On the edge of destruction: An impaired-regulation model of destructive entrepreneurial action

Entrepreneurial action can be directed toward identifying, generating, and exploiting potential business opportunities that can cause harm to others. Over and above the “rules of the game” of the economic system, we theorize on destructive entrepreneurial actions that result from entrepreneurs’ impaired regulation of their decision making. Specifically, we build on the entrepreneurial action literature and draw on regulation theories of goal attainment and moral disengagement to develop an impaired-regulation model of destructive entrepreneurial actions. This model contributes to the entrepreneurship literature by providing new insights into (1) why some entrepreneurs are more susceptible to engaging their ventures in destructive entrepreneurial actions, (2) everyday entrepreneurs (the “who”) engaging in destructive entrepreneurial actions (i.e., the “how” and “why”), and (3) when and why some entrepreneurs respond to their destructive entrepreneurial actions by becoming repentant do-gooders while others grow into serial offenders

Pandemic Makers: How Citizen Groups Mobilized Resources to Meet Local Needs in a Global Health Crisis

The enormous scale of suffering, breadth of societal impact, and ongoing uncertainty wrought by the COVID-19 pandemic introduced dynamics seldom examined in the crisis entrepreneurship literature. Previous research indicates that when a crisis causes a failure of public goods, spontaneous citizen ventures often emerge to leverage unique local knowledge to rapidly customize abundant external resources to meet immediate needs. However, as outsiders, emergent citizen groups responding to the dire shortage of personal protective equipment at the onset of COVID-19 lacked local knowledge and legitimacy. In this study, we examine how entrepreneurial citizens mobilized collective resources in attempts to gain acceptance and meet local needs amid the urgency of the pandemic. Through longitudinal case studies of citizen groups connected to makerspaces in four U.S. cities, we study how they adapted to address the resource and legitimacy limitations they encountered. We identify three mechanisms?augmenting, circumventing, and attenuating?that helped transient citizen groups calibrate their resource mobilization based on what they learned over time. We highlight how extreme temporality imposes limits on resourcefulness and legitimation, making it critical for collective entrepreneurs to learn when to work within their limitations rather than try to overcome them

Enzymatic Characterization of ER Stress-Dependent Kinase, PERK, and Development of a High-Throughput Assay for Identification of PERK Inhibitors

PERK is serine/threonine kinase localized to the endoplasmic reticulum (ER) membrane. PERK is activated and contributes to cell survival in response to a variety of physiological stresses that affect protein quality control in the ER, such as hypoxia, glucose depravation, increased lipid biosynthesis, and increased protein translation. Pro-survival functions of PERK are triggered by such stresses, suggesting that development of small-molecule inhibitors of PERK may be efficacious in a variety of disease scenarios. Hence, we have conducted a detailed enzymatic characterization of the PERK kinase to develop a high-throughput-screening assay (HTS) that will permit the identification of small-molecule PERK inhibitors. In addition to establishing the Km of PERK for both its primary substrate, eIF2?, and for adenosine triphosphate, further mechanistic studies revealed that PERK targets its substrate via either a random/steady-state ordered mechanism. For HTS, we developed a time-resolved fluorescence resonance energy transfer–based assay that yielded a robust Z? factor and percent coefficient of variation value, enabling the successful screening of 79,552 compounds. This approach yielded one compound that exhibited good in vitro and cellular activity. These results demonstrate the validity of this screen and represent starting points for drug discovery efforts

An anti-large T-antigen strategy to develop anti-JCV drugs

There are currently no JCV-specific therapies available for clinical use. This study evaluates viral large T antigen (LTA) as a potential target for drug development. LTA is a hexameric protein with a helicase activity that is powered by ATP binding and hydrolysis. The helicase and ATPase function is critical for viral replication and inhibition by small molecules would disrupt the viral life cycle. LTA is a valid target for discovery of anti-JCV drugs. The hits identified are reasonable starting points for medicinal chemistry to improve potency and selectivity. Screening of additional chemical libraries could also be considered to identify chemical structures that may be more potent with acceptable cytotoxicity

“Early Rupture of Membranes” during Induced Labor as a Risk Factor for Cesarean Delivery in Term Nulliparas

OBJECTIVE: To determine if "early rupture of membranes" (early ROM) during induction of labor is associated with an increased risk of cesarean section in term nulliparas. STUDY DESIGN: The rate of cesarean section and the timing of ROM during the course of labor were examined in term singleton nulliparas whose labor was induced. Cases were divided into 2 groups according the timing of ROM: 1)"early ROM", defined as ROM at a cervical dilatation<4 cm during labor; and 2) "late ROM", ROM at a cervical dilatation≥4 cm during labor. Nonparametric techniques were used for statistical analysis. RESULTS: 1) In a total of 500 cases of study population, "early ROM" occurred in 43% and the overall cesarean section rate was 15.8%; 2) patients with "early ROM" had a higher rate of cesarean section and cesarean section due to failure to progress than did those with "late ROM" (overall cesarean section rate: 24%[51/215] vs. 10%[28/285], p<0.01; cesarean section rate due to failure to progress: 18%[38/215] vs. 8%[22/285], p<0.01 for each) and this difference remained significant after adjusting for confounding variables. CONCLUSION: "Early ROM" during the course of induced labor is a risk factor for cesarean section in term singleton nulliparas

Risk of caesarean section after induced labour: do hospitals make a difference

Background: There is a well-known relationship between induced labour and caesarean rates. However, it remains unknown whether this relationship reflects the impact of more complex obstetric conditions or the variability in obstetric practices. We sought to quantify the independent role of the hospital as a variable that can influence the occurrence of caesarean section after induced labour. Methods: As part of the Portuguese Generation XXI birth cohort, we evaluated 2041 consecutive women who underwent singleton pregnancies with labour induction, at five public level III obstetric units (April 2005-August 2006). The indications for induction were classified according to the guidelines of the American and the Royal Colleges of Obstetricians and Gynaecologists. Poisson regression models were adjusted to estimate the association between the hospital and surgical delivery after induction. Crude and adjusted prevalence ratios (PR) and a 95% confidence interval (95% CI) were computed. Results: The proportion of women who were induced without formal clinical indications varied among hospitals from 20.3% to 45.5% (p < 0.001). After adjusting for confounders, the risk of undergoing a caesarean section after induced labour remained significantly different between the hospitals, for the cases in which there was no evident indication for induction [the highest PR reaching 1.86 (95% CI, 1.23–2.82)] and also when at least one such indication was present [1.53 (95% CI, 1.12–2.10)]. This pattern was also observed among the primiparous cephalic term induced women [the highest PR reaching 2.06 (95% CI, 1.23–2.82) when there was no evident indication for induction and 1.61 (95% CI, 1.11–2.34) when at least one such indication was present]. Conclusions:Caesarean section after induced labour varied significantly across hospitals where similar outcomes were expected. The effect was more evident when the induction was not based on the unequivocal presence of commonly accepted indications