The Paradox of Breadth: The Tension between Experience and Legitimacy in the Transition to Entrepreneurship

In a study of artists who launched independent record labels in the music industry from 1990 to 2013, we focus on explaining the paradox generated when prospective entrepreneurs accumulate broad functional experience, which signals to resource providers mastery of different skills and access to various information and resources but may also undermine the legitimacy of their entrepreneurial claims because they are not seen as specialists. To resolve this paradox, we theorize that the potential legitimacy discount of categorical membership can be avoided when individuals are classified according to multiple categories simultaneously. We find that the transition to entrepreneurship is most likely to occur when an artist’s functional experience is broad but market experience is narrow: he or she has mastered a variety of skills but solicited few audiences. We also find that the paradox of breadth is attenuated—the potential penalty of functional breadth and the corresponding need to develop narrow market experience are reduced—when the entrepreneur has alternate methods of signaling legitimacy, including high status and more-typical prior work experience. Moreover, some audiences are more disposed than others to allow an entrepreneur to pursue greater novelty. Our findings suggest that mastering a variety of skills is not universally beneficial for aspiring entrepreneurs. In some circumstances, such mastery is best coupled with a narrow market focus

QCD corrections to stoponium production at hadron colliders

If the lighter top squark has no kinematically allowed two-body decays that conserve flavor, then it will live long enough to form hadronic bound states. The observation of the diphoton decays of stoponium could then provide a uniquely precise measurement of the top squark mass. In this paper, we calculate the cross section for the production of stoponium in a hadron collider at next-to-leading order (NLO) in QCD. We present numerical results for the cross section for production of stoponium at the LHC and study the dependence on beam energy, stoponium mass, and the renormalization and factorization scale. The cross-section is substantially increased by the NLO corrections, counteracting a corresponding decrease found earlier in the NLO diphoton branching ratio.Comment: 24 page

A founding penalty: evidence from an audit study on gender, entrepreneurship, and future employment

Whereas much research has focused on the benefits of an entrepreneurial career, less attention has been devoted to understanding its costs. In particular, studies have left unanswered the question of how employers evaluate ex-founders at the point of hire. We propose that employers penalize job candidates with a history of entrepreneurship because they believe them to be less competent and worse fits than comparable candidates without founding experience. However, we also argue that this penalty is mitigated for women. Because women are often perceived as illegitimate founders, employers do not treat their entrepreneurial efforts as revealing unwanted attributes and are correspondingly more likely to hire them than male ex-founders. We find evidence in support of these claims with data from a resume-based audit and an experimental survey of Marketing and HR professionals. Our results show that employers evaluate ex-founders negatively, perceiving them as less fit and less competent prospective employees. However, we also find that this penalty does not attach for female ex-founders because future employers do not associate them with the same entrepreneurial attributes that reduce hiring chances

Non-universal gaugino masses, the supersymmetric little hierarchy problem, and dark matter

We study a class of supersymmetric models with non-universal gaugino masses that could arise from F-terms in a general combination of the singlet and adjoint representations of SU(5). We explore models that satisfy present Large Hadron Collider and other bounds, showing how the allowed parameter space is divided into distinct "continents". Regions of parameter space that ameliorate the supersymmetric little hierarchy problem with a small mu parameter include the usual focus point scenario, but also natural areas with much lighter squarks and sleptons. These models are continuously connected in parameter space to regions in which stau co-annihilation or Higgs exchange is mostly responsible for dark matter annihilation, and to models in which the thermal relic abundance is achieved by slepton-mediated annihilation, reviving the bulk region that is severely restricted in mSUGRA models. In hybrid or confluence regions, several mechanisms combine to give the requisite dark matter annihilation rate. In each case we study the prospects for direct detection of dark matter. We also comment briefly on the impact of recent hints for M_h near 125 GeV from the LHC.Comment: 24 pages. v2: references and minor comments adde

Systematic evaluation of the impact of ChIP-seq read designs on genome coverage, peak identification, and allele-specific binding detection

Background: Chromatin immunoprecipitation followed by sequencing (ChIP-seq) experiments revolutionized genome-wide profiling of transcription factors and histone modifications. Although maturing sequencing technologies allow these experiments to be carried out with short (36–50 bps), long (75–100 bps), single-end, or paired-end reads, the impact of these read parameters on the downstream data analysis are not well understood. In this paper, we evaluate the effects of different read parameters on genome sequence alignment, coverage of different classes of genomic features, peak identification, and allele-specific binding detection. Results: We generated 101 bps paired-end ChIP-seq data for many transcription factors from human GM12878 and MCF7 cell lines. Systematic evaluations using in silico variations of these data as well as fully simulated data, revealed complex interplay between the sequencing parameters and analysis tools, and indicated clear advantages of paired-end designs in several aspects such as alignment accuracy, peak resolution, and most notably, allele-specific binding detection. Conclusions: Our work elucidates the effect of design on the downstream analysis and provides insights to investigators in deciding sequencing parameters in ChIP-seq experiments. We present the first systematic evaluation of the impact of ChIP-seq designs on allele-specific binding detection and highlights the power of pair-end designs in such studies

In Vivo Measurement of Cerebral Mitochondrial Metabolism Using Broadband Near Infrared Spectroscopy Following Neonatal Stroke

Neonatal stroke presents with features of encephalopathy and can result in significant morbidity and mortality. We investigated the cerebral metabolic and haemodynamic changes following neonatal stroke in a term infant at 24 h of life. Changes in oxidation state of cytochrome-c-oxidase (oxCCO) concentration were monitored along with changes in oxy- and deoxy- haemoglobin using a new broadband near-infrared spectroscopy (NIRS) system. Repeated transient changes in cerebral haemodynamics and metabolism were noted over a 3-h study period with decrease in oxyhaemoglobin (HbO2), deoxy haemoglobin (HHb) and oxCCO in both cerebral hemispheres without significant changes in systemic observations. A clear asymmetry was noted in the degree of change between the two cerebral hemispheres. Changes in cerebral oxygenation (measured as HbDiff=HbO2-HHb) and cerebral metabolism (measured as oxCCO) were highly coupled on the injured side of the brain

