bluuebunny/crossref_metadata_2025 huggingface dataset:
The Attitudes and Perceptions of Saudi EFL Learners Toward Using English Language Learning Mobile Apps for Learning English
Authors: Alluhaydan Hamad Mohammed
Published: July 2024

This study investigated the views of Saudi EFL students toward using English Language Learning Mobile Apps (MELLA) to learn English. A quantitative approach consisting of questionnaires was used to collect data from eighty-nine participants who shared their attitudes and perceptions about MELLAs. Questionnaire items were rated on a Likert scale which ranged from “Strongly Disagree” (1, very low) to “Strongly Agree” (5, very high). Mean Likert scale scores were used to evaluate participants’ responses. The study found that Saudis’ perceptions of MELLA exceeded their attitudes. Moreover, gender differences were found in Saudis’ attitudes toward the use of MELLA. The highest-ranking female attitude mean scores were observed on items related to pronunciation, dictionary, and listening apps while the highest-ranking male attitude mean scores were related to dictionary, listening, and vocabulary apps. Furthermore, the Saudis’ mean score for MELLA perception was higher than the mean score for MELLA attitude. Results also show that females have a higher perception than males. Finally, minor gender differences regarding MELLA perception were also found; the highest female mean scores were based on easiness and flexibility in the use of apps while males highly perceived the convenience of using an app anywhere and at any time as being most important to them.
Modulation of homologous recombination gene activity in breast tumor cells in an in vitro model
Authors: Tsyganov M. M. , Frolova A. A. , Kravtsova E. A. , Tsydenova I. A. , Ibragimova M. K.
Published: July 2024

Introduction. It has been established that the presence of homologous recombination deficiency in a breast tumor is associated with the effectiveness of treatment. But despite the high chemosensitivity of the tumor to DNA-damaging agents, complete pathological responses to treatment are very rare. And this process may be based on a change in the somatic status of BRCA1, that is, a reversion and return of the wild-type allele occurs and the DNA repair function is restored.

Aim. To evaluate changes in the presence of chromosomal aberrations and the expression profile of the main genes of homologous recombination in cell models of breast cancer under the influence of cisplatin and docetaxel.

Materials and methods. The study was conducted on breast cancer tumor cell cultures: MCF-7, MDA-MB-231 and MDA-MB-468. A cell model of drug resistance was obtained for two drugs: cisplatin and docetaxel. RNA and DNA were isolated from cell suspension using the RNeasy Plus Mini Kit and QIAamp DNA Mini Kit (Qiagen, Germany), respectively. The expression level of homologous recombination genes was assessed using reverse transcription polymerase chain reaction. To assess the presence of chromosomal aberrations, microarray analysis was performed on DNA chips.

Results. Restoration of normal copy number for the BRCA1, CDK12, CHEK1 and RAD51D genes in MCF-7 under the influence of cisplatin was shown. For BRCA2 and PALB2, amplifications were detected. A statistically significant increase in the expression of the BRCA1 (p = 0.04), BRCA2 (p = 0.02), PALB2 (p = 0.01) and RAD51D (p = 0.05) genes was also shown. MDAMB-231 shows that all identified loci with deletions, where the BRCA2, BARD1, CHEK2, PALB2 and RAD54L genes are localized, are restored to normal copy number by cisplatin. The appearance of amplifications was registered for BRCA1, BRIP1, FANCL, RAD51B, PARP1. A similar result was shown for docetaxel. An increase in the expression level is typical for the genes BRCA1 (p = 0.02), BRCA2 (p = 0.02), CHEK2 (p = 0.05), FANCL (p = 0.04), PALB2 (p = 0.05), RAD51C (p = 0.02), PARP1 (p = 0.02), which corresponds to the appearance of amplifications. In the MDA-MB-468 cell culture, an increase in the copy number of only the BRCA1 gene is observed. The effect of docetaxel has no effect on this cell culture. The level of BRCA1 expression increases in direct proportion to the duration of drug action.

Conclusion. Thus, the study showed that under the influence of cisplatin, reversion of not only homologous recombination gene mutations, but also other disorders can occur.
Depolymerization of tubulin as the main molecular mechanism of the cytotoxic and antitumor activity of pyrrole-containing heterocyclic compounds
Authors: Galembikova A. R. , Dunaev P. D. , Ivoilova T. V. , Gilyazova A. I. , Galyautdinova A. E. , Mikheeva E. G. , Zykova S. S. , Igidov N. M. , Kopnin P. B. , Boichuk S. V.
Published: July 2024

Introduction. Microtubules are highly dynamic polymers of α, β-tubulin dimers involves in a broad spectrum of the processes, such as intracellular transport and cell proliferation. This makes them an attractive molecular target for anti-cancer therapies. Substances that affect the dynamic state of tubulin microtubules are known as the mitotic poisons that are effectiveand widely used in the chemotherapy of various tumors. Mitotic poisons are able to interfere with polymerization (stabilization) or depolymerization of tubulin, which in turn leads to the arrest of cells in the M-phase (named as a mitotic catastrophe) and their subsequent death via activation of apoptotic mechanisms. However, the effectiveness of MP-based therapies is gradually decreasing over the time due to development of multiple drug resistance mechanisms in cancer cells. Thus, development of novel compounds selectively targeting tubulin and effectively overcoming multiple drugresistance phenotype in cancer is an urgent need in current oncology.

