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Many cellular processes occur out of equilibrium. This includes site-specific unwinding in supercoiled DNA, which may play an important role in gene regulation. Here, we use the Convex Lens-induced Confinement (CLiC) single-molecule microscopy platform to study these processes with high-throughput and without artificial constraints on molecular structures or interactions. We use two model DNA plasmid systems, pFLIP-FUSE and pUC19, to study the dynamics of supercoiling-induced secondary structural transitions after perturbations away from equilibrium. We find that structural transitions can be slow, leading to long-lived structural states whose kinetics depend on the duration and direction of perturbation. Our findings highlight the importance of out-of-equilibrium studies when characterizing the complex structural dynamics of DNA and understanding the mechanisms of gene regulation.

A panoply of new tools for tracking single particles and molecules has led to an explosion of experimental data, leading to novel insights into physical properties of living matter governing cellular development and function, health and disease. In this Perspective, we present tools to investigate the dynamics and mechanics of living systems from the molecular to cellular scale via single-particle techniques. In particular, we focus on methods to measure, interpret, and analyse complex data sets that are associated with forces, materials properties, transport, and emergent organisation phenomena within biological and soft-matter systems. Current approaches, challenges, and existing solutions in the associated fields are outlined in order to support the growing community of researchers at the interface of physics and the life sciences. Each section focuses not only on the general physical principles and the potential for understanding living matter, but also on details of practical data extraction and analysis, discussing limitations, interpretation, and comparison across different experimental realisations and theoretical frameworks. Particularly relevant results are introduced as examples. While this Perspective describes living matter from a physical perspective, highlighting experimental and theoretical physics techniques relevant for such systems, it is also meant to serve as a solid starting point for researchers in the life sciences interested in the implementation of biophysical methods.

Molecular biology is messy and complex. The future of life sciences research, drug development, and many fields depends on our ability to unravel the complex, biophysical phenomena that underlie cellular function with a finer level of resolution. Using current technologies, it is challenging to conduct quantitative measurements that can reveal the complexity of life at the molecular scale. This article reviews the invention, development, and research applications of convex lens-induced confinement (CLiC) microscopy, which is a method to image molecular interactions one molecule at a time, while emulating “cell-like” conditions, with precision and control. By mechanically confining molecules to the field of view, CLiC can eliminate the complexity and potential biases inherent to “tethering” molecules. Looking forward, CLiC is being applied to emerging areas of exploration where single-molecule resolution can be transformative, including visualizing nanoparticle and protein dynamics, CRISPR-Cas9 targeting dynamics, and therapeutics applications.

Historically, research in entrepreneurship has largely ignored biological factors. However, recently researchers have begun to explore the ways in which human biology affects this phenomenon. This literature has been fragmented, scattered across various outlets, making it difficult for entrepreneurship scholars to aggregate the findings and develop a broad theoretical perspective to describe how biology relates to entrepreneurship (Nofal, Nicolaou, Symeonidou, & Shane, 2018).\ud \ud In this chapter, we provide a systematic review of the biological perspective in entrepreneurship. Specifically, we systematically review research linking the three biological strands of genetics, physiology, and neuroscience to entrepreneurship. We discuss the findings of this growing literature and how incorporating biology into the study of entrepreneurship can enhance our understanding of various entrepreneurial outcomes. We then discuss the mechanisms through which biology affects entrepreneurship. Finally, we conclude with directions for future research.\ud

DNA unwinding is an important cellular process involved in DNA replication, transcription and repair. In cells, molecular crowding caused by the presence of organelles, proteins, and other molecules affects numerous internal cellular structures. Here, we visualize plasmid DNA unwinding and binding dynamics to an oligonucleotide probe as functions of ionic strength, crowding agent concentration, and crowding agent species using single-molecule CLiC microscopy. We demonstrate increased probe–plasmid interaction over time with increasing concentration of 8 kDa polyethylene glycol (PEG), a crowding agent. We show decreased probe–plasmid interactions as ionic strength is increased without crowding. However, when crowding is introduced via 10% 8 kDa PEG, interactions between plasmids and oligos are enhanced. This is beyond what is expected for normal in vitro conditions, and may be a critically important, but as of yet unknown, factor in DNA’s proper biological function in vivo. Our results show that crowding has a strong effect on the initial concentration of unwound plasmids. In the dilute conditions used in these experiments, crowding does not impact probe–plasmid interactions once the site is unwound.

