Inference with interference between units in an fMRI experiment of motor inhibition

An experimental unit is an opportunity to randomly apply or withhold a treatment. There is interference between units if the application of the treatment to one unit may also affect other units. In cognitive neuroscience, a common form of experiment presents a sequence of stimuli or requests for cognitive activity at random to each experimental subject and measures biological aspects of brain activity that follow these requests. Each subject is then many experimental units, and interference between units within an experimental subject is likely, in part because the stimuli follow one another quickly and in part because human subjects learn or become experienced or primed or bored as the experiment proceeds. We use a recent fMRI experiment concerned with the inhibition of motor activity to illustrate and further develop recently proposed methodology for inference in the presence of interference. A simulation evaluates the power of competing procedures.Comment: Published by Journal of the American Statistical Association at http://www.tandfonline.com/doi/full/10.1080/01621459.2012.655954 . R package cin (Causal Inference for Neuroscience) implementing the proposed method is freely available on CRAN at https://CRAN.R-project.org/package=ci

Candida albicans promotes invasion and colonisation of Candida glabrata in a reconstituted human vaginal epithelium

The principal aim of this study was to investigate the in vitro co-infection of a reconstituted human vaginal epithelium (RHVE) by Candida albicans and Candida glabrata. Methods The ability of both species to invade and colonise the RHVE was examined using species-specific peptide nucleic acid (PNA) probe hybridisation, confocal laser scanning microscopy (CLSM) and a novel qRT-PCR protocol for Candida quantification in the tissues. RHVE damage was evaluated by measuring lactate dehydrogenase (LDH) activity. Candida virulence gene expression (HWP1, ALS, EPA, PLB, PLD and SAP) was evaluated by quantitative RT-PCR. Results The results showed that whilst both species induced damage to the RHVE, this was notably less with C. glabrata. Interestingly, there was a significant increase in C. glabrata RHVE colonisation and invasiveness when it was added to the tissue with C. albicans. The extent of RHVE damage caused by the two species appeared to be primarily dependent on the process of invasion. Of the virulence genes assayed, HWP1, PLD1 and ALS3 were deemed to be most associated with pathogenicity in the model. Conclusions For the first time, we have demonstrated that the RHVE model coupled with specific tools of analysis, allows assessment of Candida colonisation and invasion in single and co-infection. Using this model we have demonstrated that C. albicans enhanced C. glabrata colonisation, invasion and tissue damage, which was also evidenced by the expression of virulence genes.We would like to thank Mrs Kath Allsopp for processing and sectioning tissue samples. This work was supported by the research grant SFRH/BD/72742/2010 from "Fundacao para a Ciencia e Tecnologia (FCT)", Portugal. This work was supported by the Programa Operacional, Fatores de competitividade - COMPETE and by national funds through FCT - Fundacao para a Ciencia e a Tecnologia on the scope of the projects FCT PTDC/EBB-EBI/120495/2010, PTDC/SAU-MIC/119069/2010, RECI/EBB-EBI/0179/2012 and PEst-OE/EQB/LA0023/2013. The authors thank the Project "Bio-Health - Biotechnology and Bioengineering approaches to improve health quality", Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER

The search for proton decay

Following a very brief description of the theoretical developments which motivated the search for proton decay, I shall describe one of these experiments (the IMB experiment) in some detail. Then I shall compare recent results from that experiment with those from other detectors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87399/2/321_1.pd

