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New digital technologies have promoted the changes in all walks of life, and the digital tide has affected the transformation, upgrading and development of enterprises. This paper takes Haidilao as an example to discuss the process and realization of the digital transfer of Haidilao, analyzes the opportunities and trends of Haidilao, and puts forward some suggestions. The results and conclusions of this paper are helpful to improve the development quality of Haidilao and so on.

Experimental studies suggest that the fracture toughness of rocks increases with the confining pressure. Among many methods to quantify this dependency, a so-called burst experiment (Abou-Sayed, 1978) may be the most widely applied in practice. Its thick wall cylinder geometry leads to a stress state resembling the subsurface condition of a pressurized wellbore with bi-wing fractures. The fracture toughness of a sample, under a given confinement pressure, can be recovered from the critical pressure upon which the bi-wing cracks propagate. Traditionally, this critical pressure is thought to correspond to a sudden drop in injection pressure. However, as the standard configuration was deliberately designed to obtain stable fracture growth at the onset, propagation can take place well before this drop in pressure, and one may overestimate the fracture toughness from measured pressures. Here, we study crack stability in the burst experiment and propose modifications to the experimental design which promotes unstable fracture growth and makes the critical pressure less ambiguous to interpret. We found that experiments with the original, stable design can lead to inconsistent measurement of fracture toughness under confining pressure, while results from unstable configurations are more consistent. Our claim on the stability was also supported by the recorded acoustic emissions from both stable and unstable experiments.

Background Thoracic aortic aneurysms (TAA) are a progressive disease characterized by inflammation, smooth muscle cell activation and matrix degradation. We hypothesized that mesenchymal stem cells (MSCs) can immunomodulate vascular inflammation and remodeling via altered microRNA (miRNAs) expression profile to attenuate TAA formation. Materials and methods C57BL/6 mice underwent topical elastase application to form descending TAAs. Mice were also treated with MSCs on days 1 and 5 and aortas were analyzed on day 14 for aortic diameter. Cytokine array was performed in aortic tissue and total RNA was tagged and hybridized for miRNAs microarray analysis. Immunohistochemistry was performed for elastin degradation and leukocyte infiltration. Results Treatment with MSCs significantly attenuated aortic diameter and TAA formation compared to untreated mice. MSC administration also attenuated T-cell, neutrophil and macrophage infiltration and prevented elastic degradation to mitigate vascular remodeling. MSC treatment also attenuated aortic inflammation by decreasing proinflammatory cytokines (CXCL13, IL-27, CXCL12 and RANTES) and upregulating anti-inflammatory interleukin-10 expression in aortic tissue of elastase-treated mice. TAA formation demonstrated activation of specific miRNAs that are associated with aortic inflammation and vascular remodeling. Our results also demonstrated that MSCs modulate a different set of miRNAs that are associated with decrease leukocyte infiltration and vascular inflammation to attenuate the aortic diameter and TAA formation. Conclusions These results indicate that MSCs immunomodulate specific miRNAs that are associated with modulating hallmarks of aortic inflammation and vascular remodeling of aortic aneurysms. Targeted therapies designed using MSCs and miRNAs have the potential to regulate the growth and development of TAAs.

Introduction: Abdominal aortic aneurysms (AAA) are characterized by vascular inflammation and remodeling that can lead to aortic rupture resulting in significant risk of mortality. Spironolactone has been recently described as a pannexin-1 (Panx1) channel modulator. Our hypothesis focuses on the role of spironolactone on Panx1 channels to attenuate AAA formation. Methods: A topical elastase (0.4 U/mL type 1 porcine pancreatic elastase) or heat inactivated elastase (control) AAA model was used in C57BL/6 (wild-type; WT) male mice. Mice were administered either a vehicle control (saline) or spironolactone (1.25 mg/kg) i.p. daily for 14 days. On day 14, the abdominal aortic diameter was measured by video micrometry and expressed as percentage increase over baseline. In a second model, mice were subjected to β-aminopropionitrile (BAPN) two days prior to elastase treatment and everyday thereafter. A vehicle control (saline) or spironolactone was given i.p. daily starting from day 14. Immunohistochemistry was used to analyze immune cell infiltration and elastic fiber disruption (Verhoeff Van Gieson staining). Groups were compared using ANOVA and data is displayed as mean ± SEM with p Results: Aortic diameter was significantly increased in elastase-treated WT mice compared to controls (202.5 ± 4.2% vs 0.5 ± 1.9%; n=9/group, p Conclusion: These results suggest spironolactone mitigates aortic remodeling to attenuate AAA formation as well as decrease growth of preformed aneurysms. Further studies aim to characterize the molecular mechanisms of specific intercellular interactions involving Panx1-mediated AAA formation by spironolactone.

