Life's a Balancing Act: How Men and Women Experience the Work-Home Interface across the Life Course.

As women, and particularly mothers, have increased their labor force participation in the last half-century, and as the expectation for men to spend more time in childcare and housework has increased, more men and women now must combine role responsibilities in the work and home domains than ever before. Using quantitative and qualitative data, this dissertation takes a sociological approach to understanding the variation in experiences at the work-home interface that have arisen in this time of substantial social change. In assessing how taking on work-home roles can influence individual outcomes, I show that it is important to consider both within- and between-gender differences at the work-home interface, and highlight the utility of applying a life course perspective to work-family research. The first empirical chapter uses two waves of a national sample of working adults to document how transitions in family roles are related to perceptions of work spilling over into home, and home spilling over into work, and how these associations differ by gender. This chapter provides evidence that taking on dual work-home role responsibilities can produce both role strain and role enhancement, laying the groundwork for future studies of how strain and enhancement might combine rather than compete. The second empirical chapter uses data from qualitative interviews with medical trainees to show how competing devotions to work, family, and personal lives shape the way important career decisions are made. The third empirical chapter uses nationally-representative and longitudinal data to document the association between working, parenting, and long-term health trajectories. Taken together, these studies suggest that social policy agendas should consider the ways in which work and home domains are linked, as well as focus on important turning points across the life course. Policy efforts to mitigate gender inequality in the labor force would do well to continue to push for gender-neutral work-family policies, as it is clear that conflict at the work-home interface is not a solely female experience, and that both men and women navigate and seek solutions for complex work-home dilemmas across the life course.PhDSociologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113444/1/linkathy_1.pd

Effect of Primordial Black Holes on the Cosmic Microwave Background and Cosmological Parameter Estimates

We investigate the effect of non-evaporating primordial black holes (PBHs) on the ionization and thermal history of the universe. X-rays emitted by gas accretion onto PBHs modify the cosmic recombination history, producing measurable effects on the spectrum and anisotropies of the Cosmic Microwave Background (CMB). Using the third-year WMAP data and FIRAS data we improve existing upper limits on the abundance of PBHs with masses >0.1 Msun by several orders of magnitude. Fitting WMAP3 data with cosmological models that do not allow for non-standard recombination histories, as produced by PBHs or other early energy sources, may lead to an underestimate of the best-fit values of the amplitude of linear density fluctuations (sigma_8) and the scalar spectral index (n_s). Cosmological parameter estimates are affected because models with PBHs allow for larger values of the Thomson scattering optical depth, whose correlation with other parameters may not be correctly taken into account when PBHs are ignored. Values of tau_e=0.2, n_s=1 and sigma_8=0.9 are allowed at 95% CF. This result that may relieve recent tension between WMAP3 data and clusters data on the value of sigma_8. PBHs may increase the primordial molecular hydrogen abundance by up to two orders of magnitude, this promoting cooling and star formation. The suppression of galaxy formation due to X-ray heating is negligible for models consistent with the CMB data. Thus, the formation rate of the first galaxies and stars would be enhanced by a population of PBHs.Comment: 17 pages (Apj style), 9 figures, submitted to Ap

Association study of genetic variation in DNA repair pathway genes and risk of basal cell carcinoma

DNA repair plays a critical role in protecting the genome from ultraviolet radiation and maintaining the genomic integrity of cells. Genetic variants in DNA repair-related genes can influence an individual's DNA repair capacity, which may be related to the risk of developing basal cell carcinoma (BCC). We comprehensively assessed the associations of 2,965 independent single-nucleotide polymorphisms (SNPs) across 165 DNA repair pathway genes with BCC risk in a genome-wide association meta-analysis totaling 17,187 BCC cases and 287,054 controls from two data sets. After multiple testing corrections, we identified three SNPs (rs2805831 upstream of XPA: OR = 0.93, P = 1.35 × 10-6 ; rs659857 in exon of MUS81: OR = 1.06, P = 3.09 × 10-6 and rs57343616 in 3' UTR of NABP2: OR = 1.11, P = 6.47 × 10-6 ) as significantly associated with BCC risk in meta-analysis, and all of them were nominally significant in both data sets. Furthermore, rs659857 [T] was significantly associated with decreased expression of MUS81 mRNA in the expression quantitative trait locus (eQTL) analysis. Our findings suggest that the inherited common variation in three DNA repair genes-XPA, MUS81 and NABP2-may be involved in the development of BCC. To our knowledge, our study is the first report thoroughly examining the effects of SNPs across DNA repair pathway genes on BCC risk based on a genome-wide association meta-analysis