   Aim. To examine the cytotoxic and antitumor activities of several pyrrole-containing heterocyclic compounds (EPC-91, EPC-92 and PCA-93) against cancer cell lines with epithelial and mesenchymal origin, including those with multiple drug resistance phenotype.

   Materials and methods. Studies were performed on parental human cancer cell lines – triple-negative breast cancer HCC1806, gastrointestinal stromal tumor GIST T-1, osteosarcoma SaOS-2, – sensitive to chemotherapy (paclitaxel, doxorubicin) and their resistant sublines (HCC1806 Tx-R, GIST T-1 Tx-R, SaOS-2 Dox-R), as well as on murine colorectal adenocarcinoma cell line Colon-26, exhibiting primary resistance to the aforementioned chemotherapeutic agents.

   Results. The cytotoxic activities of EPC-91 and PCA-93 were due to their abilities to depolymerize tubulin. The results of immunofluorescence microscopy and Western blotting indicated that the compounds disrupt assembly of tubulin microtubules and prevent polymerization of α-tubulin in cancer cells. Inhibition of tubulin polymerizations led to significant increasein number of round-shaped and phospho-histone 3 (e. g. mitotic) cells, followed by their death through apoptosis. PCA-93 also exhibited potent anti-tumor effect against Colon-26 cells due to its anti-proliferative and proapoptotic activities.

   Conclusion. The data shown here illustrates potent cytotoxic activities of EPC-91 and PCA-93 against multiple cancer cell lines in vitro including those with multiple drug resistance phenotype. Similarly, PCA-93 was found to be highly effective against Colon-26 cell in vivo, thereby illustrating the attractive platform for the development of novel pyrrole-based agents exhibiting potent anti-tumor activities.
Genreology in national linguistics: scientific school o f Floriy Batsevych
Authors: Dergach Dmytro ,   Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
Published: July 2024

The article summarizes the ideas of linguistic genreology in the context of the philological interpretation of the genre's nature. It is determined that the linguistic objectivity of its analysis is based on the ideas of communicative studies. In Ukrainian linguistics, they are systematically represented in the researches of the scientific school of F. Batsevych. The thesis is argued that his ideas that are related to the linguistic interpretation of the genre, its characteristics and communicative dominants, take into account, first of all, different forms and formats of intentions. The author's comment is given on their verbalization in dynamically changing variants as peculiar patterns of communicative situations, typed structure fixed by cultural tradition, as well as the fact that they acquire individual characteristics in the process of communication. It also defined that F. Batsevych emphasizes on the tactics of implementing of communicative strategies, which are interpreted as separate genres in micro-contexts. It is summarized that the research ideas of F. Batsevych in Ukrainian linguistics have developed into a consistent tradition, realized in the works of his colleagues. It allows us to talk about the formation and active functioning of an authoritative scientific school of linguistic genreology. It was determined that the concept of linguistic genreology, formed and systematically implemented by F. Batsevych in the author's texts and researches of his followers, generalizes the communicative dominants of the genre, which are based on extralinguistic parameters: social conditioning, typicality of the communicative situation, formal features, functionality, stability and variability. It is argued that F. Batsevych's linguistic ideas of genre analysis are meaningfully correlated with the objectivity of media genreology (in the context of functional parallelism with linguistic genreology). It was determined that its prospects lie in the implementation of methodological syncretism of the analysis of language in the dynamics of social communication and its functions in the media, in the emergence of invariant forms and methods of verbal mass interaction, in the motivated renewal of its stylistics and genre system. And this, in turn, determines the vectors that leadto the perspective of the ideas of neolinguistic research.
Stylistic markers of pejorative vocabulary in Ukrainian-language cartoons
Authors: Babenko Andriy ,   Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
Published: July 2024

The research is focused on the analysis of popular Ukrainian-language cartoons, such as "SpongeBob", "Cars", "Shrek", "The Adventures of Tom and Friends", "Speak Ukrainian", and "The Simpsons". The central goal of the study is to study how pejorative vocabulary in cartoons can influence the formation of children's language skills and their worldview. An important component of our work is the analysis of different types of communication in animation and their potential impact on children's perception through the principles of informatization, imitation and identification with characters. We seek to find out how animation, being not only a means of entertainment, but also an important element of artistic socialization, can shape children's ideas about social norms, stereotypes and roles. Pejorative language, which often goes unnoticed by adults, can have a decisive impact on children's development, contributing to the emergence of aggressive behavior patterns and the formation of negative stereotypes. In the context of our research, special attention is paid to cartoons, the speech of the characters of which contains pejorative vocabulary, which requires an in-depth analysis of their impact on children. In addition, the impact of globalization on the Ukrainian cartoon industry through the import of foreign cartoons, which carry cultural values and norms of behavior, often different from the traditions of the Ukrainian socio-cultural context, is considered. Such cartoons can influence the formation of the worldview of Ukrainian children, not always in a positive way. Therefore, our work also emphasizes the need to create high-quality domestic cartoon content that would correspond to national cultural traditions and values. The purpose of such content should be to promote the positive speech and emotional development of children, as well as to form in them an adequate understanding of social norms and values.
Experience in Using the Transformer Network Architecture to Approximate Agent’s Policy in Reinforcement Learning
Authors: Novikov N.P. , Vinogradov V.I.
Published: July 2024

