems so simple on the surface, but it has resulted in serious incidents. Using a story format, two incidents are recited to illustrate what went wrong with management of change (MOC), and how the incidents could have been avoided. A fairy tale story based on the incidents was created to illustrate the importance of MOC. The fairy tale uses familiar character types and forms to illustrate: why the change was not recognized; hazards of uncontrolled changes; and the importance of MOC in the prevention of process safety incidents. The fairy tale story communicates lessons learned from two incidents that resulted from MOC failures.

Histone Modification on Parathyroid Tumors: A Review of Epigenetics.

Parathyroid tumors are very prevalent conditions among endocrine tumors, being the second most common behind thyroid tumors. Secondary hyperplasia can occur beyond benign and malignant neoplasia in parathyroid glands. Adenomas are the leading cause of hyperparathyroidism, while carcinomas represent less than 1% of the cases. Tumor suppressor gene mutations such as MEN1 and CDC73 were demonstrated to be involved in tumor development in both familiar and sporadic types; however, the epigenetic features of the parathyroid tumors are still a little-explored subject. We present a review of epigenetic mechanisms related to parathyroid tumors, emphasizing advances in histone modification and its perspective of becoming a promising area in parathyroid tumor research.

The Neogrammarian hypothesis and pandemic irregularity*

AbstractAt least three types of sound change (prenasalization of obstruents, lenition of obstruents, conversion of labial consonants to the corresponding labiovelars) are widespread in the Austronesian language family as sporadic innovations. What marks these off as different from more familiar types of irregularity is their repeated occurrence across hundreds of related languages, a phenomenon that can conveniently be called “pandemic irregularity.” All attempts to find an explanation for why pandemic irregularities occur in terms of possibly unrecognized affixation, conditioning, borrowing, or unfinished processes, have proven futile. In particular, it is stressed that pandemic irregularity in sound change is fundamentally different from “lexical diffusion”, and deserves to be recognized in its own right as a process that works against the general application of the regularity hypothesis.

A model of working memory for latent representations.

We propose a mechanistic explanation of how working memories are built and reconstructed from the latent representations of visual knowledge. The proposed model features a variational autoencoder with an architecture that corresponds broadly to the human visual system and an activation-based binding pool of neurons that links latent space activities to tokenized representations. The simulation results revealed that new pictures of familiar types of items can be encoded and retrieved efficiently from higher levels of the visual hierarchy, whereas truly novel patterns are better stored using only early layers. Moreover, a given stimulus in working memory can have multiple codes, which allows representation of visual detail in addition to categorical information. Finally, we validated our model's assumptions by testing a series of predictions against behavioural results obtained from working memory tasks. The model provides a demonstration of how visual knowledge yields compact visual representation for efficient memory encoding.

Reflection of orthographocentrism in dictations as a form of input control

This article is prepared at the intersection of several branches of science, reflecting one of the problems of Russian language teaching techniques through the prism of metalanguage consciousness of the native speakers. The subject of this research is the reflection of the signs of orthographocentrism in dictation as a form of control. The object is dictation as a form of control. The article aims to prove that dictation as a form of input control manifests orthographocentrism as one of the presumptions of metalanguage consciousness of the native speakers. The analysis of dictation results written by the first-year students of non-philological specialty in the beginning of the academic year, once again confirms that this type of control is only the spelling literacy level check of the students, rather than their communicative competencies. The main conclusions are as follows: dictation does not detect the level of formation of communication skills of the school graduates thar are essential for training and effective interaction in society overall. Dictation tests the level of orthographic (and punctuation) literacy. The analysis of dictations indicated that besides the familiar types of errors, they may contain incorrect spellings that are outside the traditional classification methods for teaching the Russian language. Spelling errors should be considered as communicative hindrances within the communication structure, since orthography as the language section can be presented in the communicative aspect. In this regard, the existing classifications of errors can be revised, so are the criteria and evaluation of students' written tests.

Infants' visual exploration strategies for adult and child faces.

By the end of the first year of life, infants' discrimination abilities tune to frequently experienced face groups. Little is known about the exploration strategies adopted to efficiently discriminate frequent, familiar face types. The present eye-tracking study examined the distribution of visual fixations produced by 10-month-old and 4-month-old singletons while learning adult (i.e., familiar) and child (i.e., unfamiliar) White faces. Infants were tested in an infant-controlled visual habituation task, in which post-habituation preference measured successful discrimination. Results confirmed earlier evidence that, without sibling experience, 10-month-olds discriminate only among adult faces. Analyses of gaze movements during habituation showed that infants' fixations were centered in the upper part of the stimuli. The mouth was sampled longer in adult faces than in child faces, while the child eyes were sampled longer and more frequently than the adult eyes. At 10months, but not at 4months, global measures of scanning behavior on the whole face also varied according to face age, as the spatiotemporal distribution of scan paths showed larger within- and between-participants similarity for adult faces than for child faces. Results are discussed with reference to the perceptual narrowing literature, and the influence of age-appropriate developmental tasks on infants' face processing abilities.

Modelling Selectional Super-Flexibility

The selectional flexibility of some attitude verbs (e.g. know, realize, report) between declarative and interrogative complements has been the subject of much recent work in formal semantics. However, little attention has been paid to verbs (e.g. see, remember, observe) that embed an even wider variety of complements (incl. subject-controlled gerundive small clauses and concrete object-denoting DPs). Since the familiar types of some of these complements resist an embedding in the type for questions [= sets of propositions], these verbs challenge Theiler, Roelofsen & Aloni’s (2018) uniform interpretation strategy for the complements of responsive verbs. My paper answers this challenge by uniformly interpreting the different complements of selectionally super-flexible verbs like remember in a generalized type for questions, viz. as parametrized centered questions. It shows that the resulting semantics captures the intuitive entailment pattern of these verbs.