CRLF2 rearrangement in Ph-like acute lymphoblastic leukemia predicts relative glucocorticoid resistance that is overcome with MEK or Akt inhibition.

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a genetically heterogeneous subtype of B-cell ALL characterized by chromosomal rearrangements and mutations that result in aberrant cytokine receptor and kinase signaling. In particular, chromosomal rearrangements resulting in the overexpression of cytokine receptor-like factor 2 (CRLF2) occur in 50% of Ph-like ALL cases. CRLF2 overexpression is associated with particularly poor clinical outcomes, though the molecular basis for this is currently unknown. Glucocorticoids (GCs) are integral to the treatment of ALL and GC resistance at diagnosis is an important negative prognostic factor. Given the importance of GCs in ALL therapy and the poor outcomes for patients with CRLF2 overexpression, we hypothesized that the aberrant signal transduction associated with CRLF2 overexpression might mediate intrinsic GC insensitivity. To test this hypothesis, we exposed Ph-like ALL cells from patient-derived xenografts to GCs and found that CRLF2 rearranged (CRLF2R) leukemias uniformly demonstrated reduced GC sensitivity in vitro. Furthermore, targeted inhibition of signal transduction with the MEK inhibitor trametinib and the Akt inhibitor MK2206, but not the JAK inhibitor ruxolitinib, was sufficient to augment GC sensitivity. These data suggest that suboptimal GC responses may in part underlie the poor clinical outcomes for patients with CRLF2 overexpression and provide rationale for combination therapy involving GCs and signal transduction inhibitors as a means of enhancing GC efficacy

Changes in insulin and insulin signaling in Alzheimer\u27s disease: Cause or consequence?

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD

Standardised library instruction assessment: an institution-specific approach

Introduction We explore the use of a psychometric model for locally-relevant, information literacy assessment, using an online tool for standardised assessment of student learning during discipline-based library instruction sessions. Method A quantitative approach to data collection and analysis was used, employing standardised multiple-choice survey questions followed by individual, cognitive interviews with undergraduate students. The assessment tool was administered to five general education psychology classes during library instruction sessions. AnalysisDescriptive statistics were generated by the assessment tool. Results. The assessment tool proved a feasible means of measuring student learning. While student scores improved on every survey question, there was uneven improvement from pre-test to post-test for different questions. Conclusion Student scores showed more improvement for some learning outcomes over others, thus, spending time on fewer concepts during instruction sessions would enable more reliable evaluation of student learning. We recommend using digital learning objects that address basic research skills to enhance library instruction programmes. Future studies will explore different applications of the assessment tool, provide more detailed statistical analysis of the data and shed additional light on the significance of overall scores

LOGISTICAL COSTS AND RISKS OF MARKETING GENETICALLY MODIFIED WHEAT

Genetically modified (GM) grains have increased in importance. Moving biotech grains from producers to processors is a challenge for the grain handling system that could involve increased segregations. The objective of this research is to determine how testing strategies affect the logistical costs of a grain pipeline when GM wheat is present. A logistical model was developed and simulated to analyze impacts of uncertainty in demand, receipts, test accuracy, rail deliveries, and transit time. Sensitivities were conducted on certain variables to determine their effects on logistical costs. Analysis revealed that logistical costs are impacted by the number of quality categories and uncertainties in the system. Adding GM grains increased costs due to testing requirements and increased segregation demands as the number of wheat categories rises.Genetically Modified (GM) Grains, Logistical Costs, Testing, Risk, Segregation, Crop Production/Industries, Research and Development/Tech Change/Emerging Technologies,