Aligned electrospun nanofibers specify the direction of dorsal root ganglia neurite growth

Nerve injury, a significant cause of disability, may be treated more effectively using nerve guidance channels containing longitudinally aligned fibers. Aligned, electrospun nanofibers direct the neurite growth of immortalized neural stem cells, demonstrating potential for directing regenerating neurites. However, no study of neurite guidance on these fibers has yet been performed with primary neurons. Here, we examined neurites from dorsal root ganglia explants on electrospun poly- L -lactate nanofibers of high, intermediate, and random alignment. On aligned fibers, neurites grew radially outward from the ganglia and turned to follow the fibers upon contact. Neurite guidance was robust, with neurites never leaving the fibers to grow on the surrounding cover slip. To compare the alignment of neurites to that of the nanofiber substrates, Fourier methods were used to quantify the alignment. Neurite alignment, however striking, was inferior to fiber alignment on all but the randomly aligned fibers. Neurites on highly aligned substrates were 20 and 16% longer than neurites on random and intermediate fibers, respectively. Schwann cells on fibers assumed a very narrow morphology compared to those on the surrounding coverslip. The robust neurite guidance demonstrated here is a significant step toward the use of aligned, electrospun nanofibers for nerve regeneration. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57401/1/31285_ftp.pd

The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling

Antibiotic therapy, especially when administered long term, is associated with adverse hematologic effects such as cytopenia. Signals from the intestinal microbiota are critical to maintain normal hematopoiesis, and antibiotics can cause bone marrow suppression through depletion of the microbiota. We reported previously that STAT1 signaling is necessary for microbiota-dependent hematopoiesis, but the precise mechanisms by which the gut microbiota signals to the host bone marrow to regulate hematopoiesis remain undefined. We sought to identify the cell type(s) through which STAT1 promotes microbiota-mediated hematopoiesis and to elucidate which upstream signaling pathways trigger STAT1 signaling. Using conditional knockout and chimeric mice, we found that the microbiota induced STAT1 signaling in non-myeloid hematopoietic cells to support hematopoiesis and that STAT1 signaling was specifically dependent on type I interferons (IFNs). Indeed, basal type I IFN signaling was reduced in hematopoietic progenitor cells with antibiotic treatment. In addition, we discovered that oral administration of a commensal-derived product, NOD1 ligand, rescues the hematopoietic defects induced by antibiotics in mice. Using metabolomics, we identified additional microbially produced candidates that can stimulate type I IFN signaling to potentially rescue the hematopoietic defects induced by antibiotics, including phosphatidylcholine and γ-glutamylalanine. Overall, our studies define a signaling pathway through which microbiota promotes normal hematopoiesis and identify microbial metabolites that may serve as therapeutic agents to ameliorate antibiotic-induced bone marrow suppression and cytopenia

Surprisingly Simple Spectra

The large N limit of the anomalous dimensions of operators in ${\cal N}=4$ super Yang-Mills theory described by restricted Schur polynomials, are studied. We focus on operators labeled by Young diagrams that have two columns (both long) so that the classical dimension of these operators is O(N). At large N these two column operators mix with each other but are decoupled from operators with $n\ne 2$ columns. The planar approximation does not capture the large N dynamics. For operators built with 2, 3 or 4 impurities the dilatation operator is explicitly evaluated. In all three cases, in a certain limit, the dilatation operator is a lattice version of a second derivative, with the lattice emerging from the Young diagram itself. The one loop dilatation operator is diagonalized numerically. All eigenvalues are an integer multiple of $8g_{YM}^2$ and there are interesting degeneracies in the spectrum. The spectrum we obtain for the one loop anomalous dimension operator is reproduced by a collection of harmonic oscillators. This equivalence to harmonic oscillators generalizes giant graviton results known for the BPS sector and further implies that the Hamiltonian defined by the one loop large $N$ dilatation operator is integrable. This is an example of an integrable dilatation operator, obtained by summing both planar and non-planar diagrams.Comment: 34 page

Topoisomerase 1 Inhibition in MYC-Driven Cancer Promotes Aberrant R-Loop Accumulation to Induce Synthetic Lethality

