Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset

Molecular signature of retinoic acid treatment in acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by a block of differentiation at the promyelocytic stage. APL patients respond to pharmacological concentrations of all-trans retinoic acid ( RA) and disease remission correlates with terminal differentiation of leukemic blasts. The PML/RAR oncogenic transcription factor is responsible for both the pathogenesis of APL and for its sensitivity to RA. In order to identify physiological targets of RA therapy, we analysed gene expression profiles of RA-treated APL blasts and found 1056 common target genes. Comparing these results to those obtained in RA-treated U937 cell lines revealed that transcriptional response to RA is largely dependent on the expression of PML/RAR. Several genes involved in the control of differentiation and stem cell renewal are early targets of RA regulation, and may be important effectors of RA response. Modulation of chromatin modifying genes was also observed, suggesting that specific structural changes in local chromatin domains may be required to promote RA-mediated differentiation. Computational analysis of upstream genomic regions in RA target genes revealed nonrandom distribution of transcription factor binding sites, indicating that specific transcriptional regulatory complexes may be involved in determining RA response

Understanding national renewable energy consumption through the lens of hofstede´s cultural dimensions. insights and recommendations for policy makers

This thesis focuses on investigating the ever-evolving relationship between renewable energy consumption and cultural dimensions, aiming to reevaluate the findings from a previous study, and delve deeper by qualitatively analyzing the reasons behind these relationships. The results highlight the relationship between higher levels of renewable energy consumption and lower scores in the cultural dimension of Motivationt towards achievement and success, Uncertainty avoidance, and Power distance. Traits associated with low and high scores in these dimensions are then analyzed, describing how they facilitate or challenge renewable energy consumption using relevant examples, leading to nuanced recommendations for supranational policymakers

Comparing Multiple Stimulus Preference Assessments to the In-the-Moment Reinforcer Analysis

The provision of reinforcement to increase desired behaviors is a crucial element of behavior analytic intervention for individuals diagnosed with Autism Spectrum Disorder. Formal preference assessments, like the multiple stimulus without replacement procedure (MSWO), are often used to determine reinforcers used during intervention. While these types of assessments have been widely investigated, there is no empirical evidence to support that these rigorous methods of reinforcement identification produce higher rates of responding compared to the in-the-moment reinforcer analysis. The present study compared the average number of chips sorted per session on a sorting task when participants were reinforced with items selected based on an MSWO preference assessment versus items provided using in-the-moment reinforcer analysis. The results showed no significant difference in the average number of chips sorted, however there were differences in terms of efficiency

THE ROLE OF THE MURINE HOMEOBOX GENE CUX-1 IN KIDNEY DEVELOPMENT AND POLYCYSTIC KIDNEY DISEASE

The murine homeobox gene cux-1 is evolutionarily conserved in drosophila, mice and humans. Cux-1 contains four DNA binding domains (3 cut repeat domains and a homeodomain) and functions as a transcription factor that represses the expression of the cyclin kinase inhibitor p27 during S-phase of the cell-cycle. Cux-1 is highly expressed in proliferating cells within the nephrogenic zone of developing kidneys. The role of Cux-1 during kidney development and Polycystic Kidney Disease (PKD) is unclear. Cux-1 is a transcription factor that binds to DNA when it is dephosphorylated. Calcineurin A (CnA) is a phosphatase that might be involved in regulating Cux-1 as both are expressed during early kidney development. Previous studies demonstrated that CnA knockout (-/-) mice display renal hypoplasia associated with ectopic expression of p27 in the nephrogenic zone. The opposite phenotype was observed when Cux-1 is overexpressed. Therefore metanephric kidney cultures, overexpressing Cux-1 were grown in the presence of cyclosporine A to inhibit Calcineurin. Overexpression of Cux-1 rescued growth inhibition due to Calcineurin inhibition. Calcineurin inhibition resulted in increased phospho-Cux-1 levels suggesting that Calcineurin may regulate Cux-1 and thus revealing a new pathway in kidney development. The cpk mouse model is the most widely characterized model for PKD. A hallmark of PKD is increased cell proliferation. The mechanism of cell proliferation in PKD is unclear although deregulation of cyclin kinase inhibitors appears to be involved. Cux-1 is highly expressed in cpk kidneys, however it is unclear if Cux-1 is required for PKD. The results here demonstrate that a mutation of Cux-1 (cux-1∆CR1) which lacks a Cathepsin-L proteolytic cleavage site, results in severe PKD when crossed onto cpk mice. Upregulation of Cux-1∆CR1 was observed and correlated with attenuated levels of p27 within cpk kidneys which suggests a potential mechanism for the acceleration of PKD. Alteration of the PKD phenotype by Cux-1 suggests that Cux-1 may act as a candidate modifier gene of PKD. The collection of studies presented within this body of work has helped to elucidate the importance of Cux-1 regulation by post-translational modification which requires further investigation as a critical factor in kidney development and PKD

