Constructing entrepreneurial identities: the case of entrepreneurial dyads

This thesis investigates the processes of identity construction and identity work in entrepreneurial dyads. Entrepreneurial dyads are defined as two-person teams, in which members are bound both by a strong social tie and by a common commitment to start and manage a new business venture. The thesis builds on the work of Watson (2008) and adopts his conceptual framework for understanding how discourse shapes social identities and how these are used to inform the production of a coherent self. The business stories of three entrepreneurial dyads are used as case studies. Data were collected through both storytelling in interviews and direct observation. Entrepreneurs were asked to produce an individual account of their business story. In addition, the dyads' interactive dynamics were directly observed in their natural settings. The business stories produced by the dyads were analysed using the narrative method. First, the narrative styles of the business stories were assessed looking at elements such as plot, structure, and characterisation. This analysis allowed an understanding of the socially available discourses which provided the entrepreneurs with a system of meanings that shaped their presentations. Second, a process of narrative deconstruction allowed the identification of their locally meaningful discourse, uniquely created within each dyad by social interaction. What emerged shows that the entrepreneurs recounted not only traditional business stories, but enacted a unique discourse of 'being entrepreneurial'

Small beer? Peer-to-peer lending in the craft beer sector

Peer to peer lending has advantages of ease of access to finance, timely and efficient delivery of funding, and is particularly beneficial at a specific time in the life cycle of the firm

Conformational transitions of the sodium-dependent sugar transporter, vSGLT.

Sodium-dependent transporters couple the flow of Na+ ions down their electrochemical potential gradient to the uphill transport of various ligands. Many of these transporters share a common core structure composed of a five-helix inverted repeat and deliver their cargo utilizing an alternating-access mechanism. A detailed characterization of inward-facing conformations of the Na+-dependent sugar transporter from Vibrio parahaemolyticus (vSGLT) has previously been reported, but structural details on additional conformations and on how Na+ and ligand influence the equilibrium between other states remains unknown. Here, double electron-electron resonance spectroscopy, structural modeling, and molecular dynamics are utilized to deduce ligand-dependent equilibria shifts of vSGLT in micelles. In the absence and presence of saturating amounts of Na+, vSGLT favors an inward-facing conformation. Upon binding both Na+ and sugar, the equilibrium shifts toward either an outward-facing or occluded conformation. While Na+ alone does not stabilize the outward-facing state, gating charge calculations together with a kinetic model of transport suggest that the resting negative membrane potential of the cell, absent in detergent-solubilized samples, may stabilize vSGLT in an outward-open conformation where it is poised for binding external sugars. In total, these findings provide insights into ligand-induced conformational selection and delineate the transport cycle of vSGLT

Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1.

The voltage-dependent anion channel (VDAC) is the most abundant protein in the outer mitochondrial membrane and constitutes the primary pathway for the exchange of ions and metabolites between the cytosol and the mitochondria. There is accumulating evidence supporting VDAC's role in mitochondrial metabolic regulation and apoptosis, where VDAC oligomerization has been implicated with these processes. Herein, we report a specific pH-dependent dimerization of murine VDAC1 (mVDAC1) identified by double electron-electron resonance and native mass spectrometry. Intermolecular distances on four singly spin-labeled mVDAC1 mutants were used to generate a model of the low-pH dimer, establishing the presence of residue E73 at the interface. This dimer arrangement is different from any oligomeric state previously described, and it forms as a steep function of pH with an apparent pKa of 7.4. Moreover, the monomer-dimer equilibrium affinity constant was determined using native MS, revealing a nearly eightfold enhancement in dimerization affinity at low pH. Mutation of E73 to either alanine or glutamine severely reduces oligomerization, demonstrating the role of protonated E73 in enhancing dimer formation. Based on these results, and the known importance of E73 in VDAC physiology, VDAC dimerization likely plays a significant role in mitochondrial metabolic regulation and apoptosis in response to cytosolic acidification during cellular stress