The sociological study of risk-taking behavior is a relatively recent development. Lyng (1990) and others have developed the field of edgework, or the “sociology of risk-taking.” In this study, we examine a group of edgeworkers to understand the role of fun and identity in a group of BMX “freestyle” bicycle riders and conclude that these riders reject rational reasons, in the sense of the term envisioned by Weber, for riding in favor of choosing an activity that they report as fun, which leads to feelings such as self-actualization and fulfillment. Additionally, they are not concerned that others, outside of the subculture, recognize their status as participants, further suggesting that rationality played little into the calculation used to define success by this group.

The loop invariants of Dimofte–Garoufalidis is a formal power series with arithmetically interesting coefficients that conjecturally appears in the asymptotics of the Kashaev invariant of a knot to all orders in 1/N. We develop methods implemented in SnapPy that compute the first six coefficients of the formal power series of a knot. We give examples that illustrate our method and its results.

We directly visualize the topology-mediated interactions between an unwinding site on a supercoiled DNA plasmid and a specific probe molecule designed to bind to this site, as a function of DNA supercoiling and temperature. The visualization relies on containing the DNA molecules within an enclosed array of glass nanopits using the Convex Lens-induced Confinement (CLiC) imaging method. This method traps molecules within the focal plane while excluding signal from out-of-focus probes. Simultaneously, the molecules can freely diffuse within the nanopits, allowing for accurate measurements of exchange rates, unlike other methods which could introduce an artifactual bias in measurements of binding kinetics. We demonstrate that the plasmid’s structure influences the binding of the fluorescent probes to the unwinding site through the presence, or lack, of other secondary structures. With this method, we observe an increase in the binding rate of the fluorescent probe to the unwinding site with increasing temperature and negative supercoiling. This increase in binding is consistent with the results of our numerical simulations of the probability of site-unwinding. The temperature dependence of the binding rate has allowed us to distinguish the effects of competing higher order DNA structures, such as Z-DNA, in modulating local site-unwinding, and therefore binding.

We review the empirical literature on the effects of individual income tax policy on entrepreneurship. We find no evidence of consensus, even on relatively narrow questions such as whether individual income tax rates deter or encourage entrepreneurial entry. We believe the absence of consensus reflects both the complexity of mechanisms connecting tax policy to entrepreneurial decision making and the infeasibility of employing the most reliable empirical methods, such as experiments, in this domain.

The start-ups with the most potential to innovate and generate employment are the ones most likely to rely on capital provided by outside investors. Several institutional developments including the rise of business accelerators, angel groups, and startup competitions, have meant that founders seeking this type of capital increasingly pitch their business ideas to investors in group settings, raising the question of whether the order in which ideas are pitched affects outcomes. Research on order effects in other competitive environments indicates that judges often have high expectations and calibrate their evaluations to the lower average performance of competitors at the beginning of competition, making it difficult for those going early to do as well as those performing later. We test empirically whether this calibration effect is also present for efforts by founders to pitch investors by conducting a field experiment. Entrepreneurs participating in elevator pitch competitions were randomly assigned the position in which they pitched. We find evidence of this calibration effect: investor-judges expressed substantially lesser interest in pursuing investment in the first and second ventures pitched to them.

We complete the classification of binary patterns in partial words that was started in earlier publications by proving that the partial word avoidability index of the binary pattern ABABA is two and the one of the binary pattern ABBA is three.