This paper discusses the basics of the deep reinforcement learning algorithm and the use of neural networks to approximate the agent’s policy. The comparison of using a fully connected neural network and a transformer network in the reinforcement learning algorithm is considered.
Expert Assignment of Fuzzy Strict Orders
Authors: Smerchinskaya S.O. , Yamanaeva R.R.
Published: July 2024

The paper presents a method for interviewing experts for the case of aggregating fuzzy preferences specified through pairwise comparison of alternatives. The possibility of reducing the number of questions asked to experts during a interviewing is shown. Using an example, we analyze the use of a fuzzy transitive closure for a binary relation being created by an expert during a interviewing, and due to this, reducing the number of comparisons.
Analysis and Documentation of Requirements for the Software Package for Conducting Computational Experiments and Numerical Investigation “Flow Tube – Liquid” System of a Coriolis Flow Meter
Authors: Gudkova E.A.
Published: July 2024

Item. This article describes the stages of development of a software package designed to conduct a series of computational experiments on numerical modeling of the “flow tube – liquid” system of a Coriolis flow meter and automation of algorithms for subsequent data processing and visualization. The purpose of this article is to formulate and document the requirements for a software package, and its design based on modern approaches to the development of software products. Methods. The structure of requirements for the software package was developed based on the Software Requirements Specification template adopted in the Rational Unified Process software development methodology, in accordance with the classification of requirements for FURPS+ software systems. Python 3 and the interpreted programming language of the MATLAB environment were used to develop the complex routines. Results. A structure of requirements for the software package has been developed, including functional and non-functional requirements. A software package consisting of three subprograms has been developed, its structure, main components and capabilities are described, and examples of use are demonstrated. Conclusions. The software package solves the problems of automating modeling algorithms, processing and visualizing data obtained as a result of experiments. It can be used in engineering and scientific research related to the analysis of the performance of Coriolis flow meters.
The Use of Images in Teaching Higher Mathematics
Authors: Kulanin Y.D. , Stepanov M.E.
Published: July 2024

The article continues the cycle of methodological developments of authors [1] - [17]. It discusses some problems related to ways to improve the culture of mathematical thinking of mathematics students. The authors rely on the experience of working at the Faculty of Information Technology of MSUPE.
Recognizing Individuals Prone to Spreading Extremist Ideology in Prison
Authors: Bovin B.G. , Kazberov P.N. , Dikopoltsev D.E.
Published: July 2024

The problem of the research is to identify persons potentially capable of spreading violent ideology at the stage of arrival in a penal institution, during the mandatory psychodiagnostic examination of inmates. The aim of the study was to build a probabilistic model for identifying disseminators of extremist-terrorist ideology. The subject of the study was behavioural characteristics and profiles of protective mechanisms of those convicted of extremist-terrorist crimes. The research methods were expert assessment of behavioural characteristics of convicts and the LSI (Life Style Index) test, which allows to determine behavioural and emotional features of an individual based on the defence mechanisms. Comparison of the behavioural characteristics of persons capable, according to the assessment of the staff, of spreading the ideology of violence, largely corresponded to the behavioural characteristics of the functioning of such defence mechanisms as projection, compensation and reactive formation. At the same time, the behavioural characteristics of individuals with a low probability of propagating extremist-terrorist ideology corresponded to the functioning of defence mechanisms: suppression, regression and intellectualisation. Further research is expected to identify the personal characteristics of inmates vulnerable to radicalisation in prison.
Stalking: Forms of Behavior, Typologies, Responsibility in Foreign and Russian Legislation
Authors: Afanasieva I.V. , Afanasyev I.V. , Pimonov V.A.
Published: July 2024

This article, based on comparative legal analysis, reveals the essential characteristics of the process of development of foreign, international, and Russian legislation in terms of countering stalking (persecution). The psychological mechanisms of this behavior are generalized and systematized, typologies of stalkers are presented, as well as the possibilities of using these typologies in the work of law enforcement agencies. The author’s position is substantiated that theoretical studies of stalking in Russia are in their infancy, and domestic theories explaining stalking are underdeveloped compared to other areas of clinical psychology. Consequently, there is a dearth of research on concepts that can guide the formulation of legal norms aimed at effectively countering stalking in Russia. It is substantiated that persecution is an independent type of criminal offense. Based on a study of foreign legislative experience and known typologies of stalkers, a definition of stalking as a crime is given.
The Relationship of Professional Burnout to Early Maladaptive Schemas in Emergency Psychologists
Authors: Mironova O.I. , Kovalevskaia E.A.
Published: July 2024