A tool for assessing the climate change mitigation and health impacts of environmental policies: the Cities Rapid Assessment Framework for Transformation (CRAFT) [version 2; peer review: 3 approved]

Background: A growing number of cities, including Greater London, have set ambitious targets, including detailed policies and implementation plans, to reach global goals on sustainability, health, and climate change. Here we present a tool for a rapid assessment of the magnitude of impact of specific policy initiatives to reach these targets. The decision-support tool simultaneously quantifies the environmental and health impacts of specified selected policies. Methods: The ‘Cities Rapid Assessment Framework for Transformation (CRAFT)’ tool was applied to Greater London. CRAFT quantifies the effects of ten environmental policies on changes in (1) greenhouse gas (GHG) emissions, (2) exposures to environmental hazards, (3) travel-related physical activity, and (4) mortality (the number of attributable deaths avoided in one typical year). Publicly available data and epidemiological evidence were used to make rapid quantitative estimates of these effects based on proportional reductions in GHG emissions and environmental exposures from current baseline levels and to compute the mortality impacts. Results: The CRAFT tool estimates that, of roughly 50,000 annual deaths in Greater London, the modelled hazards (PM2.5 (from indoor and outdoor sources), outdoor NO2, indoor radon, cold, overheating) and low travel-related physical activity are responsible for approximately 10,000 premature environment-related deaths. Implementing the selected polices could reduce the annual mortality number by about 20% (~1,900 deaths) by 2050. The majority of these deaths (1,700) may be avoided through increased uptake in active travel. Thus, out of ten environmental policies, the ‘active travel’ policy provides the greatest health benefit. Also, implementing the ten policies results in a GHG reduction of around 90%. Conclusions: The CRAFT tool quantifies the effects of city policies on reducing GHG emissions, decreasing environmental health hazards, and improving public health. The tool has potential value for policy makers through providing quantitative estimates of health impacts to support and prioritise policy options

Systematic evaluation of the impact of ChIP-seq read designs on genome coverage, peak identification, and allele-specific binding detection

Background: Chromatin immunoprecipitation followed by sequencing (ChIP-seq) experiments revolutionized genome-wide profiling of transcription factors and histone modifications. Although maturing sequencing technologies allow these experiments to be carried out with short (36–50 bps), long (75–100 bps), single-end, or paired-end reads, the impact of these read parameters on the downstream data analysis are not well understood. In this paper, we evaluate the effects of different read parameters on genome sequence alignment, coverage of different classes of genomic features, peak identification, and allele-specific binding detection. Results: We generated 101 bps paired-end ChIP-seq data for many transcription factors from human GM12878 and MCF7 cell lines. Systematic evaluations using in silico variations of these data as well as fully simulated data, revealed complex interplay between the sequencing parameters and analysis tools, and indicated clear advantages of paired-end designs in several aspects such as alignment accuracy, peak resolution, and most notably, allele-specific binding detection. Conclusions: Our work elucidates the effect of design on the downstream analysis and provides insights to investigators in deciding sequencing parameters in ChIP-seq experiments. We present the first systematic evaluation of the impact of ChIP-seq designs on allele-specific binding detection and highlights the power of pair-end designs in such studies

LRRTM3 Interacts with APP and BACE1 and Has Variants Associating with Late-Onset Alzheimer's Disease (LOAD)

Leucine rich repeat transmembrane protein 3 (LRRTM3) is member of a synaptic protein family. LRRTM3 is a nested gene within α-T catenin (CTNNA3) and resides at the linkage peak for late-onset Alzheimer’s disease (LOAD) risk and plasma amyloid β (Aβ) levels. In-vitro knock-down of LRRTM3 was previously shown to decrease secreted Aβ, although the mechanism of this is unclear. In SH-SY5Y cells overexpressing APP and transiently transfected with LRRTM3 alone or with BACE1, we showed that LRRTM3 co-localizes with both APP and BACE1 in early endosomes, where BACE1 processing of APP occurs. Additionally, LRRTM3 co-localizes with APP in primary neuronal cultures from Tg2576 mice transduced with LRRTM3-expressing adeno-associated virus. Moreover, LRRTM3 co-immunoprecipitates with both endogenous APP and overexpressed BACE1, in HEK293T cells transfected with LRRTM3. SH-SY5Y cells with knock-down of LRRTM3 had lower BACE1 and higher CTNNA3 mRNA levels, but no change in APP. Brain mRNA levels of LRRTM3 showed significant correlations with BACE1, CTNNA3 and APP in ∼400 humans, but not in LRRTM3 knock-out mice. Finally, we assessed 69 single nucleotide polymorphisms (SNPs) within and flanking LRRTM3 in 1,567 LOADs and 2,082 controls and identified 8 SNPs within a linkage disequilibrium block encompassing 5′UTR-Intron 1 of LRRTM3 that formed multilocus genotypes (MLG) with suggestive global association with LOAD risk (p = 0.06), and significant individual MLGs. These 8 SNPs were genotyped in an independent series (1,258 LOADs and 718 controls) and had significant global and individual MLG associations in the combined dataset (p = 0.02–0.05). Collectively, these results suggest that protein interactions between LRRTM3, APP and BACE1, as well as complex associations between mRNA levels of LRRTM3, CTNNA3, APP and BACE1 in humans might influence APP metabolism and ultimately risk of AD.© 2013 Lincoln et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited