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"Huber, Thomas"
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Governance Practices in Platform Ecosystems: Navigating Tensions Between Cocreated Value and Governance Costs
Based on an exploratory multiple-case study in two platform ecosystems, we develop a process theory that explains how and why different ways of practicing ecosystem-wide governance are more or less successful in navigating the tension between cocreated value and governance costs. Our process theory shows that how ecosystem-wide rules and values are practiced considerably varies and changes over time. Initially, governance practices follow ecosystem-wide rules; if and how practices shift toward going beyond the rules hinges on specific necessary conditions. Irrespective of which governance route is taken, the tension between cocreated value and governance costs is more successfully addressed if practices are sensitive to ecosystem-wide values.
The online appendix is available at
https://doi.org/10.1287/isre.2017.0701
.
Journal Article
Continuous Contracting in Software Outsourcing: Towards A Configurational Theory
Contemporary software outsourcing projects increasingly employ continuous contracting, where an umbrella agreement is followed by periodic contracts. Consequently, both contract design and project control become episodic, thereby dissolving the traditional boundary between the two and requiring managers to holistically combine them into cohesive governance configurations aimed at achieving alignment and flexibility. Despite the growing popularity of continuous contracting, we lack insights into how governance configurations are formed, evolve, and influence project outcomes. We address this gap through a longitudinal, multimethod study of 33 governance episodes across three multiyear software projects executed under a common umbrella agreement. Using thematic analysis, we first identified three dimensions (content, contingency, timing) to capture salient characteristics of both contract design and project control. Applying crisp-set qualitative comparative analysis (csQCA), we then identified eight governance configurations, consistently linked to specific alignment and flexibility outcomes. The narrative analysis revealed that these episodic outcomes depend on specific interactions among the governance elements within a configuration—namely, whether they substitute for each other (replacing interactions) or offset their limitations (compensating interactions). It furthermore showed how governance configurations evolve across successive episodes: Initially, managers primarily rely on configurations producing either alignment or flexibility. However, as trust and knowledge increase, the governance repertoire expands, enabling configurations that simultaneously achieve alignment and flexibility through compensating interactions. Managers can thus steer projects more deliberately, thereby enhancing overall project performance. We synthesized these insights into a configurational theory of continuous contracting with important implications for outsourcing governance research and actionable guidance for practitioners.
Journal Article
A Process Model of Complementarity and Substitution of Contractual and Relational Governance in IS Outsourcing
This paper develops a process model of how and why complementarity and substitution form over time between contractual and relational governance in the context of information systems outsourcing. Our analysis identifies four distinct process patterns that explain this formation as the outcome of interaction processes between key elements of both contractual and relational governance. These patterns unveil the dynamic nature of complementarity and substitution. In particular, we show that the relationship between contractual and relational governance oscillates between complementarity and substitution. Those oscillations are triggered mainly by three types of contextual events (goal fuzziness, goal conflict, and goal misalignment). Surprisingly, substitution of informal control did not occur as an immediate reaction to external events but emerged as a consequence of preceding complementarity. Thus, our study challenges the prevailing view of an either/or dichotomy of complementarity and substitution by showing that they are causally connected over time.
Journal Article
Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma
Yu Chen and colleagues describe a new constitutively activating mutation in the G-protein-coupled receptor
CYSLTR2
in patients with uveal melanoma lacking mutations in the G-protein-encoding genes
GNAQ
and
GNA11
. They find that expression of the mutant leads to increased expression of melanocyte-lineage signature genes and promotes tumorigenesis
in vivo
.
Uveal melanomas are molecularly distinct from cutaneous melanomas and lack mutations in
BRAF
,
NRAS
,
KIT
, and
NF1
. Instead, they are characterized by activating mutations in
GNAQ
and
GNA11
, two highly homologous α subunits of G
αq/11
heterotrimeric G proteins, and in
PLCB4
(phospholipase C β4), the downstream effector of G
αq
signaling
1
,
2
,
3
. We analyzed genomics data from 136 uveal melanoma samples and found a recurrent mutation in
CYSLTR2
(cysteinyl leukotriene receptor 2) encoding a p.Leu129Gln substitution in 4 of 9 samples that lacked mutations in
GNAQ
,
GNA11
, and
PLCB4
but in 0 of 127 samples that harbored mutations in these genes. The Leu129Gln CysLT
2
R mutant protein constitutively activates endogenous G
αq
and is unresponsive to stimulation by leukotriene. Expression of Leu129Gln CysLT
2
R in melanocytes enforces expression of a melanocyte-lineage signature, drives phorbol ester–independent growth
in vitro
, and promotes tumorigenesis
in vivo
. Our findings implicate
CYSLTR2
as a uveal melanoma oncogene and highlight the critical role of G
αq
signaling in uveal melanoma pathogenesis.