Professional burnout is a very common syndrome that affects the well-being of people and the work of entire organizations. It is actively studied on various professional samples, especially on representatives of socionomic professions ("human-to-human"). Over the last decade, early maladaptive schemas (EMS) have been found to be associated with burnout. Despite active research, data on both burnout and EMS in extreme psychologists are lacking. The present study was conducted on this particular sample, which is intended to fill the existing gap. Thirty-six extreme psychologists participated in the study, most of the respondents worked in the emergency department or with hospice patients. The full versions of the Maslach Burnout Inventory (MBI) questionnaire adapted by N. Vodopyanova for socionomic professions, as well as J. Young’s questionnaire for early maladaptive schemes in the adaptation of P. Kasyanik and E. Romanova. Using correlation analysis, it was found that most EMS were related to burnout. After analyzing the data obtained during the empirical study, an additional hypothesis, and an alternative set of techniques to test it were proposed. The results of the study may be of practical importance for burnout prevention in psychologists of extreme profile.
Seismic Hazard Assessment in the Southeastern Korean Peninsula for Large Earthquakes in Northern Kyushu, Japan: A 3D Numerical Simulation of Pseudodynamic Rupture Scenarios
Authors: Lee Jaeseok , Rhie Junkee , Cheon Hwa Sung
Published: July 2024

Active fault segments in the Northern Kyushu area are of concern in seismic hazard analysis of the southeastern Korean Peninsula (KP) due to their proximity. In this study, we numerically simulate the peak ground motions at the southeastern KP for Mw 6.7–7.1 earthquake scenarios at five major active fault segments located in northern Kyushu: Kego SouthEastern, Nishiyama OshimaOki, Nishiyama Nishiyama, Kikugawa Central, and Kikugawa Northern fault segments. We conducted fully 3D seismic-wave propagation simulations integrating 3D seismic velocity model and earthquake scenarios generated through pseudodynamic rupture modeling. After applying the region-specific attenuation value, the predicted peak ground velocities (PGVs) ranged from 0.18 cm/s (modified Mercalli intensity [MMI] III) to 26.76 cm/s (MMI VIII), depending on the earthquake scenarios. The PGV distributions were influenced by several factors, such as crustal velocity anomalies, rupture directivity, and the distribution of source parameters on the fault plane. Despite the fixed fault geometries, magnitudes, and hypocenters, significant variations in peak ground-motion distributions were simulated due to differences in the source statistics. The estimated probability density distributions of PGV indicated a significant likelihood of peak ground motions surpassing 20 cm/s in the Yeongnam Province. Furthermore, we identify a linear relationship between the average PGV values and standard deviation across 20 scenarios for each fault segment, to quantify the uncertainty in the PGV distributions.
Antisocial personality and the therapeutic alliance
Authors:   , Gerstley Linda Jean
Published: July 2024

This research explored the extent to which antisocial addicts' assessments of the therapeutic alliance were correlated with similar assessments made by their drug counselors and psychotherapists and then examined the association between these assessments and treatment outcome at seven months. The assessments of the therapeutic alliance were made at one month into the treatment process using Helping Alliance Questionnaires (Alexander and Luborsky, 1984). Six outcome measures were used. These included five composite scores derived from the Addiction Severity Index (McLellan et al., 1985) which provide ratings of patient status in the following areas: (1) Drug usage; (2) Alcohol usage; (3) Legal status; (4) Employment status and; (5) Medical status. The SCL-90 was used as a measure of psychiatric symptomatology. The first phase of this research examined intercorrelations among the patients', therapists' and counselors' assessments of relationship quality. Counselors and therapists did not agree in terms of their assessments of the quality of their relationships with the same patient although the antisocial addicts showed some similarity in terms of the ways that they assessed their relationships with both their counselors and therapists. The strongest agreement was seen in the assessments made by partners in the dyadic counselor-patient and therapist-patient relationships. The extent to which each of the assessments of the therapeutic alliance were correlated with treatment outcome was addressed. Neither the counselors' assessment nor the patients' assessments of their relationship with their counselor were related to overall outcome. However, positive assessments of the therapeutic alliance made by either the patient or his therapist were associated with a positive overall outcome. Although neither of these assessments were correlated with reduced psychiatric symptomatology, both were found to be related to improved employment status. A positive assessment of the therapeutic alliance made by the patient also was associated with reduced drug usage at seven months. The finding of a positive association between both the patient's and therapist's assessment of the therapeutic alliance and improved functioning lends support to the idea that there are some addicts who meet the DSM-III criteria for Antisocial Personality Disorder who are capable of forming a meaningful relationship with a therapist; and, in turn, are able to benefit from psychotherapy. (Abstract shortened with permission of author.).
Family members and significant others of drug abusers
Authors:   , Garvey Kerry A. , Nezu Arthur M.
Published: July 2024