CRISPR screening reveals topoisomerase 1 as an immediately actionable vulnerability in cancers harboring MYC as a driver oncoprotein that can be targeted with clinically approved inhibitors. MYC is a central regulator of gene transcription and is frequently dysregulated in human cancers. As targeting MYC directly is challenging, an alternative strategy is to identify specific proteins or processes required for MYC to function as a potent cancer driver that can be targeted to result in synthetic lethality. To identify potential targets in MYC-driven cancers, we performed a genome-wide CRISPR knockout screen using an isogenic pair of breast cancer cell lines in which MYC dysregulation is the switch from benign to transformed tumor growth. Proteins that regulate R-loops were identified as a potential class of synthetic lethal targets. Dysregulated MYC elevated global transcription and coincident R-loop accumulation. Topoisomerase 1 (TOP1), a regulator of R-loops by DNA topology, was validated to be a vulnerability in cells with high MYC activity. Genetic knockdown of TOP1 in MYC-transformed cells resulted in reduced colony formation compared with control cells, demonstrating synthetic lethality. Overexpression of RNaseH1, a riboendonuclease that specifically degrades R-loops, rescued the reduction in clonogenicity induced by TOP1 deficiency, demonstrating that this vulnerability is driven by aberrant R-loop accumulation. Genetic and pharmacologic TOP1 inhibition selectively reduced the fitness of MYC-transformed tumors in vivo. Finally, drug response to TOP1 inhibitors (i.e., topotecan) significantly correlated with MYC levels and activity across panels of breast cancer cell lines and patient-derived organoids. Together, these results highlight TOP1 as a promising target for MYC-driven cancers.Significance: CRISPR screening reveals topoisomerase 1 as an immediately actionable vulnerability in cancers harboring MYC as a driver oncoprotein that can be targeted with clinically approved inhibitors

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations

Molecular identification of adenoviruses associated with respiratory infection in Egypt from 2003 to 2010.

BACKGROUND: Human adenoviruses of species B, C, and E (HAdV-B, -C, -E) are frequent causative agents of acute respiratory infections worldwide. As part of a surveillance program aimed at identifying the etiology of influenza-like illness (ILI) in Egypt, we characterized 105 adenovirus isolates from clinical samples collected between 2003 and 2010. METHODS: Identification of the isolates as HAdV was accomplished by an immunofluorescence assay (IFA) and confirmed by a set of species and type specific polymerase chain reactions (PCR). RESULTS: Of the 105 isolates, 42% were identified as belonging to HAdV-B, 60% as HAdV-C, and 1% as HAdV-E. We identified a total of six co-infections by PCR, of which five were HAdV-B/HAdV-C co-infections, and one was a co-infection of two HAdV-C types: HAdV-5/HAdV-6. Molecular typing by PCR enabled the identification of eight genotypes of human adenoviruses; HAdV-3 (n = 22), HAdV-7 (n = 14), HAdV-11 (n = 8), HAdV-1 (n = 22), HAdV-2 (20), HAdV-5 (n = 15), HAdV-6 (n = 3) and HAdV-4 (n = 1). The most abundant species in the characterized collection of isolates was HAdV-C, which is concordant with existing data for worldwide epidemiology of HAdV respiratory infections. CONCLUSIONS: We identified three species, HAdV-B, -C and -E, among patients with ILI over the course of 7 years in Egypt, with at least eight diverse types circulating

Probing EWSB Naturalness in Unified SUSY Models with Dark Matter

We have studied Electroweak Symmetry Breaking (EWSB) fine-tuning in the context of two unified Supersymmetry scenarios: the Constrained Minimal Supersymmetric Model (CMSSM) and models with Non-Universal Higgs Masses (NUHM), in light of current and upcoming direct detection dark matter experiments. We consider both those models that satisfy a one-sided bound on the relic density of neutralinos, $\Omega_{\chi} h^2 < 0.12$, and also the subset that satisfy the two-sided bound in which the relic density is within the 2 sigma best fit of WMAP7 + BAO + H0 data. We find that current direct detection searches for dark matter probe the least fine-tuned regions of parameter-space, or equivalently those of lowest Higgs mass parameter $\mu$, and will tend to probe progressively more and more fine-tuned models, though the trend is more pronounced in the CMSSM than in the NUHM. Additionally, we examine several subsets of model points, categorized by common mass hierarchies; M_{\chi_0} \sim M_{\chi^\pm}, M_{\chi_0} \sim M_{\stau}, M_{\chi_0} \sim M_{\stop_1}, the light and heavy Higgs poles, and any additional models classified as "other"; the relevance of these mass hierarchies is their connection to the preferred neutralino annihilation channel that determines the relic abundance. For each of these subsets of models we investigated the degree of fine-tuning and discoverability in current and next generation direct detection experiments.Comment: 26 pages, 10 figures. v2: references added. v3: matches published versio