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"Thomas, Frances"
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A critically compassionate approach to financial literacy
A Critically Compassionate Approach to Financial Literacy offers a unique approach to conceptualizing financial literacy. Differentiating between notions of financial worth and personal self-worth, the authors present a description of financial literacy tenets founded in principles of self-awareness and cooperative community that are rooted in principles of compassion. Basing their work on principles of psychological and archeological research that associates personal wellness with self-security based on principles of trust, the authors posit that personal fulfillment occurs independently of accumulated financial resources. Featuring standards for Grades 4 and 8, offering stimulating questions for discussion, and ideas for classroom activities, A Critically Compassionate Approach to Financial Literacy represents an engaging classroom resource for elementary and middle level social studies methods courses as well as those that concern topics that relate to culturally responsive teaching and social justice. Regardless of your financial background and awareness, this text will challenge your thinking about the meaning of being financially literate and the consequences for society. -- Provided by publisher.
Book
Effective drug combinations in breast, colon and pancreatic cancer cells
Combinations of anti-cancer drugs can overcome resistance and provide new treatments
1
,
2
. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable or
KRAS
-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or
KRAS
–
TP53
double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.
A survey of potency and efficacy of 2,025 clinically relevant two-drug combinations against 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines identifies rare synergistic effects of anticancer drugs, informing rational combination treatments for specific cancer subtypes.
Journal Article
Fundamental financial accounting concepts
\"Technology has changed accounting practice. Gone are the days where accountants used pens, paper, and calculators to maintain records and prepare statements. Indeed, most companies use computer software that simplifies data entry, recordkeeping, and statement preparation. Today's accountants spend less time preparing financial information and more time consulting and advising clients. To remain relevant, accounting education must move beyond the traditional preparer approach. The first step in learning how to advise clients is to understand how business professionals incorporate accounting in the decision-making process. Business professionals tend to think about bottom-line consequences. If I do this or that, how will it affect my company's net income, total assets, cash flow, and so on. To promote bottomline thinking, we take the student one step beyond the recording process. Specifically, we employ a financial statements model to show them how the journal entries affect financial statements. The model arranges the balance sheet, income statement, and statement of cash flows horizontally across a single line of text\"-- Provided by publisher.
Book
Drug mechanism‐of‐action discovery through the integration of pharmacological and CRISPR screens
Low success rates during drug development are due, in part, to the difficulty of defining drug mechanism‐of‐action and molecular markers of therapeutic activity. Here, we integrated 199,219 drug sensitivity measurements for 397 unique anti‐cancer drugs with genome‐wide CRISPR loss‐of‐function screens in 484 cell lines to systematically investigate cellular drug mechanism‐of‐action. We observed an enrichment for positive associations between the profile of drug sensitivity and knockout of a drug's nominal target, and by leveraging protein–protein networks, we identified pathways underpinning drug sensitivity. This revealed an unappreciated positive association between mitochondrial E3 ubiquitin–protein ligase
MARCH5
dependency and sensitivity to MCL1 inhibitors in breast cancer cell lines. We also estimated drug on‐target and off‐target activity, informing on specificity, potency and toxicity. Linking drug and gene dependency together with genomic data sets uncovered contexts in which molecular networks when perturbed mediate cancer cell loss‐of‐fitness and thereby provide independent and orthogonal evidence of biomarkers for drug development. This study illustrates how integrating cell line drug sensitivity with CRISPR loss‐of‐function screens can elucidate mechanism‐of‐action to advance drug development.
Synopsis
This study integrates pharmacological and CRISPR screens in 484 cancer cell lines to systematically investigate anticancer drug mechanism of action, yielding insights into the genetic contexts and cellular networks underpinning drug response.
CRISPR screens reveal important aspects of drug mechanism‐of‐action, specifically in the context of cellular activity, isoform specificity, off‐target and polypharmacological effects.
By leveraging protein interaction networks that underlie drug‐responses, novel drug‐target interactions involving anti‐apoptotic MCL1 inhibitors are identified.