Journal Article
Gender Differences in Treatment Outcomes for Eating Disorders: A Case-Matched, Retrospective Pre–Post Comparison
Eating disorders (EDs) are increasingly emerging as a health risk in men, yet men remain underrepresented in ED research, including interventional trials. This underrepresentation of men may have facilitated the development of women-centered ED treatments that result in suboptimal outcomes for men. The present study retrospectively compared pre- vs. post-treatment outcomes between age-, diagnosis-, and length-of-treatment-matched samples of n = 200 men and n = 200 women with Anorexia Nervosa (AN), Bulimia Nervosa (BN), Binge Eating Disorder (BED), or Eating Disorder Not Otherwise Specified (EDNOS), treated in the same setting during the same period, and using the same measurements. Compared to women, men with AN showed marked improvements in weight gains during treatment as well as in ED-specific cognitions and general psychopathology. Likewise, men with BED showed marked weight loss during treatment compared to women with BED; ED-specific cognitions and general psychopathology outcomes were comparable in this case. For BN and EDNOS, weight, ED-specific cognitions, and general psychopathology outcomes remained largely comparable between men and women. Implications for treatments are discussed.
Journal Article
The State Urge to be Physically Active‐Questionnaire (SUPA‐Q): Development and validation of a state measure of activity urges in patients with eating disorders
Many people, including patients with eating disorders (EDs), experience an increased urge for physical activity. \"Trait\"-like activity in patients with EDs is assessed by existing questionnaires, but there are few clinically validated assessments of a \"state\" urge to be physically active. Here, we developed and validated the State Urge to be Physically Active-Questionnaire (SUPA-Q).
After developing and piloting the items, N = 126 patients with EDs (mostly anorexia nervosa and bulimia nervosa) took part in our mixed-longitudinal validation study with one primary assessment for all patients and a secondary assessment for a subsample of patients. Cronbach's α and split-half-methods served as measures of consistency and reliability. Correlations with other questionnaires were used to determine convergent and divergent validity, and confirmatory factor analysis was used for investigating factorial validity. We used paired-samples t-tests for repeated assessments to investigate change sensitivity.
We found the SUPA-Q to be highly consistent, and reliable and to demonstrate convergent, divergent, and factorial validity. The comparison of SUPA-Q scores from repeated assessments within a subsample of patients demonstrated the questionnaire's change sensitivity, Cohen's d = 0.48. Moreover, an increase in SUPA-Q scores was associated with a less positive mood, more anxiety, more body dissatisfaction, more tenseness, less feelings of control, and more stress.
The newly developed SUPA-Q may help to accentuate the necessity to evaluate and address the acute urge to engage in physical activity in patients with EDs in clinical practice and ultimately support tailoring treatments to patients' unique symptom patterns. The questionnaire is available at https://doi.org/10.17605/OSF.IO/G2YBC.
Journal Article
FTIR analysis of GPCR activation using azido probes
We demonstrate the site-directed incorporation of an IR-active amino acid,
p
-azido-
L
-phenylalanine (azidoF,
1
), into the G protein–coupled receptor rhodopsin using amber codon suppression technology. The antisymmetric stretch vibration of the azido group absorbs at ∼2,100 cm
−1
in a clear spectral window and is sensitive to its electrostatic environment. We used FTIR difference spectroscopy to monitor the azido probe and show that the electrostatic environments of specific interhelical networks change during receptor activation.
Journal Article
Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels
Significance Targeting WNT (Wingless-type)/β-catenin signaling has emerged as an attractive novel therapeutic approach to the treatment of bone diseases. We previously identified LRP4 (low-density lipoprotein receptor-related protein 4) as a facilitator of action of the WNT signaling antagonist SOST/sclerostin in vitro. Here, we generated bone-specific Lrp4 -deficient mouse lines and anti-LRP4 antibodies selectively disrupting the Lrp4 sclerostin facilitator function. Using these novel genetic and pharmacological tools, we demonstrate that disruption of Lrp4 function induces bone gain in vivo and results in highly elevated circulating sclerostin levels. Together, these findings provide important novel insights into the role of LRP4 as a key regulator of bone homeostasis and into the mode of action of sclerostin and provide a new strategy for promoting bone gain through targeting of the WNT pathway.
We identified previously in vitro LRP4 (low-density lipoprotein receptor-related protein 4) as a facilitator of the WNT (Wingless-type) antagonist sclerostin and found mutations disrupting this function to be associated with high bone mass in humans similar to patients lacking sclerostin. To further delineate the role of LRP4 in bone in vivo, we generated mice lacking Lrp4 in osteoblasts/osteocytes or osteocytes only. Lrp4 deficiency promoted progressive cancellous and cortical bone gain in both mutants, although more pronouncedly in mice deficient in osteoblast/osteocyte Lrp4 , consistent with our observation in human bone that LRP4 is most strongly expressed by osteoblasts and early osteocytes. Bone gain was related primarily to increased bone formation. Interestingly, Lrp4 deficiency in bone dramatically elevated serum sclerostin levels whereas bone expression of Sost encoding for sclerostin was unaltered, indicating that osteoblastic Lrp4 retains sclerostin within bone. Moreover, we generated anti-LRP4 antibodies selectively blocking sclerostin facilitator function while leaving unperturbed LRP4–agrin interaction, which is essential for neuromuscular junction function. These antibodies increased bone formation and thus cancellous and cortical bone mass in skeletally mature rodents. Together, we demonstrate a pivotal role of LRP4 in bone homeostasis by retaining and facilitating sclerostin action locally and provide a novel avenue to bone anabolic therapy by antagonizing LRP4 sclerostin facilitator function.
Journal Article