The global, regional, and national burden of colorectal cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Data about the global, regional, and country-specific variations in the levels and trends of colorectal cancer are required to understand the impact of this disease and the trends in its burden to help policy makers allocate resources. Here we provide a status report on the incidence, mortality, and disability caused by colorectal cancer in 195 countries and territories between 1990 and 2017. Methods Vital registration, sample vital registration, verbal autopsy, and cancer registry data were used to generate incidence, death, and disability-adjusted life-year (DALY) estimates of colorectal cancer at the global, regional, and national levels. We also determined the association between development levels and colorectal cancer age-standardised DALY rates, and calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. All of the estimates are reported as counts and age-standardised rates per 100000 person-years, with some estimates also presented by sex and 5-year age groups. Findings In 2017, there were 1·8 million (95% UI 1·8–1·9) incident cases of colorectal cancer globally, with an agestandardised incidence rate of 23·2 (22·7–23·7) per 100 000 person-years that increased by 9·5% (4·5–13·5) between 1990 and 2017. Globally, colorectal cancer accounted for 896 000 (876 300–915 700) deaths in 2017, with an agestandardised death rate of 11·5 (11·3–11·8) per 100 000 person-years, which decreased between 1990 and 2017 (–13·5% [–18·4 to –10·0]). Colorectal cancer was also responsible for 19·0 million (18·5–19·5) DALYs globally in 2017, with an age-standardised rate of 235·7 (229·7–242·0) DALYs per 100000 person-years, which decreased between 1990 and 2017 (–14·5% [–20·4 to –10·3]). Slovakia, the Netherlands, and New Zealand had the highest age-standardised incidence rates in 2017. Greenland, Hungary, and Slovakia had the highest age-standardised death rates in 2017. Numbers of incident cases and deaths were higher among males than females up to the ages of 80–84 years, with the highest rates observed in the oldest age group (≥95 years) for both sexes in 2017. There was a non-linear association between the Socio-demographic Index and the Healthcare Access and Quality Index and age-standardised DALY rates. In 2017, the three largest contributors to DALYs at the global level, for both sexes, were diet low in calcium (20·5% [12·9–28·9]), alcohol use (15·2% [12·1–18·3]), and diet low in milk (14·3% [5·1–24·8]). Interpretation There is substantial global variation in the burden of colorectal cancer. Although the overall colorectal cancer age-standardised death rate has been decreasing at the global level, the increasing age-standardised incidence rate in most countries poses a major public health challenge across the world. The results of this study could be useful for policy makers to carry out cost-effective interventions and to reduce exposure to modifiable risk factors, particularly in countries with high incidence or increasing burden

Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site

Many pathogenic bacteria utilise sialic acids as an energy source or use them as an external coating to evade immune detection. As such, bacteria that colonise sialylated environments deploy specific transporters to mediate import of scavenged sialic acids. Here, we report a substrate-bound 1.95 Å resolution structure and subsequent characterisation of SiaT, a sialic acid transporter from Proteus mirabilis. SiaT is a secondary active transporter of the sodium solute symporter (SSS) family, which use Na+ gradients to drive the uptake of extracellular substrates. SiaT adopts the LeuT-fold and is in an outward-open conformation in complex with the sialic acid N-acetylneuraminic acid and two Na+ ions. One Na+ binds to the conserved Na2 site, while the second Na+ binds to a new position, termed Na3, which is conserved in many SSS family members. Functional and molecular dynamics studies validate the substrate-binding site and demonstrate that both Na+ sites regulate N-acetylneuraminic acid transport

Similarity Patterns and Stability of Environmental Response in Sunflower Hybrids

The rationale for the following research was to analyse the response of sunflower hybrids to different sowing dates and to evaluate hybrid response to critical environmental conditions. The data used are from an experiment conducted in a location-year combination over a period of two years (2007-09) in southern Italy. Eleven hybrids were tested following a randomized complete block design with three replications at each location-year combination. Eight agronomic characters including seed oil content were recorded. Classification and ordination procedures were used to investigate hybrid performance in relation to three different sowing dates. Combined analysis of variance showed that hybrids, location-year combination, sowing date and their interactions were highly significant for all characters. Hybrid performances were classified by cluster analysis into groups that were differentiable in terms of means and stability. The first three components accounted for 74%, 82%, and 87% of the total variation for the first, second and third sowing date respectively. Plotting component one against component two along Euclidean axes should therefore provide a reasonable representation of the spatial arrangements of hybrid performances in the original multi-dimensional space. The applied statistical method gives full information on hybrid performances similarity

Burden of injuries in Nepal, 1990–2017: Findings from the Global Burden of Disease Study 2017

Background: Nepal is a low-income country undergoing rapid political, economic and social development. To date, there has been little evidence published on the burden of injuries during this period of transition.Methods: The Global Burden of Disease Study (GBD) is a comprehensive measurement of population health outcomes in terms of morbidity and mortality. We analysed the GBD 2017 estimates for deaths, years of life lost, years lived with disability, incidence and disability-adjusted life years (DALYs) from injuries to ascertain the burden of injuries in Nepal from 1990 to 2017.Results: There were 16 831 (95% uncertainty interval 13 323 to 20 579) deaths caused by injuries (9.21% of all-cause deaths (7.45% to 11.25%)) in 2017 while the proportion of deaths from injuries was 6.31% in 1990. Overall, the injury-specific age-standardised mortality rate declined from 88.91 (71.54 to 105.31) per 100 000 in 1990 to 70.25 (56.75 to 85.11) per 100 000 in 2017. In 2017, 4.11% (2.47% to 6.10%) of all deaths in Nepal were attributed to transport injuries, 3.54% (2.86% to 4.08%) were attributed to unintentional injuries and 1.55% (1.16% to 1.85%) were attributed to self-harm and interpersonal violence. From 1990 to 2017, road injuries, falls and self-harm all rose in rank for all causes of death.Conclusions: The increase in injury-related deaths and DALYs in Nepal between 1990 and 2017 indicates the need for further research and prevention interventions. Injuries remain an important public health burden in Nepal with the magnitude and trend of burden varying over time by cause-specific, sex and age group. Findings from this study may be used by the federal, provincial and local governments in Nepal to prioritise injury prevention as a public health agenda and as evidence for country-specific interventions