Given the prevalence of drug abuse in society, family members of drug users are inevitably impacted, yet they have been infrequently studied. The first purpose of this study was to provide an understanding of the family members and significant others (FSOs') who sought unilateral treatment in terms of: (a) selected characteristics of their relationship with the drug user (i.e., levels of satisfaction, cohesion, interpersonal power, interpersonal dependency, and enmeshment); and (b) their psychological distress and personality characteristics. The second, and main, purpose of the study was to examine whether the aforementioned relationship characteristics could predict: (a) the FSOs' treatment tenure; and (b) the FSOs' levels of global distress, depression, and anxiety post-treatment. Sixty-six participants completed the intake evaluation and were referred to 10 weeks of Nar-Anon, the unilateral intervention used in this investigation. Results from descriptive analyses indicated that FSOs reported below-average levels of satisfaction, and general feelings that they lacked interpersonal power/influence with the drug user. However, FSOs reported average levels of cohesion, interpersonal dependency, and enmeshment within the relationship. In terms of psychological distress, FSOs reported symptoms comparable with outpatient mental health populations. However, the FSOs, on average, were less likely to meet criteria for personality disorders than outpatient mental health populations. Results from multiple regression analyses indicated that none of the predicting variables were significantly related to the FSOs' treatment tenure. However, the FSOs' levels of interpersonal dependency were significantly predictive of post-treatment depression and anxiety. Secondary analyses indicated that partners reported significantly higher levels of interpersonal dependency than did parents. Exploratory analyses indicated that FSOs who lived with the drug user were more likely to attend more treatment sessions and to report higher levels on all distress variables post-treatment compared to FSOs who did not live with the drug user. The clinical implications, limitations of this investigation, and directions for future research are discussed.
The effects of knowledge of performance and cognitive strategies on motor skill learning in children with cerebral palsy
Authors:   , Thorpe Deborah Ellen , Valvano Joanne
Published: July 2024

Physical therapists should facilitate skill acquisition, retention and transfer by acknowledging the contribution of cognition to these processes. Cueing children with cerebral palsy to use cognitive strategies to help organize augmented information provided during practice of motor tasks, should enhance the effects of the augmented information, resulting in improvements in learning. The purposes of this study were to determine if, (a) providing knowledge of performance (KP) during practice of a novel motor task, was more effective in improving performance of the task than providing no KP during practice and (b) providing a cognitive strategy (CS) to enhance cognitive operations on KP during practice of a novel motor task was more effective in improving performance of the task than providing KP alone during practice. Thirteen children with a diagnosis of cerebral palsy (CP) between the ages of 6.0 and 12.7 years were assigned randomly to one of three experimental protocols. A single-subject, interactive, nonconcurrent multiple baseline design was utilized. Each subject performed thirty-six, 10 second trials on three days within a five day period, attempting to mobilize in a backward direction on a Pedalo, a therapeutic exercise apparatus. Baselines were of varying lengths and subjects received KP and KP + CS according to designated intervention protocols. Procedural fidelity was established and remained consistently high throughout the study, with mean percent agreement ranging from 86.7-100% for all subjects. A block of four retention trials was performed on the third test day. Videotaped data of backward displacement of the Pedalo were collected for each trial. Visual inspection of the data suggested variability in performance. Visual inspection of the data suggested that practice positively affected performance in all subjects. This was supported by mean scores over phases. Additional analysis of the data utilizing the C statistic and the celeration line, revealed that KP alone made a significant positive difference in performance for only one of the thirteen subjects. KP + CS made a significant positive difference over KP alone in four of the thirteen subjects. Receiving the KP + CS earlier in practice did not contribute to better retention overall. This study suggests that practice does improve motor performance in children with CP. Some children with cerebral palsy can benefit from the use of cognitive strategies during practice of motor tasks. Future research should address learning styles of children with CP, the nature of the information contained in the cognitive strategies, and further analyze the effects of personal constraints on movement tasks in order to better develop efficacious strategies.
Modeling for mechanical behavior of thin films
Authors:   , Zhao Fuzhang , Lau Alan Chun Woon
Published: July 2024

Two integrated computational-experimental methods capable of characterizing nonlinear stress-strain behavior of thin films or coatings are presented. The first method combines Finite Element simulation with Micro-Plane-Strain Compression experimental data for automotive paints (FE-MPSC) to self-consistently characterize the deformation resistance of thin films. A microscopic plane-strain compression apparatus constructed in DuPont Marshall R & D Laboratory by micro-fabrication technology was used to measure the force-displacement relationship of the thin film. Starting with an initial approximation of stress-strain curve assuming a uniform deformation field in the film, the correct stress-strain relationship of the film corresponding to the actual deformation field can be determined by iterative updating in the finite-element simulation. This method can circumvent the over-estimation of uniaxial stress-strain curve based on traditional methods which assume uniform deformation, uniform contact stress profile and ignore the effect of hydrostatic pressure. The second method, similarly, combines Finite Element simulation with Continuous Spherical Indentation experimental data (FE-CSI) to self-consistently characterize the deformation resistance of thin films. FE-CSI method has been applied to both macro-spherical indentation of SAE4340 steel disk and micro-spherical indentation of silicon thin film. Germane features are discussed, concluding remarks are drawn, and future research works are recommended.
Angiogenesis, ovarian cancer and vascular endothelial growth factor
Authors:   , Hazelton Darcie A. , Ruggeri Bruce A.
Published: July 2024