LOGISTICAL COSTS AND STRATEGIES FOR WHEAT SEGREGATION

Special segregations that provide unique qualities for end use products are being specified by buyers. As users of wheat become more specific about quality, the number of quality segregations that the logistical pipeline must accommodate increases. The additional cost of increased grain segregations will influence the optimal level of wheat variety segregations marketed in a supply chain. The primary objective of this research is to develop a model that captures the logistical costs of increased grain segregations in the marketing system. A simulation model was developed to add logistical uncertainty in demand, receipts, rail deliveries, and transit time. Sensitivities were conducted on certain variables to determine their effects on logistical costs. Logistical costs increase as more segregations are added. In addition, increasing uncertainty into the system raises logistical costs. Pipeline configuration also affects costs as the number of categories/storage bins present at origin may differ from the wheat categories demanded or the number of storage bins present at the export elevator.wheat, segregations, Crop Production/Industries,

Introduction to a Special Issue on the Impact of Immigrant Legalization Initiatives: International Perspectives on Immigration and the World of Work

This article is the third in a series to celebrate the 70th anniversary of the ILR Review. The series features articles that analyze the state of research and future directions for important themes the journal has featured over its many years of publication. In this issue, we also feature a special cluster of articles and book reviews on one of the most critical labor market issues across the globe—the legalization and integration of immigrants into national labor markets. Despite the urgent need for immigration reform in the United States, there is a paucity of US research that looks at the impact of a shift from unauthorized to legal immigrant status in the workplace. The US immigration literature has also paid little attention to immigrant legalization policies outside of the United States, despite the fact that other countries have implemented such policies with far more regularity. The articles in this special issue draw on studies of legalization initiatives in major immigrant destinations: Canada, Italy, and the United Kingdom. Together they underscore the importance of cross-national perspectives for understanding the range of legalization programs and their impact on immigrant workers, the workplace, and the labor market. These findings contribute to key questions in migration scholarship and inform the global policy debate surrounding the integration and well-being of immigrant

Generalized Hurst exponent and multifractal function of original and translated texts mapped into frequency and length time series

A nonlinear dynamics approach can be used in order to quantify complexity in written texts. As a first step, a one-dimensional system is examined : two written texts by one author (Lewis Carroll) are considered, together with one translation, into an artificial language, i.e. Esperanto are mapped into time series. Their corresponding shuffled versions are used for obtaining a "base line". Two different one-dimensional time series are used here: (i) one based on word lengths (LTS), (ii) the other on word frequencies (FTS). It is shown that the generalized Hurst exponent $h(q)$ and the derived $f(\alpha)$ curves of the original and translated texts show marked differences. The original "texts" are far from giving a parabolic $f(\alpha)$ function, - in contrast to the shuffled texts. Moreover, the Esperanto text has more extreme values. This suggests cascade model-like, with multiscale time asymmetric features as finally written texts. A discussion of the difference and complementarity of mapping into a LTS or FTS is presented. The FTS $f(\alpha)$ curves are more opened than the LTS onesComment: preprint for PRE; 2 columns; 10 pages; 6 (multifigures); 3 Tables; 70 reference

