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Identifying how small molecules act to kill malaria parasites can lead to new chemically validated targets. By pressuring Plasmodium falciparum asexual blood stage parasites with three novel structurally-unrelated antimalarial compounds (MMV665924, MMV019719 and MMV897615), and performing whole-genome sequence analysis on resistant parasite lines, we identify multiple mutations in the P. falciparum acyl-CoA synthetase (ACS) genes PfACS10 (PF3D7_0525100, M300I, A268D/V, F427L) and PfACS11 (PF3D7_1238800, F387V, D648Y, and E668K). Allelic replacement and thermal proteome profiling validates PfACS10 as a target of these compounds. We demonstrate that this protein is essential for parasite growth by conditional knockdown and observe increased compound susceptibility upon reduced expression. Inhibition of PfACS10 leads to a reduction in triacylglycerols and a buildup of its lipid precursors, providing key insights into its function. Analysis of the PfACS11 gene and its mutations point to a role in mediating resistance via decreased protein stability.

Adaptive learning (AL) courseware holds promise for helping break down challenges students face in college. In 2016-2017 we developed an AL Political Science course, Global Issues, implemented it across 51 classes and more than 5,200 students over the next two academic years, and initiated a study to assess student perceptions and performance. In each semester, except spring 2018 when half the sections used non-AL courseware, all sections were taught using the AL courseware. Across these AL sections and on every question in a survey of student perceptions, students gave highly positive perceptive ratings of the courseware. In the spring 2018 assessment of the AL courseware versus non-AL courseware, the perceptive differences between the adaptive and non-adaptive sections were statistically significant on 12 of 14 questions (though the difference in online classes was not significant and we found significant differentiation based on instructor rank). As for student performance, the difference between AL and non-AL classes again showed overall significance, though with marked between-instructor differences and again not in online classes. It is also important to note that first-year status informed the performance results, and the average DFW rate fell significantly once the AL courseware was introduced. Our findings support the case that AL courseware can be one tool that helps provide a useful foundation for student progression, satisfaction, and performance.

Winning teams have it, losing teams want it, and every coach wants to create it at the start of a new season. Culture can influence and determine the success or failures of any athletic program, especially if it is ignored. Any team needs a recipe for success, and one can create greatness by training and developing your team to be their best. However, thousands of intangibles exist in the equation, and determining the importance of life skills can play a large part in a team's positive or negative experience. Every coach has the power to change the culture of his or her program, all they need is a positive attitude and ability to be self-reflective. Yet, it's ultimately up to the athletes to step and accept the challenge of any opportunity when provided the tools for success.

Undergraduate business law courses typically utilize traditional textbooks organized by topic. Individual chapters, address the usual topics including contracts, torts, the court system and ethics. An innovative approach to facilitating a business law course involves segregating sections of the course into common business disciplines. Rather than the abstract teaching of legal concepts, substantive material is presented in well defined sections including management, finance, accounting, real estate, marketing, and human resource management. Each section is defined by excerpts of published cases in private law, public law, preventative law and ethics. Individual disciplines are highlighted by instructive and provocative discussion questions following actual court opinions. Team teaching is an essential ingredient in discipline based instruction. Faculty members from specific disciplines are invited to participate and contribute to the course. The curriculum is presented in an applied format and relevant to the study and practice of business administration. Students are asked to apply legal concepts and issues to the individual disciplines they are studying in a business school format.

BackgroundThe objective of this study was to validate a simple predictive model for survival of patients with advanced cancer.MethodsPrevious studies with training and validation datasets developed a model predicting survival of patients referred for palliative radiotherapy using three readily available factors: primary cancer site, site of metastases and Karnofsky performance score (KPS). This predictive model was used in the current study, where each factor was assigned a value proportional to its prognostic weight and the sum of the weighted scores for each patient was survival prediction score (SPS). Patients were also classified according to their number of risk factors (NRF). Three risk groups were established. The Radiation Therapy and Oncology Group (RTOG) 9714 data was used to provide an additional external validation set comprised of patients treated among multiple institutions with appropriate statistical tests.ResultsThe RTOG external validation set comprised of 908 patients treated at 66 different radiation facilities from 1998 to 2002. The SPS method classified all patients into the low-risk group. Based on the NRF, two distinct risk groups with significantly different survival estimates were identified. The ability to predict survival was similar to that of the training and previous validation datasets for both the SPS and NRF methods.ConclusionsThe three variable NRF model is preferred because of its relative simplicity.