Angiogenesis, the formation of new capillaries from preexisting blood essels, plays an important role in the growth and progression of malignancies. This concept is particularly applicable to ovarian cancer, the growth of which is not sustainable without a concurrent increase in blood supply. We hypothesize that high expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, correlates with ovarian malignancy. We further postulate that VEGF may stimulate angiogenesis in ovarian cancer, thereby promoting the growth and metastatic spread of this neoplasm. Enzyme-linked immunosorbent assay (ELISA) was used to measure VEGF in the cyst fluid of patients with ovarian cancer (n = 13), benign cysts and cystadenomas (n = 23), borderline tumors (n = 5) and functional cysts (n = 8). VEGF levels were markedly elevated in the fluid of malignant cysts (38.5 [special characters omitted] 8.2ng/ml) as compared to benign (1.6 [special characters omitted] 0.4ng/ml, p < 0.001), borderline (5.7 [special characters omitted] 1.5ng/ml, p < 0.001) or functional cysts (3.8 [special characters omitted] 2.0ng/ml, p < 0.001). Follow-up of patients with malignant and borderline lesions demonstrated a correlation between VEGF levels in cyst fluid and tumor recurrence (p < 0.03). Microvascular density of archival malignant ovarian tumors was three times higher (x = 29.6 [special characters omitted] 7.0, p < 0.02, n = 8) than that of benign lesions (x = 11.4 [special characters omitted] 1.8, n = 9). The cyst fluid from five patients with malignancies substantially stimulated the proliferation of human microvascular endothelial cells (x = 63.2 x 104 [special characters omitted] 7.2) as compared to the benign fluid (24.9 x 104 [special characters omitted] 4.6, p < 0.01, n = 4) or control growth medium (x = 26.4 x 104 [special characters omitted] 2.0, p < 0.01). VEGF RNA expression in twelve ovarian cancer cell lines ranged from undetectable to intense signal. ELISA of the conditioned media from six selected cell lines and Western analysis of cellular extracts confirmed the presence of VEGF protein. Actinomycin D experiments indicated that stabilization of VEGF mRNA occurred in cell line A2780. Conditioned medium from cell line SKOV-3 stimulated microvessel outgrowth in a dose-dependent manner in an in vitro model of angiogenesis. Conditioned medium from six cell lines stimulated vessel outgrowth to varying degrees, with A2780 producing the greatest response. These results support the idea that angiogenesis and VEGF are integrally involved in ovarian cancer pathology. They also indicate that ovarian cancers may exhibit heterogenous phenotypes with respect to VEGF expression and angiogenic activity.
The developmental vulnerability of the adoptive child and family within a closed system of adoption
Authors:   , Koenig Mary Ann
Published: July 2024

This dissertation explores the developmental vulnerability of the adoptive child and family within a closed system of adoption. The closed system of adoption permanently severs all ties between birth parents and child, seals all records, and gives little to no information about birth parents. It is the hypothesis of this dissertation that a closed system of adoption engenders denial, increased fantasy, extreme images of good and bad, and loyalty conflicts in the adoptee and adoptive family. Further, it is hypothesized that the search for ones biological parents can be an important step in understanding and resolving the difficulties that a closed system of adoption fosters.
Hypoxia/HIF-1 regulation of mammary morphogenesis and oncogenesis
Authors:   , Whelan Kelly A. , Reginato Mauricio J
Published: July 2024