Improved pharmacogenomic biomarker discovery using two independent and orthogonal cell viability screens.
Graphical Abstract
This study integrates pharmacological and CRISPR screens in 484 cancer cell lines to systematically investigate anticancer drug mechanism of action, yielding insights into the genetic contexts and cellular networks underpinning drug response.
Journal Article
Structural basis for the rescue of hyperexcitable cells by the amyotrophic lateral sclerosis drug Riluzole
Neuronal hyperexcitability is a key element of many neurodegenerative disorders including the motor neuron disease Amyotrophic Lateral Sclerosis (ALS), where it occurs associated with elevated late sodium current (I
NaL
). I
NaL
results from incomplete inactivation of voltage-gated sodium channels (VGSCs) after their opening and shapes physiological membrane excitability. However, dysfunctional increases can cause hyperexcitability-associated diseases. Here we reveal the atypical binding mechanism which explains how the neuroprotective ALS-treatment drug riluzole stabilises VGSCs in their inactivated state to cause the suppression of I
NaL
that leads to reversed cellular overexcitability. Riluzole accumulates in the membrane and enters VGSCs through openings to their membrane-accessible fenestrations. Riluzole binds within these fenestrations to stabilise the inactivated channel state, allowing for the selective allosteric inhibition of I
NaL
without the physical block of Na
+
conduction associated with traditional channel pore binding VGSC drugs. We further demonstrate that riluzole can reproduce these effects on a disease variant of the non-neuronal VGSC isoform Nav1.4, where pathologically increased I
NaL
is caused directly by mutation. Overall, we identify a model for VGSC inhibition that produces effects consistent with the inhibitory action of riluzole observed in models of ALS. Our findings will aid future drug design and supports research directed towards riluzole repurposing.
The authors here present a high-resolution structure of riluzole bound to a voltage-gated sodium channel. This identifies an intramembranous drug-binding site allowing the potent riluzole-induced enhancement of channel inactivation, normalising the hyperexcitable cellular states found in ALS models. This supports riluzole repurposing and aids future drug design efforts.
Journal Article
Martyred Anglicans: The Persecution of the Nippon Sei Kō Kai and its Implications for Anglican Ecclesiology
The Great Depression, which swept over Japan in 1930, had a profound impact on the general public's quality of life, exacerbating the social unrest that had threatened to emerge as Japan rapidly industrialized in the second half of the nineteenth century. [...]the Peace Preservation Law (Chian Iji Ho, 1925), originally enacted to suppress communism, was increasingly applied broadly to eradicate all organized resistance to the developing conflict.\" [...]Japan became gripped by totalitarian nationalism and military fascism, which, while not as wholly transformative as in contemporaneous German society, nevertheless shaped everyday life in the nation until the disaster had run its full course. [...]religious control has historically been a political concern of Japanese governments, a key example being the ban on and near-total eradication of Christianity in the seventeenth century. Potential sources of opposition to state authority were identified for particular attention, and among the categories of \"potentially disruptive 'social movements\" singled out by the Home Ministry for observation were \"religious groups (particularly Christians).
Journal Article
Improving Service to Low-Income Families by a Faith-Based Ministerial Alliance
Families in the United States often experience financial hardships that force them to seek government or social service assistance in order to survive or meet their day-to-day needs. Faith-based organizations (FBOs) date as far back as 1912 and were established to serve as social service agencies addressing the needs of low-income people (Bielefeld & Cleveland, 2013). Through the Charitable Choice Act of 1996, these organizations were eligible to receive funding from the government to assist low-income families (Diiulio, 2004). The Interdenominational Ministerial Alliance of Dover and Vicinity (IMA) is one of the several faith-based organizations in Dover, Delaware, that assists families who experience financial hardship. The purpose of this study was to investigate whether the IMA has impacted the financial stability of its clients. Two research questions guided this qualitative ethnographic study which consisted of recorded interviews about the financial behavior of clients. A total of 20 randomly selected IMA clients were interviewed about their economic situations and the perception of the services provided by the IMA. The three emergent themes from this study were: 1) meeting emergent needs, 2) expectant lifestyles, and 3) transportation. The findings revealed that there is a need to develop and offer financial literacy programs and courses to assist IMA clients to become economically stable and more self-reliant. Additionally, through organizational change, the IMA will be able to better ensure its sustainability in meeting its clients’ needs during times of financial crisis.
