A LONGITUDINAL STUDY OF STUDENT’S REPRESENTATIONS FOR DIVISION OF FRACTIONS

The representations that students use as part of their mathematical problem solving can provide us with a window into their grasp of the concepts they are exploring and developing. In this paper, the author indicates how these representations can evolve over time and enrich the understanding of division of fractions, often thought to be the most difficult of elementary school mathematical topics. The results of this research suggest that when appropriate problems are provided for students, in a meaningful context, they can demonstrate understanding of division of fractions that is durable over time, and that they are able to flexibly move back and forth between and among representations, choosing what they deem to be appropriate forms for a particular situation

New Insights into Molecular Mechanisms of Fludarabine

Nucleotide analogs (e.g. fludarabine) are antimetabolites used in the treatment of a wide variety of hematological malignancies and solid tumors. Upon being metabolized to their active triphosphate form, these agents are incorporated into DNA. Among other molecular targets, their incorporation may lead to activation of base excision repair (BER) pathway. The molecular mechanism of BER recognition and repair of the incorporated fludarabine has not yet been elucidated. The main focus of this research was to study the involvement of BER pathway in the response to fludarabine induced DNA damage. Also, the possibility of enhancing antineoplastic activity of fludarabine by inhibition of BER (e.g. methoxyamine) was investigated. Firstly, capacity of uracil DNA glycosylase to recognize and excise incorporated fludarabine was established. Secondly, the formation of abasic (AP) sites after fludarabine treatment was confirmed in different human cancer cell lines. These results demonstrated that incorporated fludarabine, acting as an abnormal base in DNA, initiates BER. The possibility to enhance fludarabine-induced damage by inhibiting BER was then considered. Exposure of cells to fludarabine and methoxyamine (MX) combined regimens caused increased apoptosis, clonogenic death, upregulation of some key BER proteins, enhanced DNA strand breaks. It also enhanced anti-tumor effects in human xenografts. This response of cells to fludarabine plus MX was due to MX binding to the ara-AP sites formed by fludarabine, thus turning the repairable DNA damage into lethal lesions. In addition, mitochondrial DNA was found to be targeted by fludarabine and fludarabine plus MX. Apoptotic signaling from nuclear and mitochondrial DNA damage triggered mitochondrial mediated cell death during BER disruption by MX. The modulation of fludarabine cytotoxicity by manipulating BER via MX was analyzed in a similar series of experiments using primary lymphocytes obtained from CLL patients. MX enhancement of activity of fludarabine was confirmed the

The association between sexual orientation and labor market outcomes

The purpose of this research is to begin to describe various aspects of interactions with the labor market (e.g. employment status, individual income, household income) based on sexual orientation, using nationally representative data from the General Social Survey. Much of the previous research suggests that any observed differences can be attributed to employee choice of occupation or other voluntary aspects of employment. Furthermore, previous research has found wage premiums for gay women and penalties for gay men, with sexual orientation, not gender, as the lead cause. Based on this current data, I assert that any observed difference is an artifact of both sexual orientation and gender, impacting equal and unbiased access to the labor market. I conclude that gay men and women are more educated than their straight counterparts yet have lower predicted household incomes and individual incomes. This effect is constant for gay men more than gay women

Surveying Identities in Context: Race, Gender & Sexual Orientation ‘at Work’

Researchers, practitioners and common practice have imputed a great deal of power onto categories of social identity (e.g. race, sexual orientation, gender, religion). It common practice to collect demographic and identifying information on the categories to which we belong in settings ranging from the Census to the online shopping profile. Moreover, we have come to expect that this information will be used to make meaningful decisions on government program funding, targeted marketing, college recruitment and so much more. We also know that minority identities have a long history of negatively impacting individuals in employment, housing and other realms of daily life beyond ‘top-down’ decisions, such as government funding. While research has examined best practices for conceptualizing these categories, it has largely done so using terms that may not capture the nuance and actual identity experiences of respondents (e.g. offering a ‘gay’ category but not a ‘queer’ category). Additionally, little research has focused on how these categories are understood by individuals with non-normative or multiple minority identities (i.e. intersectional identities such as being both LGBT and black) and what, if any, such identities have on lived experiences. The literature generally presumes that one’s identity is stagnant - meaning, you self-identify and are known (as a sexual minority, by your racial identities, etc.) the same across all situations. This (potentially incorrect) approach likely impacts sexual minorities disproportionately, who still lack sufficient representation in the literature, and multiple minorities, whose identities are not usually considered in context. The timeliness of addressing this gap in the research is evidenced by national conversations around the Orlando Pulse nightclub attacks, the Supreme Court cases surrounding religious exemption, the Black Lives Matter movement and many others. In response, this work proposes a three-part investigation: first, a meta-analysis of existing literature on identity and patterns of self-identification using national samples; second, cognitive interviews to investigate how respondents with multiple minority identities understand and answer questions around their identities, with an emphasis on disclosure (to whom they ‘come out’ and how) ; and third, a pilot survey using questions responding to the findings of the cognitive interviews on disclosure, with an emphasis on practices and experiences in the workplace in order to provide a specific context for examination of outcomes

