Understanding the Revenue Potential of Tax Compliance Investment

In a July 2020 report, the Congressional Budget Office estimated that modest investments in the IRS would generate somewhere between $60 and$100 billion in additional revenue over a decade. This is qualitatively correct. But quantitatively, the revenue potential is much more significant than the CBO report suggests. We highlight five reasons for the CBO’s underestimation: 1) the scale of the investment in the IRS contemplated is modest and far short of sufficient even to return the IRS budget to 2011 levels; 2) the CBO contemplates a limited range of interventions, excluding entirely progress on information reporting and technological advancements; 3) the estimates assume rapidly diminishing returns to marginal increases in investment; 4) the estimates leave out the effect of increased enforcement on taxpayer decision-making; and 5) the use of the 10-year window means that the long-run benefits of increased enforcement are excluded. We discuss these issues, present an alternative calculation, and conclude that a commitment to restoring tax compliance efforts to historical levels could generate over $1 trillion in the next decade

Protease inhibitors selectively block T cell receptor-triggered programmed cell death in a murine T cell hybridoma and activated peripheral T cells.

The hypothesis that cytoplasmic proteases play a functional role in programmed cell death was tested by examining the effect of protease inhibitors on the T cell receptor-mediated death of the 2B4 murine T cell hybridoma and activated T cells. The cysteine protease inhibitors trans-epoxysuccininyl-L-leucylamido-(4-guanidino) butane (E-64) and leupeptin, the calpain selective inhibitor acetyl-leucyl-leucyl-normethional, and the serine protease inhibitors diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride, all showed dose-dependent blocking of the 2B4 death response triggered by the T cell receptor complex and by anti-Thy-1. These protease inhibitors enhanced rather than inhibited IL-2 secretion triggered by T cell receptor cross-linking, showing that they did not act by preventing signal transduction. Growth inhibition induced by cross-linking the 2B4 T cell receptor, measured by inhibition of thymidine incorporation, was not generally blocked by these protease inhibitors. All five of these protease inhibitors enhanced rather than blocked 2B4 cell death triggered by dexamethasone, an agent previously shown to have a death pathway antagonistic with that of the TCR. 2B4 cytolysis by the cytotoxic agents staphylococcal α-toxin and dodecyl imidazole, and that caused by hypotonic conditions, was not significantly affected by the five protease inhibitors tested. The selected protease inhibitors blocked both the apoptotic nuclear morphology changes and DNA fragmentation induced by T cell receptor cross-linking, and enhanced both these properties induced by dexamethasone in 2B4 cells. The T cell receptor-induced death of activated murine lymph node T cells and human peripheral blood CD4+ T cells was blocked by both cysteine and serine protease inhibitors, showing that the protease-dependent death pathway also operates in these systems

Comparing Platforms for C. elegans Mutant Identification Using High-Throughput Whole-Genome Sequencing

Whole-genome sequencing represents a promising approach to pinpoint chemically induced mutations in genetic model organisms, thereby short-cutting time-consuming genetic mapping efforts.We compare here the ability of two leading high-throughput platforms for paired-end deep sequencing, SOLiD (ABI) and Genome Analyzer (Illumina; "Solexa"), to achieve the goal of mutant detection. As a test case we used a mutant C. elegans strain that harbors a mutation in the lsy-12 locus which we compare to the reference wild-type genome sequence. We analyzed the accuracy, sensitivity, and depth-coverage characteristics of the two platforms. Both platforms were able to identify the mutation that causes the phenotype of the mutant C. elegans strain, lsy-12. Based on a 4 MB genomic region in which individual variants were validated by Sanger sequencing, we observe tradeoffs between rates of false positives and false negatives when using both platforms under similar coverage and mapping criteria.In conclusion, whole-genome sequencing conducted by either platform is a viable approach for the identification of single-nucleotide variations in the C. elegans genome

C. elegans mutant identification with a one-step whole-genome-sequencing and SNP mapping strategy.

Whole-genome sequencing (WGS) is becoming a fast and cost-effective method to pinpoint molecular lesions in mutagenized genetic model systems, such as Caenorhabditis elegans. As mutagenized strains contain a significant mutational load, it is often still necessary to map mutations to a chromosomal interval to elucidate which of the WGS-identified sequence variants is the phenotype-causing one. We describe here our experience in setting up and testing a simple strategy that incorporates a rapid SNP-based mapping step into the WGS procedure. In this strategy, a mutant retrieved from a genetic screen is crossed with a polymorphic C. elegans strain, individual F2 progeny from this cross is selected for the mutant phenotype, the progeny of these F2 animals are pooled and then whole-genome-sequenced. The density of polymorphic SNP markers is decreased in the region of the phenotype-causing sequence variant and therefore enables its identification in the WGS data. As a proof of principle, we use this strategy to identify the molecular lesion in a mutant strain that produces an excess of dopaminergic neurons. We find that the molecular lesion resides in the Pax-6/Eyeless ortholog vab-3. The strategy described here will further reduce the time between mutant isolation and identification of the molecular lesion

Impulsivity and approach tendencies towards cigarette stimuli: Implications for cigarette smoking and cessation behaviors among youth