Learning How to Teach How to Learn English as a Second Language: Reflections from Experience, Praxis, and Theory

This thesis explores the development of professional expertise in teaching ESL. Such expertise incorporates the methodological instructional knowledge, intercultural awareness, and multilingual competence essential to meeting highly diversified learning needs in US classrooms, facilitating globalization of domestic business interests, and enabling the integration of immigrants into American society. I encourage a view of ESL teachers as craftspersons and intellectuals who integrate a reflective approach toward personal experience and a comprehensive awareness of relevant intellectual constructs into a dialectical interaction with theory and practice

A Bibliography for After Jews and Arabs

"Ammiel Alcalay’s groundbreaking work, After Jews and Arabs, published in 1993, redrew the geographic, political, cultural, and emotional map of relations between Jews and Arabs in the Levantine/Mediterranean world over a thousand-year period. Based on over a decade of research and fieldwork in many disciplines—including history and historiography; anthropology, ethnography, and ethnomusicology; political economy and geography; linguistics; philosophy; and the history of science and technology—the book presented a radically different perspective than that presented by received opinion. Given the radical and iconoclastic nature of Alcalay’s perspective, After Jews and Arabs met great resistance in attempts to publish it. Though completed and already circulating in 1989, it didn’t appear until 1993. In addition, when the book was published, there wasn’t enough space to include its original bibliography, a foundational part of the project. A Bibliography for After Jews and Arabs presents the original bibliography, as completed in 1992, without changes, as a glimpse into the historical record of a unique scholarly, political, poetic, and cultural journey. The bibliography itself had roots in research begun in the late 1970s and demonstrates a very wide arc. In addition to the bibliography, we include two accompanying texts here. In “Behind the Scenes: Before After Jews and Arabs,” Alcalay takes us behind the closed doors of the academic process, reprinting the original readers reports and his detailed rebuttals, and in “On a Bibliography for After Jews and Arabs,” Alcalay contextualizes his own path to the work he undertook, in methodological, historical, and political terms.

A Bibliography for After Jews and Arabs

"Ammiel Alcalay’s groundbreaking work, After Jews and Arabs, published in 1993, redrew the geographic, political, cultural, and emotional map of relations between Jews and Arabs in the Levantine/Mediterranean world over a thousand-year period. Based on over a decade of research and fieldwork in many disciplines—including history and historiography; anthropology, ethnography, and ethnomusicology; political economy and geography; linguistics; philosophy; and the history of science and technology—the book presented a radically different perspective than that presented by received opinion. Given the radical and iconoclastic nature of Alcalay’s perspective, After Jews and Arabs met great resistance in attempts to publish it. Though completed and already circulating in 1989, it didn’t appear until 1993. In addition, when the book was published, there wasn’t enough space to include its original bibliography, a foundational part of the project. A Bibliography for After Jews and Arabs presents the original bibliography, as completed in 1992, without changes, as a glimpse into the historical record of a unique scholarly, political, poetic, and cultural journey. The bibliography itself had roots in research begun in the late 1970s and demonstrates a very wide arc. In addition to the bibliography, we include two accompanying texts here. In “Behind the Scenes: Before After Jews and Arabs,” Alcalay takes us behind the closed doors of the academic process, reprinting the original readers reports and his detailed rebuttals, and in “On a Bibliography for After Jews and Arabs,” Alcalay contextualizes his own path to the work he undertook, in methodological, historical, and political terms.

Experimental study of scattering in atom- surface collisions with atom energies of the order of eV

Supersonic molecular beams applied to study of interactions of neutral-particle beams with solid surface