Epithelial attachment to substratum is critical for survival as cells that do not establish proper adhesion undergo apoptosis. Detachment-induced cell death, termed anoikis, is a fundamental regulator of mammary tissue architecture. Moreover, anoikis resistance is a common feature of cancer cells that has been linked to the disruption of tissue organization associated with breast cancer progression. Premalignant breast cancer lesions such as ductal carcinoma in situ (DCIS), characterized by the presence of cells in ductal lumens, often display hypoxic marker expression. Hypoxia, a common feature of solid tumors, has been linked to tumor-promoting cellular programs including survival, migration and invasion; however, the contribution of hypoxia to cancer-associated morphological alterations has yet to be explored. Here, using a three dimensional (3D) tissue culture model of mammary morphogenesis, we find that hypoxia promotes formation of filled, disorganized acini reminiscent of DCIS-like phenotypes found in vivo. We demonstrate that induction of the pro-anoikis proteins Bim and Bmf during detachment is inhibited by hypoxia. We find that hypoxia-mediated anoikis suppression is dependent upon maintenance of MAPK signaling and the hypoxia-inducible transcription factor HIF-1. Further, hypoxia-mediated acinar disorganization, MAPK signaling and anoikis suppression are sustained after reoxygenation. These data support a model wherein hypoxia, via HIF-1, alters anoikis-associated signaling, allowing epithelial cell survival in the absence of matrix adhesion and potentially contributing to development of early breast cancer lesions. The oncogene ErbB2 is commonly overexpressed breast cancer and can stabilize HIF-1[alpha] expression in a hypoxia-independent manner. Like hypoxia, ErbB2 promotes anoikis resistance through MAPK maintenance and suppression of Bim. To extend our studies, we investigated the role of HIF-1 in ErbB2-mediated anoikis resistance. We find that depletion of HIF-1 in ErbB2-overexpressing cells inhibits anchorage-independence, 3D growth and MAPK and Akt signaling. HIF-1-depleted ErbB2-overexpressing cells also display restoration of anoikis sensitivity that correlates with Bim accumulation and induction of oxidative stress. We propose HIF-1 stabilization as a novel means through which ErbB2 can co-opt signaling pathways associated with hypoxia-mediated survival to establish anoikis resistance. Collectively, these studies define a role for HIF-1 in regulating detachment-induced cell death and tissue architecture in the context of breast carcinogenesis.
Interactions between HIV-1 and host cell RNAi pathways and the characterization of a conditional promoter for use in RNAi-based anti-HIV-1 therapeutics
Authors:   , Sanghvi Viraj R. , Steel Laura F
Published: July 2024

RNA interference is an evolutionarily conserved mechanism of gene regulation with a role in antiviral defense in invertebrates. It has been of interest to discover whether it serves a similar antiviral function in vertebrates. Considerable evidence indicates that RNAi serves an antiviral role during HIV-1 infections and, in turn, HIV-1 has evolved strategies to suppress the silencing machinery. HIV-1 was initially proposed to accomplish this by utilizing the viral products, Tat and TAR, to inhibit the miRNA processing activity of Dicer and to sequester the Dicer co-factor, TRBP, respectively. However, these findings have been controversial and we have re-examined this potentially important interaction. Our results support and extend the conclusion that Tat does not reduce the silencing capacity of cells. Similarly, we find no suppression of silencing pathways in cells with replicating virus, suggesting that viral products such as the TAR element do not reduce the efficacy of silencing. TRBP is of particular interest with regard to HIV-1 replication and RNAi. In addition to its role as a co-factor for Dicer in miRNA processing, it binds with high affinity to the HIV-1 TAR element and can increase the efficiency of expression of HIV-1 gene products. While multiple mechanisms explaining the role of TRBP in HIV-1 replication have been proposed, our data show that TRBP promotes HIV-1 primarily by averting the PKR-mediated antiviral immunity. Moreover, the effect of TRBP on HIV-1 replication is independent of its role in the RNAi pathway. Additionally, we have characterized a chimeric promoter, consisting of a chicken [beta]-actin core promoter fused to the viral TAR element, for the conditional expression of interfering RNAs against HIV-1 for use in the development of antiviral therapeutics. This hybrid CK-TAR promoter can induce potent levels of silencing in response to Tat produced from co-transfected plasmids or during viral replication. Furthermore, compared to the Tat-dependent HIV-1 LTR, it is less responsive to extracellular stimuli including LPS, TNF[alpha], and PMA. The Tat-inducible CK-TAR promoter is an alternative to the LTR that can minimize the risk of vector mobilization and can drive polycistronic expression of interfering RNAs.
The Role of Ferritin Heavy Chain and Opiates in neuroAIDS
Authors:   , Pitcher Jonathan , Meucci Olimpia
Published: July 2024

HIV progression and HIV-associated neurocognitive disorders (HAND) are directly and indirectly exacerbated by substances of abuse, including opiates. The mechanisms by which opiates aggravate HIV and HAND are complex and not well defined. One critical factor in the neuropathogenesis of HIV relates to the interaction between opioid receptors and the HIV co-receptor, CXCR4, which is abundantly expressed in both the immune and nervous system. Importantly, CXCR4 and its natural ligand (the chemokine CXCL12/SDF-1) are involved in fundamental neuronal and glia functions, including neurotransmission, cell differentiation, and survival. Our previous studies in murine models have shown that prolonged morphine treatment down-regulates CXCR4 function due to increased levels of a novel regulator of CXCR4, the ubiquitous iron binding protein Ferritin Heavy Chain (FHC), and that this protein mediates the effect of morphine on CXCR4 both in vitro and in vivo. These data suggest that alterations of CXCR4 function induced by opiates may contribute to HIV ieuropathology, via regulation of FHC. To further test this hypothesis and evaluate potential clinical implications, we measured protein expression of FHC, CXCR4 and pCXCR4 (Ser339 - as indication of receptor status) within brain tissue samples from control subjects, illicit drug abusers (including opiate users), and HIV+ patients by multispectral immunohistological image analysis. Our results demonstrate elevated FHC protein and decreased pCXCR4 expression within digitally isolated cortical neurons of patients with a history of drug use or HIV. Additionally, we studied non-human primates (NHPs) treated with morphine, SIV or both. Importantly, we found consistent results between the human and NHP cohorts suggesting that opiates or HIV/SIV alone are sufficient to induce neuronal FHC expression in vivo and that this is associated with disruption of CXCL12/CXCR4 signaling. Furthermore, preliminary analyses on both human and NHP cohorts suggest neuronal FHC expression is associated with disease progression and neurocognitive impairment.
Development of a Persuasive video Game to Enhance player understanding of Schizophrenia
Authors:   , Alabi Teslim , Wagner Michael G.
Published: July 2024