Are alcoholism treatments effective? The Project MATCH data

BACKGROUND: Project MATCH was the largest and most expensive alcoholism treatment trial ever conducted. The results were disappointing. There were essentially no patient-treatment matches, and three very different treatments produced nearly identical outcomes. These results were interpreted post hoc as evidence that all three treatments were quite effective. We re-analyzed the data in order to estimate effectiveness in relation to quantity of treatment. METHODS: This was a secondary analysis of data from a multisite clinical trial of alcohol dependent volunteers (N = 1726) who received outpatient psychosocial therapy. Analyses were confined to the primary outcome variables, percent days abstinent (PDA) and drinks per drinking day (DDD). Overall tests between treatment outcome and treatment quantity were conducted. Next, three specific groups were highlighted. One group consisted of those who dropped out immediately; the second were those who dropped out after receiving only one therapy session, and the third were those who attended 12 therapy sessions. RESULTS: Overall, a median of only 3% of the drinking outcome at follow-up could be attributed to treatment. However this effect appeared to be present at week one before most of the treatment had been delivered. The zero treatment dropout group showed great improvement, achieving a mean of 72 percent days abstinent at follow-up. Effect size estimates showed that two-thirds to three-fourths of the improvement in the full treatment group was duplicated in the zero treatment group. Outcomes for the one session treatment group were worse than for the zero treatment group, suggesting a patient self selection effect. Nearly all the improvement in all groups had occurred by week one. The full treatment group had improved in PDA by 62% at week one, and the additional 11 therapy sessions added only another 4% improvement. CONCLUSION: The results suggest that current psychosocial treatments for alcoholism are not particularly effective. Untreated alcoholics in clinical trials show significant improvement. Most of the improvement which is interpreted as treatment effect is not due to treatment. Part of the remainder appears to be due to selection effects

Cooperation in anonymous dynamic social networks

Abstract We study the extent to which cooperative behavior can be sustained in large, anonymous, evolving social networks. Individuals strategically form relationships under a social matching protocol and engage in prisoner's dilemma interactions with their partners. We characterize a class of equilibria that support cooperation as a stationary outcome. When cooperation is possible, its level is uniquely determined. While neither community enforcement nor contagion mechanisms have force in our setting, the endogenous dynamics of the social network imply that cooperation allows an individual to gradually accumulate a large network of profitable interactions, while defection results in social marginalization. Even as players become perfectly patient, equilibrium allows for full cooperation, only autarky, or the coexistence of cooperation and defection, depending on payoffs. Smaller levels of cooperation can be sustained by a form of exclusivity among cooperators. * We than

IMPACT: The Journal of the Center for Interdisciplinary Teaching and Learning. Volume 10, Issue 2, Summer 2021

Impact: The Journal of the Center for Interdisciplinary Teaching & Learning is a peer-reviewed, biannual online journal that publishes scholarly and creative non-fiction essays about the theory, practice, and assessment of interdisciplinary education. Impact is produced by the Center for Interdisciplinary Teaching & Learning at Boston University College of General Studies. Impact accepts submissions throughout the year and publishes issues in February and July. Please submit your essays for consideration at https:// citl.submittable.com/submit. Impact provides free and open access to all of its research publications. There is no charge to authors for publication, and the journal abides by a CC-BY license. Authors published in Impact retain copyright on their articles, except for any third-party images and other materials added by Impact, which are subject to copyright of their respective owners. Authors are therefore free to disseminate and re-publish their articles, subject to any requirements of third-party copyright owners and subject to the original publication being fully cited. Visitors may download and forward articles subject to the citation requirements; all copyright notices must be displayed. If readers want to search by journal subject they might use these words: education, graduate, undergraduate, interdisciplinary, disciplines, curriculum, higher education.The theme of this issue is interdisciplinary approaches to, or including, the sciences. STEM disciplines like chemistry, biology, physics, computer science, and math are often taught as separate and distinct from the humanities. The concept of STEAM (STEM + Arts) has attempted to make STEM subjects more interdisciplinary, allowing students to interact with the material from different perspectives. The essays in this issue explore unique ways to design and implement interdisciplinary curricula that combine sciences and humanities/arts

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

On Quality Control Measures in Genome-Wide Association Studies: A Test to Assess the Genotyping Quality of Individual Probands in Family-Based Association Studies and an Application to the HapMap Data

Allele transmissions in pedigrees provide a natural way of evaluating the genotyping quality of a particular proband in a family-based, genome-wide association study. We propose a transmission test that is based on this feature and that can be used for quality control filtering of genome-wide genotype data for individual probands. The test has one degree of freedom and assesses the average genotyping error rate of the genotyped SNPs for a particular proband. As we show in simulation studies, the test is sufficiently powerful to identify probands with an unreliable genotyping quality that cannot be detected with standard quality control filters. This feature of the test is further exemplified by an application to the third release of the HapMap data. The test is ideally suited as the final layer of quality control filters in the cleaning process of genome-wide association studies. It identifies probands with insufficient genotyping quality that were not removed by standard quality control filtering

The Yeast La Related Protein Slf1p Is a Key Activator of Translation during the Oxidative Stress Response