Behavioral genetics techniques were applied to a sample of self-employed monozygotic (MZ) and dizygotic (DZ) twins from the USA to examine whether genetic factors influence entrepreneurial performance. The study found that genetics affects the amount of income earned by self-employed people. In addition, the study found that common genes influenced the phenotypic correlations between three of the ‘big five’ personality characteristics – agreeableness, openness to experience and extraversion – and self-employment income, but due to the small sample size, the confidence intervals were high. The implications of a genetic component to self-employment income for research on entrepreneurship are discussed.

According to a study featured in the Federal Reserve Bank of Cleveland's 2005 Annual Report, differences in state income levels can be explained largely by two factors: innovation and workforce skills. The study's findings suggest that increasing a region's knowledge base should be a primary component of economic development strategies.

Sensitive visualization and conformational control of long, delicate biopolymers present critical challenges to emerging biotechnologies and biophysical studies. Next-generation nanofluidic manipulation platforms strive to maintain the structural integrity of genomic DNA prior to analysis but can face challenges in device clogging, molecular breakage, and single-label detection. We address these challenges by integrating the Convex Lens-induced Confinement (CLiC) technique with a suite of nanotopographies embedded within thin-glass nanofluidic chambers. We gently load DNA polymers into open-face nanogrooves in linear, concentric circular, and ring array formats and perform imaging with single-fluorophore sensitivity. We use ring-shaped nanogrooves to access and visualize confinement-enhanced self-ligation of long DNA polymers. We use concentric circular nanogrooves to enable hour-long observations of polymers at constant confinement in a geometry which eliminates the confinement gradient which causes drift and can alter molecular conformations and interactions. Taken together, this work opens doors to myriad biophysical studies and biotechnologies which operate on the nanoscale.

We study pattern avoidance in the context of partial words. The problem of classifying the avoidable unary patterns has been solved, so we move on to binary, ternary, and more general patterns. Our results, which are based on morphisms (iterated or not), determine all the ternary patterns’ avoidability indices or at least give bounds for them.

The tendency to be an entrepreneur may be influenced by genetic variation. Sensation seeking is more common among entrepreneurs than among the general population. Twin studies show that the tendency to be an entrepreneur is heritable and that common genes influence both sensation seeking and entrepreneurial tendency (Nicolaou et al. Manag Sci 54:167-179, Strateg Entrep J 2:7-21, ). Since dopamine receptor genes have been associated with novelty seeking/sensation seeking (Benjamin et al. Nat Genet 12:81-84, Ebstein et al. Nat Genet 12:78-80, Noblett and Coccaro Curr Psychiatry Rep 7:73-80, ), and attention deficit hyperactivity disorder (ADHD) has been reported to occur at greater rates among entrepreneurs, we examined the association between five dopamine receptor genes and four ADHD-associated genes, with the tendency to be an entrepreneur in a sample of 1,335 individuals from the UK. We found a single nucleotide polymorphism (rs1486011) of the DRD3 gene on chromosome 3 to be significantly associated with the tendency to be an entrepreneur. This result is the first evidence of the association of a specific gene with entrepreneurship. Further studies are needed to replicate this association. ABSTRACT FROM AUTHOR] Copyright of Small Business Economics is the property of Springer Science & Business Media B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) 36 2 151 155

We applied quantitative genetics techniques to a sample of 347 pairs of monozygotic and 303 pairs of dizygotic twins taken from the MIDUS database to examine the influence of genetic factors on the variation across people in the tendency to be self-employed and to choose other occupations. We found that a heritability hypothesis is supported for the tendency to be self-employed, both currently and ten years prior, with no influence of the shared environment. We also found that this heritability is substantive for male as well as female twins. Moreover, we found support for a heritability hypothesis for the intention to be self-employed in the future and for a bivariate heritability model between entrepreneurial intentions and the tendency to be self-employed. Finally, we found support for a heritability hypothesis for other occupational choices, specifically the choice to be a teacher, manager or salesperson.