Removal of Uracil by Uracil DNA Glycosylase Limits Pemetrexed Cytotoxicity: Overriding the Limit with Methoxyamine to Inhibit Base Excision Repair

Uracil DNA glycosylase (UDG) specifically removes uracil bases from DNA, and its repair activity determines the sensitivity of the cell to anticancer agents that are capable of introducing uracil into DNA. In the present study, the participation of UDG in the response to pemetrexed-induced incorporation of uracil into DNA was studied using isogenic human tumor cell lines with or without UDG (UDG+/+/UDG−/−). UDG−/− cells were very sensitive to pemetrexed. Cell killing by pemetrexed was associated with genomic uracil accumulation, stalled DNA replication, and catastrophic DNA strand breaks. By contrast, UDG+/+ cells were \u3e10 times more resistant to pemetrexed due to the rapid removal of uracil from DNA by UDG and subsequent repair of the resultant AP sites (abasic sites) via the base excision repair (BER). The resistance to pemetrexed in UDG+/+ cells could be reversed by the addition of methoxyamine (MX), which binds to AP sites and interrupts BER pathway. Furthermore, MX-bound AP sites induced cell death was related to their cytotoxic effect of dual inactivation of UDG and topoisomerase IIα, two genes that are highly expressed in lung cancer cells in comparison with normal cells. Thus, targeting BER-based therapy exhibits more selective cytotoxicity on cancer cells through a synthetic lethal mechanism

New insights into the synergism of nucleoside analogs with radiotherapy

Nucleoside analogs have been frequently used in combination with radiotherapy in the clinical setting, as it has long been understood that inhibition of DNA repair pathways is an important means by which many nucleoside analogs synergize. Recent advances in our understanding of the structure and function of deoxycytidine kinase (dCK), a critical enzyme required for the anti-tumor activity for many nucleoside analogs, have clarified the mechanistic role this kinase plays in chemo- and radio-sensitization. A heretofore unrecognized role of dCK in the DNA damage response and cell cycle machinery has helped explain the synergistic effect of these agents with radiotherapy. Since most currently employed nucleoside analogs are primarily activated by dCK, these findings lend fresh impetus to efforts focused on profiling and modulating dCK expression and activity in tumors. In this review we will briefly review the pharmacology and biochemistry of the major nucleoside analogs in clinical use that are activated by dCK. This will be followed by discussions of recent advances in our understanding of dCK activation via post-translational modifications in response to radiation and current strategies aimed at enhancing this activity in cancer cells

ОЦЕНКА РЕЗУЛЬТАТОВ ПОКАЗАТЕЛЕЙ ЛАБОРАТОРНОГО ОБСЛЕДОВАНИЯ ЖЕНЩИН РЕПРОДУКТИВНОГО ВОЗРАСТА, БОЛЬНЫХ АДЕНОМИОЗОМ ПОСЛЕ ПЕРЕНЕСЕННОГО COVID-19

Заданние исследования состояло в проведении клинического анализа результатов лабораторного обследования женщин репродуктивного возраста, больных аденомиозом после перенесеного COVID–19. Материалы и методы исследования. Под нашим наблюдением находилось 30 практически здоровых женщин (группа А), 60 женщин, больных аденомиозом I – II степени тяжести (группа В), 60 – больных аденомиозом I – IV степени тяжести (группа С), которые перенесли COVID-19. Проведено лабораторное обследование женщин, которое включало определение показателей клинического, биохимического исследования биологических жидкостей (кровь, моча, влагалищное содержание), в том числе и методом полимеразно-цепной реакции. Результаты. Анализ результатов исследований биологического материала показал достоверные отличия показателей, изучаемых между группами обследуемых. У пациенток больных аденомиозом, перенесшим COVID-19 выявлено в крови наличие процессов гиперкоагуляции крови, повышение показателей биологических маркеров воспаления: С-реактивный белок, D-димера, прокальцитонина, лактатдегидрогеназа и снижение уровня  ферритина, снижение уровня витамина D (общего), магния, общего белка, повышение уровня липопротеидов высокой плотности, креатинина, аспартатаминотрансфераза, аланинаминотрансфераза, щелочной фосфатазы. Достоверно увеличивался  уровень эстрадиола и снижалось содержание прогестерона, лютеинизирующего и фолликулостимулирующего гормонов. По данным результатов микроскопической характеристики биоценоза влагалищного содержимово, увеличилось число наблюдений промежуточного типа, дисбиоза, вагинита, выявлен достоверный рост частоты Virus herpes simplex, Cytomegalovirus. Гистоморфологические исследования тканей удалённых органов (матка, придатки матки) во время хирургического лечения подтвердили наличие тромбов. Выводы. У женщин репродуктивного возраста, больных аденомиозом после перенесенного заболевания СОVID-19, анализ результатов лабораторных исследованиий  подтвердил наличие гиперкоагуляции, тромбообразования, активации биологических маркеров воспаления, анемии, воспалительных процессов внутренних половых органов. Клиническая оценка результатов показателей лабораторного обследования женщин, больных аденомиозом после перенесенного COVID-19 имеет практическое значение, которое заключается в превентивной профилактике возникновения возможных осложнений