THE TEXAS RICE INDUSTRY COALITION FOR THE ENVIRONMENT (R.I.C.E.): MAIN POINTS FROM SIX FOCUS GROUPS

The Texas Rice Industry Coalition for the Environment (R.I.C.E.) was formed in February, 1995. Their stated mission is to build a coalition of interests to foster and strengthen relationships between the rice industry and the natural resources of our rice-producing area in Texas. In June, 1995, a series of six focus groups was conducted. These round table discussions involved two groups of producers (from the East Side and West Side of Houston), two groups of environmentalists in the Houston area, and two groups of non-farming Houstonians (adults and children). These focus groups were structured to elicit opinions from various viewpoints concerning the opportunities, challenges, and priorities of Texas R.I.C.E. The goal of the two producers focus groups conducted on the East Side and the West Side of Houston was to determine whether Texas R.I.C.E.'s activities were widely known and to ascertain producers' viewpoints on the coalition's priorities. Producers were agreed on their key concerns regarding compliance with environmental policy - they face a cost-price squeeze and therefore one-size-fits-all regulations are particularly burdensome. Water quality and quantity were most often mentioned as key factors in the continued viability of the rice industry in Texas. Producers recognize the natural synergy between rice production and waterfowl habitat enhancement, yet they are concerned because waterfowl habitat places increased demands on scarce water. Rice producers are concerned about the public being largely ignorant and uninterested in the environmental benefits of rice production, and they endorsed two-way education between rice producers and environmentalists. No clear consensus emerged in the focus group discussions about the role for Texas R.I.C.E. in lobbying. Some rice producers see education and lobbying as conflicting activities and would prefer for Texas R.I.C.E. to focus on education. Others were positive about collaborative opportunities between rice producers' lobbyists and environmental interest groups' lobbyists. The two environmental focus groups were a mix of bird-watchers, hunters, hikers and conservationists. These environmentalists had a good idea of where rice is grown in Texas and knew that rice production is declining in the state. Their major concerns about the environmental effects from rice production were water usage and water quality, agri-chemical runoff, food and habitat for migratory birds, and trade-offs concerning wetlands. In sum, they appreciated that rice production makes a positive contribution to waterfowl habitat. They were concerned that lost Texas rice acreage will be replaced with urban land uses, thus reducing wildlife habitat benefits. They viewed rice production as being environmentally friendly compared with other types of agricultural production, such as cotton farming. They were favorably impressed that rice producers were taking the initiative to form a coalition. They were anxious to work collaboratively and offered several concrete suggestions about forums and issues for educational campaigns. They suggested that consumptive and non-consumptive users of wildlife habitat (such as hunters and bird-watchers, respectively) should compensate private landowners for allowing access. They acknowledged problems with adversarial attitudes going both ways between environmentalists and rice producers; they brainstormed about how Texas R.I.C.E. could help break down barriers. The general public adult focus group, comprised of non-farming Houstonians, established a general interest and awareness concerning rice production. However, the Houstonians participating in this focus group were uninformed about the waterfowl habitat benefits associated with rice production. They offered positive endorsement of the Texas R.I.C.E. effort and expressed sincere (and specific) interests in educational programming. The general public children focus group included several children from the Clear Lake area south of Houston. These children exhibited a natural inquisitiveness and concern regarding the environment and food safety. They were largely ignorant of commercial agriculture, excepting several recollections of "visits to relatives' farms." They expressed considerable interest in more agricultural-related curriculum being incorporated into their science and/or social studies curricula.Environmental Economics and Policy,

Information Content of Spontaneous Symmetry Breaking

We propose a measure of order in the context of nonequilibrium field theory and argue that this measure, which we call relative configurational entropy (RCE), may be used to quantify the emergence of coherent low-entropy configurations, such as time-dependent or time-independent topological and nontopological spatially-extended structures. As an illustration, we investigate the nonequilibrium dynamics of spontaneous symmetry-breaking in three spatial dimensions. In particular, we focus on a model where a real scalar field, prepared initially in a symmetric thermal state, is quenched to a broken-symmetric state. For a certain range of initial temperatures, spatially-localized, long-lived structures known as oscillons emerge in synchrony and remain until the field reaches equilibrium again. We show that the RCE correlates with the number-density of oscillons, thus offering a quantitative measure of the emergence of nonperturbative spatiotemporal patterns that can be generalized to a variety of physical systems.Comment: LaTeX, 9 pages, 5 figures, 1 tabl

Doubly Perfect Nonlinear Boolean Permutations

Due to implementation constraints the XOR operation is widely used in order to combine plaintext and key bit-strings in secret-key block ciphers. This choice directly induces the classical version of the differential attack by the use of XOR-kind differences. While very natural, there are many alternatives to the XOR. Each of them inducing a new form for its corresponding differential attack (using the appropriate notion of difference) and therefore block-ciphers need to use S-boxes that are resistant against these nonstandard differential cryptanalysis. In this contribution we study the functions that offer the best resistance against a differential attack based on a finite field multiplication. We also show that in some particular cases, there are robust permutations which offers the best resistant against both multiplication and exponentiation base differential attacks. We call them doubly perfect nonlinear permutations