In addition to the well-documented seasonal cycles of mating and birth, there are also significant seasonal cycles of illness and death among many animal populations. Challenging winter conditions (i.e., low ambient temperature and decreased food availability) can directly induce death via hypothermia, starvation, or shock. Coping with these challenges can also indirectly increase morbidity and mortality by increasing glucocorticoid secretion, which can compromise immune function. Many environmental challenges are recurrent and thus predictable; animals could enhance survival, and presumably increase fitness, if they could anticipate immunologically challenging conditions in order to cope with these seasonal threats to health. The annual cycle of changing photoperiod provides an accurate indicator of time of year and thus allows immunological adjustments prior to the deterioration of conditions. Pineal melatonin codes day length information. Short day lengths enhance several aspects of immune function in laboratory studies, and melatonin appears to mediate many of the enhanced immunological effects of photoperiod. Generally, field studies report compromised immune function during the short days of autumn and winter. The conflict between laboratory and field data is addressed with a multifactor approach. The evidence for seasonal fluctuations in lymphatic tissue size and structure, as well as immune function and disease processes, is reviewed. The role of pineal melatonin and the hormones regulated by melatonin is discussed from an evolutionary and adaptive functional perspective. Finally, the clinically significance of seasonal fluctuations in immune function is presented. Taken together, it appears that seasonal fluctuations in immune parameters, mediated by melatonin, could have profound effects on the etiology and progression of diseases in humans and nonhuman animals. An adaptive functional perspective is critical to gain insights into the interaction among melatonin, immune function, and disease processes.

In addition to the well-documented seasonal cycles of mating and birth, there are also significant seasonal cycles of illness and death among many animal populations. Challenging winter conditions (i.e., low ambient temperature and decreased food availability) can directly induce death via hypothermia, starvation, or shock. Coping with these challenges can also indirectly increase morbidity and mortality by increasing glucocorticoid secretion, which can compromise immune function. Many environmental challenges are recurrent and thus predictable; animals could enhance survival, and presumably increase fitness, if they could anticipate immunologically challenging conditions in order to cope with these seasonal threats to health. The annual cycle of changing photoperiod provides an accurate indicator of time of year and thus allows immunological adjustments prior to the deterioration of conditions. Pineal melatonin codes day length information. Short day lengths enhance several aspects of immune function in laboratory studies, and melatonin appears to mediate many of the enhanced immunological effects of photoperiod. Generally, field studies report compromised immune function during the short days of autumn and winter. The conflict between laboratory and field data is addressed with a multifactor approach. The evidence for seasonal fluctuations in lymphatic tissue size and structure, as well as immune function and disease processes, is reviewed. The role of pineal melatonin and the hormones regulated by melatonin is discussed from an evolutionary and adaptive functional perspective. Finally, the clinically significance of seasonal fluctuations in immune function is presented. Taken together, it appears that seasonal fluctuations in immune parameters, mediated by melatonin, could have profound effects on the etiology and progression of diseases in humans and nonhuman animals. An adaptive functional perspective is critical to gain insights into the interaction among melatonin, immune function, and disease processes.

Problem: From April to September 2021, Fiji experienced a second wave of coronavirus disease (COVID-19) precipitated by the Delta variant of concern, prompting a need to strengthen existing data management of positive COVID-19 cases. Context: With COVID-19 cases peaking at 1405 a day and many hospital admissions, the need to develop a better way to visualize data became clear. Action: The Fiji Ministry of Health and Medical Services, the World Health Organization and the United Nations Office for the Coordination of Humanitarian Affairs collaborated to develop an online clinical dashboard to support better visualization of case management data. Outcome: The dashboard was used across Fiji at national, divisional and local levels for COVID-19 management. At the national level, it provided real-time reports describing the surge pattern, severity and management of COVID-19 cases across the country during daily incident management team meetings. At the divisional level, it gave the divisional directors access to timely information about hospital and community isolation of cases. At the hospital level, the dashboard allowed managers to monitor trends in isolated cases and use of oxygen resources. Discussion: The dashboard replaced previous paper-based reporting of statistics with delivery of trends and real-time data. The team that developed the tool were situated in different locations and did not meet physically, demonstrating the ease of implementing this online tool in a resource-constrained setting. The dashboard is easy to use and could be used in other Pacific island countries and areas. [ABSTRACT FROM AUTHOR]

Complex error propagation is reduced to formula and data entry into a Mathcad worksheet or an Excel spreadsheet. The Mathcad routine uses both symbolic calculus analysis and Monte Carlo methods to propagate errors in a formula of up to four variables. Graphical output is used to clarify the contributions to the final error of each of the individual variables as well as illustrate how well the results conform to the normal distribution. The Excel routine allows direct entry of the formula and evaluates the error by numerical approximation of the necessary partial derivatives. Students find the routines much more user friendly and informative than traditional error propagation techniques. (Contains 4 figures.)

Discusses library buildings and their role in building community. Reviews current design trends, including reading and study spaces; collaborative workspaces; technology-free zones; archives and special collections; cultural events spaces; age-specific spaces; shared spaces; natural light and landscapes; and interior design trends. (LRW)

Alternative procedures were investigated for determining the copyright status of brittle monographs to be scanned as part of the national preservation plan for agricultural sciences literature. Copyright searches conducted at Cornell University's printed Catalog of Copyright Entries (averaging seven minutes per title) were 97% in agreement with results of 13-minutes-per-title searches in the U.S. Copyright Office. (Author/AEF)

Four adventure and experiential educators discuss ethical dilemmas encountered in their work: participants coerced by their employer to attend diversity workshops, facilitator responsibilities, conflict between practitioner and client values, school requirements for student evaluation in an adventure physical education class, and correcting a colleague's unsafe practices. (SV)