The mechanisms by which RNA-binding proteins control the translation of subsets of mRNAs are not yet clear. Slf1p and Sro9p are atypical-La motif containing proteins which are members of a superfamily of RNA-binding proteins conserved in eukaryotes. RIP-Seq analysis of these two yeast proteins identified overlapping and distinct sets of mRNA targets, including highly translated mRNAs such as those encoding ribosomal proteins. In paralell, transcriptome analysis of slf1Δ and sro9Δ mutant strains indicated altered gene expression in similar functional classes of mRNAs following loss of each factor. The loss of SLF1 had a greater impact on the transcriptome, and in particular, revealed changes in genes involved in the oxidative stress response. slf1Δ cells are more sensitive to oxidants and RIP-Seq analysis of oxidatively stressed cells enriched Slf1p targets encoding antioxidants and other proteins required for oxidant tolerance. To quantify these effects at the protein level, we used label-free mass spectrometry to compare the proteomes of wild-type and slf1Δ strains following oxidative stress. This analysis identified several proteins which are normally induced in response to hydrogen peroxide, but where this increase is attenuated in the slf1Δ mutant. Importantly, a significant number of the mRNAs encoding these targets were also identified as Slf1p-mRNA targets. We show that Slf1p remains associated with the few translating ribosomes following hydrogen peroxide stress and that Slf1p co-immunoprecipitates ribosomes and members of the eIF4E/eIF4G/Pab1p ‘closed loop’ complex suggesting that Slf1p interacts with actively translated mRNAs following stress. Finally, mutational analysis of SLF1 revealed a novel ribosome interacting domain in Slf1p, independent of its RNA binding La-motif. Together, our results indicate that Slf1p mediates a translational response to oxidative stress via mRNA-specific translational control

Report on the Depth Requirements for a Massive Detector at Homestake

This report provides the technical justification for locating a large detector underground in a US based Deep Underground Science and Engineering Laboratory. A large detector with a fiducial mass greater than 100 kTon will most likely be a multipurpose facility. The main physics justification for such a device is detection of accelerator generated neutrinos, nucleon decay, and natural sources of neutrinos such as solar, atmospheric and supernova neutrinos. The requirement on the depth of this detector will be guided by the rate of signals from these sources and the rate of backgrounds from cosmic rays over a very wide range of energies (from solar neutrino energies of 5 MeV to high energies in the range of hundreds of GeV). For the present report, we have examined the depth requirement for a large water Cherenkov detector and a liquid argon time projection chamber. There has been extensive previous experience with underground water Cherenkov detectors such as IMB, Kamioka, and most recently, Super-Kamiokande which has a fiducial mass of 22 kTon and a total mass of 50 kTon at a depth of 2700 meters-water-equivalent in a mountain. Projections for signal and background capability for a larger and deeper(or shallower) detectors of this type can be scaled from these previous detectors. The liquid argon time projection chamber has the advantage of being a very fine-grained tracking detector, which should provide enhanced capability for background rejection. We have based background rejection on reasonable estimates of track and energy resolution, and in some cases scaled background rates from measurements in water. In the current work we have taken the approach that the depth should be sufficient to suppress the cosmogenic background below predicted signal rates for either of the above two technologies. Nevertheless, it is also clear that the underground facility that we are examining must have a long life and will most likely be used either for future novel uses of the currently planned detectors or new technologies. Therefore the depth requirement also needs to be made on the basis of sound judgment regarding possible future use. In particular, the depth should be sufficient for any possible future use of these cavities or the level which will be developed for these large structures.Along with these physics justifications there are practical issues regarding the existing infrastructure at Homestake and also the stress characteristics of the Homestake rock formations. In this report we will examine the various depth choices at Homestake from the point of view of the particle and nuclear physics signatures of interest. We also have sufficient information about the existing infrastructure and the rock characteristics to narrow the choice of levels for the development of large cavities with long lifetimes. We make general remarks on desirable ground conditions for such large cavities and then make recommendations on how to start examining these levels to make a final choice. In the appendix we have outlined the initial requirements for the detectors. These requirements will undergo refinement during the course of the design. Finally, we strongly recommend that the geotechnical studies be commenced at the 4850 ft level, which we find to be the most suitable, in a timely manner