| 1. |
- Farman, Helen H., 1983, et al.
(author)
-
Female Mice Lacking Estrogen Receptor-alpha in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass
- 2016
-
In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 157:8, s. 3242-3252
-
Journal article (peer-reviewed)abstract
- Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor(ER)alpha. Central ER alpha exerts an inhibitory role on bone mass. ER alpha is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ER alpha in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ER alpha expression specifically in POMC neurons (POMC-ER alpha(-/-)). Female POMC-ER alpha(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 mu g/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ER alpha(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+ 126 +/- 34%, P < .01) and mechanical strength (+ 193 +/- 38%, P <.01). To test whether ER alpha in VMN is involved in the regulation of bone mass, ER alpha was silenced using an adeno-associated viral vector. Silencing of ER alpha in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ER alpha in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ER alpha activity in hypothalamic POMC neuronsin ARC and stimulatory peripheral ER alpha-mediated effects in bone determines cortical bone mass in female mice.
|
|
| 2. |
- Isaksson, Olov H. D., 1980-, et al.
(author)
-
Knowledge spillovers in the supply chain : evidence from the high tech sectors
- 2016
-
In: Research Policy. - : Elsevier BV. - 0048-7333 .- 1873-7625. ; 45:3, s. 699-706
-
Journal article (peer-reviewed)abstract
- In addition to internal R&D, external knowledge is widely considered as an essential lever for innovative performance. This paper analyzes knowledge spillovers in supply chain networks. Specifically, we investigate how supplier innovation is impacted by buyer innovation. Financial accounting data is combined with supply chain relationship data and patent data for U.S. firms in high tech industries. Our econometric analysis shows that buyer innovation has a positive and significant impact on supplier innovation. We find that the duration of the buyer-supplier relationship positively moderates this effect, but that the technological proximity between the two firms does not have a significant effect on spillovers.
|
|
| 3. |
- Moser, Philipp, et al.
(author)
-
Inventory dynamics in process industries : An empirical investigation
- 2017
-
In: International Journal of Production Economics. - : Elsevier BV. - 0925-5273 .- 1873-7579. ; 191, s. 253-266
-
Journal article (peer-reviewed)abstract
- Process industry firms have thrived in recent decades, but changes in the markets are currently putting both growth and profitability at risk. In this context, inventory management is increasingly viewed as an essential lever for creating a sustainable competitive advantage. Despite this, many firms struggle to implement best practices because of industry-specific constraints. This research explores how seven fundamental characteristics of process industries drive inventory performance. We empirically investigate four process industries and four peer industries, using financial accounting, credit rating, stock market and trading data and implement a seemingly unrelated regression (SUR) equations model. Our results show that capital intensity, capital costs, transportation costs, delivery time, price volatility, demand uncertainty and gross margin directly affect a company's degree of freedom in terms of inventory management and illustrate that inventory management in process industries follows different dynamics. This study enhances the understanding of inventory drivers and gives practitioners a tool to guide future improvement efforts.
|
|
| 4. |
- Page, Brent D. G., et al.
(author)
-
Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells
- 2018
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
-
Journal article (peer-reviewed)abstract
- With a diverse network of substrates, NUDIX hydrolases have emerged as a key family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been implicated in ADPribose and 8-oxo-guanine metabolism and was recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells. Here, we further elucidate the physiological relevance of known NUDT5 substrates and underscore the biological requirement for NUDT5 in gene regulation and proliferation of breast cancer cells. We confirm the involvement of NUDT5 in ADP-ribose metabolism and dissociate a relationship to oxidized nucleotide sanitation. Furthermore, we identify potent NUDT5 inhibitors, which are optimized to promote maximal NUDT5 cellular target engagement by CETSA. Lead compound, TH5427, blocks progestin-dependent, PAR-derived nuclear ATP synthesis and subsequent chromatin remodeling, gene regulation and proliferation in breast cancer cells. We herein present TH5427 as a promising, targeted inhibitor that can be used to further study NUDT5 activity and ADP-ribose metabolism.
|
|
| 5. |
- Seifert, Daniel, et al.
(author)
-
A test of inventory models with permissible delay in payment
- 2017
-
In: International Journal of Production Research. - : Informa UK Limited. - 0020-7543 .- 1366-588X. ; 55:4, s. 1117-1128
-
Journal article (peer-reviewed)abstract
- Contrary to the long-standing view in the finance literature that firms should maximise payment delays, research in operations management suggests that long payment delays can be suboptimal. In this study, we reconcile these two views by applying a secondary data approach to established operations management theory. Based on a sample of 3383 groups of public US firms from a novel database, we find that our data are consistent with the causal relations and theoretical predictions of the operations management literature. Firm profitability is positively associated with payment delay. Payment delay, in turn, is positively associated with the capital cost difference between buyer and supplier and negatively associated with the price elasticity of demand and the deterioration rate of inventory. However, we do not observe any significant interaction effects between these factors, which raise a number of questions for future research.
|
|
| 6. |
|
|