Dissertation
Genetic architecture underlying convergent evolution of egg-laying behavior in a seed-feeding beetle
Independent populations subjected to similar environments often exhibit convergent evolution. An unresolved question is the frequency with which such convergence reflects parallel genetic mechanisms. We examined the convergent evolution of egg-laying behavior in the seed-feeding beetle
Callosobruchus maculatus
. Females avoid ovipositing on seeds bearing conspecific eggs, but the degree of host discrimination varies among geographic populations. In a previous experiment, replicate lines switched from a small host to a large one evolved reduced discrimination after 40 generations. We used line crosses to determine the genetic architecture underlying this rapid response. The most parsimonious genetic models included dominance and/or epistasis for all crosses. The genetic architecture underlying reduced discrimination in two lines was not significantly different from the architecture underlying differences between geographic populations, but the architecture underlying the divergence of a third line differed from all others. We conclude that convergence of this complex trait may in some cases involve parallel genetic mechanisms.
Journal Article
Rapid Evolution of Lifespan in a Novel Environment: Sex-Specific Responses and Underlying Genetic Architecture
Animal lifespans can vary substantially among closely related species and even among conspecific populations, but it is often difficult to identify environmental and genetic factors producing such variation. We used experimental evolution to examine how transfer to a novel environment affects adult lifespan and rates of senescence in a seed-feeding beetle. Three replicate lines of
Callosobruchus maculatus
(F.) were switched to a new host plant (cowpea), and each evolved shorter adult lifespans compared to a line maintained on the ancestral host (mung bean). However, the evolution of lifespan differed between the sexes; female lifespan was reduced by ~11% in all cowpea replicates, whereas male lifespan decreased by an average of only 5.6% and the magnitude of the reduction varied among replicates. Reduced lifespan in lines switched to cowpea mirrored the shorter lifespan observed in a separate population chronically associated with cowpea. We then performed crosses between the mung bean and cowpea lines to estimate the genetic architecture underlying the rapid evolution of a shorter lifespan on cowpea. Dominance (overdominance) contributed substantially to the difference between the cowpea and mung bean lines for female lifespan but not for male lifespan. However, details of the genetic architecture varied among the three replicate crosses, so that the convergent evolution of shorter female lifespan in the different cowpea lines did not arise from identical allelic substitutions. Our study demonstrates that insect lifespan can be predictably modified by a switch to a novel host plant, that both the magnitude of this response and its underlying genetic architecture can be sex-specific, and that convergent evolution of a complex trait such as lifespan can arise from different genetic mechanisms.
Journal Article
Teacher Team Performance and Its Effect on the Academic Achievement of Students in Upper Elementary Classroom
Today, students in all states are expected to meet state standards and to be on grade level by the school year 2013-2014 to fulfill the requirements of the No Child Left Behind Act. Student failures in reading and math on the CRCT created a major concern for the administration and teachers at a rural elementary school in Georgia. Following grade level meetings between teachers and administration, a decision was made to form teacher teams for the 2006-2007 school year in third, fourth, and fifth grades as a strategy to improve student achievement. This study surveyed those teachers’ views on the performance of the teacher teams and its effect on student achievement in the upper elementary grades. Ninety-three percent of the participants revealed that they felt their team was successful. The study concluded that teachers felt that the process of teaming was working well at the school, but the teachers felt their teams had not resulted in the level of increased student achievement as measured on the CRCT that they had desired.
Dissertation