This thesis primarily investigates the potential of a persuasive video game in educating persons about Schizophrenia. Within this context persuasive games provide an opportunity to encourage attitudinal changes by informing players about the difficulties of coping with Schizophrenia using procedural rhetoric - the formation of arguments through in-game processes expressed through role-playing. In this study, we shall create a persuasive game and examine the effects of game-play on negative attifudes of players. After exposure to the intervention, a posttest questionnaire will be administered to evaluate player's perceptions of Schizophrenia particularly noting if any changes in attitudes or gains in knowledge were evident after playing the game. This study will provide insight on how new media usage; in this case, games, can be used to reinforce positive outcomes, exploiting the potential for learning and persuasiveness of play. In this study, considering the scope we review current interactive anti-stigma simulations, identify their shortcomings and explore how they may be enhanced using persuasive games to improve their effectiveness, to make the experiences more compelling and more accessible to a wider audience.
Using an in vitro model of the polarized cervicovaginal epithelium to investigate the immunomodulatory effects of human semen and impact on the risk of human immunodeficiency virus 1 (HIV-1) transmission
Authors:   , Keogan Shawn , Krebs Fred C
Published: July 2024

Factors in seminal fluid (SF) that have integral roles in reproductive biology may alter the ability of the human immunodeficiency virus type 1 (HIV-1) to penetrate the cervicovaginal epithelium and infect target immune cells. We hypothesized that the consequences of SF exposure would be (i) direct alterations in cervicovaginal epithelial tissue tight junction integrity, resulting in changes in epithelial barrier function with respect to HIV-1 passage, and (ii) polarized release of specific immunomodulatory factors by the epithelium that will modulate the local immune response. To address this possibility, human cell lines derived from three different regions of the female reproductive tract - vagina, ectocervix, and endocervix - were cultured in a transwell cell culture system to model the polarized cervicovaginal epithelial barrier. These polarized monolayers were then exposed apically to SF from healthy donors. Changes in barrier integrity were measured over time by monitoring transepithelial electrical resistance (TEER) and permeability, while protein expression in conditioned media was quantified using a multiplex bead-based immunoassay (Luminex). Apical exposure to SF caused a rapid increase in epithelial integrity across all cell lines by 30 min post-exposure, and a sustained peak in TEER by 3-4 h that persisted for approximately 48 h post-exposure. Epithelial TEER responses to SF and whole semen were similar, indicating that sperm cells did not contribute to this effect. Additional studies demonstrated that a combination of calcium, lipids, and heat labile proteins in SF were responsible for the observed changes in resistance. Measurements of immunomodulatory factors secreted by epithelial cell monolayers after SF exposure demonstrated that factor release varied in a cell-type and time-dependent manner. Considerable cell type-dependent differences were also noted. In preliminary experiments using a HIV-1-responsive reporter cell line, SF exposure also resulted in a reduction in HIV-1 long terminal repeat (LTR) activity, suggesting that SF may reduce the risk of HIV-1 infection during virus transmission. Ongoing studies are investigating changes in epithelial permeability to HIV-1 following SF exposure, the mechanism(s) by which SF affects epithelial cell tight junction integrity, and the downstream effects of epithelium-derived immunomodulatory factors on immune cell recruitment, activation, differentiation, and susceptibility to HIV-1 infection.
Religious orientation and distress
Authors:   , Scott Sarah Brooke , Nezu Christine M.
Published: July 2024

The relationship between religious orientation and level of distress among adult cancer patients was explored. The primary hypothesis was that a significant relationship between religious orientation and level of distress would be found. Further, this relationship would be mediated by problem orientation. Additionally, the relationship between religious orientation and problem orientation was also investigated. Ninety-three participants for this study were recruited to complete five questionnaires that assessed the constructs of interest. Results revealed a significant correlational relationship between the measure of intrinsic religious orientation and two of the four measures of distress-hopelessness and death anxiety. A positive significant correlation between extrinsic religious orientation and negative problem orientation was also found. Overall, these results suggest the need to test competing models, in an effort to understand the relationship among these variables, and ultimately how religious orientation can be facilitated in a manner that promotes adjustment among cancer patients.