We applied multivariate genetics techniques to a sample of 3,412 monozygotic and dizygotic twins from the United Kingdom and 1,300 monozygotic and dizygotic twins from the United States to examine whether genetic factors account for part of the covariance between the Big Five personality characteristics and the tendency to be an entrepreneur. We found that common genes influenced the phenotypic correlations between only Extraversion and Openness to Experience and the tendency to be an entrepreneur. Although the phenotypic correlations between the personality characteristics and the tendency to be an entrepreneur were small in size, genetic factors accounted for most of them.

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This study examined the influence of genetic factors on the tendency to engage in entrepreneurship. We found that, in the particular sample we examined, between 37 and 42 percent of the variance in the tendency of people to engage in entrepreneurship is accounted for by genetic factors. A substantial part of this variance was mediated by the psychological trait of sensation seeking, suggesting that genes affect the tendency of people to engage in entrepreneurship by affecting the distribution of sensation seeking across people.

We present the design and construction of a versatile, open frame inverted microscope system for wide-field fluorescence and single molecule imaging. The microscope chassis and modular design allow for customization, expansion, and experimental flexibility. We present two components which are included with the microscope which extend its basic capabilities and together create a powerful microscopy system: A Convex Lens-induced Confinement device provides the system with single-molecule imaging capabilities, and a two-color imaging system provides the option of imaging multiple molecular species simultaneously. The flexibility of the open-framed chassis combined with accessible single-molecule, multi-species imaging technology supports a wide range of new measurements in the health, nanotechnology, and materials science research sectors.

This paper, using a study based on a survey of 678 managers in 8 Japanese firms, examines the similarities and differences in the preferred styles of innovation championing that exist across large established Japanese companies. The results of the study show that championing styles vary greatly across Japanese organizations. The implication of this finding is that research on Japanese firms should avoid looking only for similarities which reinforce stereotypes of a "Japanese way" of managing the innovation process.

This study examines differences in corporate culture between Japanese firms as expressed in championing behaviors. The results of a survey of 678 managers in 8 Japanese firms concerning their preferences regarding innovation championing styles are reported. These show that the emphasis in previous research on the similarities between Japanese firms should be abandoned. In addition, the present study lends important support to the assumption of independence of organizational culture from social environment.

The time delay between the pump and probe pulses in attosecond time-resolved experiments, such as attosecond streaking, is commonly introduced by splitting and recombining the two pulses in an interferometer. This technique suffers from instability in the optical path lengths of the two arms due to mechanical vibration of the optical elements and fluctuating environmental conditions. We present a technique with which the instability of the unconventional interferometer is suppressed while at the same time the time delay is controlled to within 20 as RMS using a feedback loop. Using this scheme, the streaked spectrogram of an attosecond pulse was measured.

The knowledge intensive areas of our economy are characterized by rapid innovation fueled by technological and scientific advances. For firms competing in knowledgebased industries, continuous access to new information, know-how, and ideas is essential to success (Bierly and Chakrabarti, 1996). Firms create new knowledge through investments in R&D but, given the rapid pace of knowledge development around the world and the numerous scientific and technological frontiers along which innovation takes place, no firm can internally develop all the knowledge needed for success. Firms must, therefore, continuously access knowledge from other organizations including domestic and international firms, government laboratories, and universities (Arora and Gambardella, 1990; Powell et ai., 1996). One of the approaches taken by firms to monitor external knowledge development, and to absorb this knowledge when useful, is to engage in strategic alliances. Strategic alliances are used in numerous industries to gain access to ideas, knowhow, and expertise from other organizations (Inkpen, 1998). Empirical research has confirmed that alliances are an important source of scientific and technological knowledge (Mowery et at., 1996; Powell et at., 1996; Ah~ja, 2000) and contribute to firm success (Stuart, 2000).