Impulsivity is associated with smoking, difficulties quitting smoking, and approach tendencies toward cigarette stimuli among adolescents. We examined the effects of impulsivity on (a) the association between approach tendencies and adolescents’ smoking status and (b) the effectiveness of Cognitive Bias Modification (CBM), a smoking cessation intervention focused on changing approach tendencies, among adolescent smokers. We conducted a secondary analysis of evidence from 2 previous published studies: Study 1: a cross-sectional study comparing impulsivity and approach tendencies between adolescent smokers (n = 67) and nonsmokers (n = 58); Study 2: a treatment study that randomized 60 adolescent smokers to receive either CBM or sham training. Impulsivity was measured using the Barratt Impulsiveness Scale (BIS) and the Experiential Discounting Task (EDT). We found higher impulsivity, as determined by the BIS but not the EDT, increased adolescents’ odds of being smokers. We observed that the interaction between EDT and approach tendencies also significantly predicted smoking status, however post hoc comparisons were not significant. Adolescents with higher BIS scores receiving CBM had increased odds of being abstinent at the end of treatment, but we found no association between EDT and treatment outcome. Our findings suggest that approach-bias modification (a form of CBM) may be more effective in impulsive adolescent smokers. Differences in findings for BIS and EDT highlight the complexity of the construct of impulsivity. Future studies with larger samples are needed to further disentangle the effects of different aspects of impulsivity on smoking behaviors and cessation outcomes among youth

Diamond pixel detector for beam profile monitoring in COMET experiment at J-PARC

We present the design and initial prototype results of a pixellized proton beam profile monitor for the COMET experiment at J-PARC. The goal of COMET is to look for charged lepton flavor violation by direct muon to electron conversion at a sensitivity of $0^{-19}$. An 8 GeV proton beam pulsed at 100 ns with $10^{10}$ protons/s will be used to create muons through pion production and decay. In the final experiment, the proton flux will be raised to $10^{14}$ protons/sec to increase the sensitivity. These requirements of harsh radiation tolerance and fast readout make diamond a good choice for constructing a beam profile monitor in COMET. We present first results of the characterization of single crystal diamond (scCVD) sourced from a new company, 2a systems Singapore. Our measurements indicate excellent charge collection efficiency and high carrier mobility down to cryogenic temperatures.Comment: Pixel 2014 Workshop proceedings in JINS

Differential effects of nanoselenium doping on healthy and cancerous osteoblasts in coculture on titanium

In the present study, selenium (Se) nanoclusters were grown through heterogeneous nucleation on titanium (Ti) surfaces, a common orthopedic implant material. Normal healthy osteoblasts (bone-forming cells) and cancerous osteoblasts (osteosarcoma) were cultured on the Se-doped surfaces having three different coating densities. For the first time, it is shown that substrates with Se nanoclusters promote normal osteoblast proliferation and inhibit cancerous osteoblast growth in both separate (mono-culture) and coculture experiment. This study suggests that Se surface nanoclusters can be properly engineered to inhibit bone cancer growth while simultaneously promoting the growth of normal bone tissue

Ambiguity and public good provision in large societies

ArticleIn this paper, we consider the effect of ambiguity on the private provision of public goods. Equilibrium is shown to exist and be unique. We examine how provision of the public good changes as the size of the population increases. We show that when there is uncertainty, there may be less free-riding in large societies

The PGE2-Stat3 interaction in doxorubicin-induced myocardial apoptosis

Aims Both cyclooxygenase-2 (COX-2) and the transcription factor signal transducer and activator of transcription 3 (Stat3) are involved in adaptive growth and survival of cardiomyocytes. In ventricular cardiomyocytes, prostaglandin E2 (PGE2), a major COX-2 product, leads to adaptive growth via Stat3 activation, but whether this transcription factor acts as a signalling molecule in PGE2-induced cell survival is unknown. Therefore, the purpose of this study was to determine whether PGE2 counteracts cardiac apoptosis induced by doxorubicin (DOX), and if so, whether Stat3 plays a critical role in this cardioprotective effect. Methods and results Neonatal rat ventricular cardiomyocytes were incubated with DOX (0.5 µM) and/or PGE2 (1 µM). Apoptosis was assessed by determining caspase3 activation and apoptotic DNA fragmentation. The role of Stat3 was evaluated in vitro and in vivo by transfecting cardiomyocytes with siRNA targeting rat Stat3 and by using cardiomyocyte-restricted Stat3 knockout (Stat3 KO) mice, respectively. Incubation of ventricular cardiomyocytes with PGE2 led to a time-dependent decrease in the DOX-induced caspase3 activation, reaching a maximal inhibition of 70 ± 5% after 4 h. Similarly, PGE2 inhibited DOX-induced DNA fragmentation by 58 ± 5% after 24 h. This antiapoptotic action of PGE2 was strongly reduced by the ERK1/2 inhibitor, U0126, whereas the p38 MAP kinase inhibitor, SB203580, had no effect. Depleting Stat3 expression by 50-60% in isolated ventricular cardiomyocytes markedly reduced the protective effect of PGE2 on DOX-induced caspase3 activation and DNA fragmentation. Likewise, the stable PGE2 analogue, 16,16-dimethyl-PGE2, was unable to counteract cardiac apoptosis induced by DOX in Stat3 KO mice. Conclusion Our results demonstrate that PGE2 prevents myocardial apoptosis induced by DOX. This protection requires the activation of the prosurvival pathways of Stat3 and ERK1/