Objective Hemodialysis access-related hand dysfunction is a common clinical feature of patients with chronic kidney disease (CKD) after arteriovenous fistula (AVF) placement. The heterogeneity in symptoms and the lack of a predictive association with changes in hemodynamic alterations precipitated by the AVF suggest that other factors are involved in the mechanisms responsible for causing hand and limb dysfunction postoperatively. To the best of our knowledge, no suitable animal models have provided a platform for performing preclinical experiments designed to elucidate the biologic drivers of access-related hand dysfunction. Therefore, our objective was to develop a novel murine AVF model that could be used to study dialysis access-related limb dysfunction. Methods Male 8-week-old C57BL/6J mice (n = 15/group) were exposed to either an adenine-supplemented diet to induce CKD or casein-based chow (control). Four weeks after the diet intervention, the mice were randomly assigned to receive an iliac AVF (n = 10/group) or sham surgery (n = 5/group) on the left hindlimb. The mice were sacrificed 2 weeks after surgery, and AVF specimens and hindlimb skeletal muscles were collected for further analysis. Results Before AVF or sham surgery, the glomerular filtration rates were significantly reduced and the blood urea nitrogen levels were significantly elevated in the CKD groups compared with the controls (P < .05). AVF surgery was associated with an ∼80% patency rate among the survivors (four control and three CKD mice died postoperatively). Patency was verified by changes in hemodynamics using Doppler ultrasound imaging and altered histologic morphology. Compared with sham surgery, AVF surgery reduced ipsilateral hindlimb perfusion to the tibialis anterior muscle (20%-40%) and paw (40%-50%), which remained stable until euthanasia. Analysis of gastrocnemius muscle mitochondrial respiratory function uncovered a significant decrease (40%-50%) in mitochondrial function in the AVF mice. No changes were found in the muscle mass, myofiber cross-sectional area, or centrally nucleated fiber proportion in the extensor digitorum longus and soleus muscles between the sham and AVF mice. Conclusions The results from the present study have demonstrated that iliac AVF formation is a practical animal model that facilitates examination of hemodialysis access-related limb dysfunction. AVF surgery produced the expected hemodynamic changes, and evaluation of the limb muscle revealed a substantial mitochondrial impairment that was present without changes in muscle size., Clinical Relevance Autogenous arteriovenous fistula creation remains the preferred vascular access option for patients requiring chronic hemodialysis therapy. However, access-related hand dysfunction (ARHD) remains highly prevalent in this population. Clinical management of the disability is difficult because of symptom heterogeneity and limited treatment options. Additionally, the current preclinical models do not adequately replicate the pathologic condition to allow for investigation of underlying mechanisms and to test new therapies. Therefore, medical progress has been marginal. In the present study, we have outlined a novel murine model to study ARHD and described the associated mitochondrial impairments, providing a unique tool for preclinical therapeutic development., Visual abstract

Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed continuous loop, generated through various backsplicing events of pre-mRNA. An accumulating number of studies have shown that circRNAs are potential biomarkers for major human diseases such as cancer and Alzheimer’s disease. Thus, identification and prediction of human disease-associated circRNAs are of significant importance. To this end, a computational analysis-assisted strategy is indispensable to detect, verify, and quantify circRNAs for downstream applications. In this review, we briefly introduce the biology of circRNAs, including the biogenesis, characteristics, and biological functions. In addition, we outline about 30 recent bioinformatic analysis tools that are publicly available for circRNA study. Principles for applying these computational strategies and considerations will be briefly discussed. Lastly, we give a complete survey on more than 20 key computational databases that are frequently used. To our knowledge, this is the most complete and updated summary on publicly available circRNA resources. In conclusion, this review summarizes key aspects of circRNA biology and outlines key computational strategies that will facilitate the genome-wide identification and prediction of circRNAs.

Background Male gender is a well-established risk factor for abdominal aortic aneurysm (AAA), whereas estrogen is hypothesized to play a protective role. Although rupture rates are higher in women, these reasons remain unknown. In the present study, we sought to determine if female mice are protected from AAA rupture. Materials and methods Apolipoprotein E–deficient male and female mice (aged 7 wk; n = 25 per group) were infused with angiotensin II (AngII; 2000 ng/kg/min) plus β-aminopropionitrile (BAPN) in the drinking water for 28 d to test the effects of gender on AAA rupture. Separately, a second group of male apolipoprotein E–deficient mice underwent AngII infusion + BAPN while being fed high-fat phytoestrogen free or a high-fat phytoestrogen diet to assess effects of phytoestrogens on rupture. In a third group, female mice either underwent oophorectomy or sham operation 4 wk before infusion of AngII and BAPN to further test the effects of female hormones on AA rupture. Surviving mice abdominal aorta were collected for histology, cytokine array, and gelatin zymography on postoperative day 28. Results Female mice had decreased AAA rupture rates (16% versus 46%; P = 0.029). Female mice expressed fewer elastin breaks (P = 0.0079) and decreased smooth muscle cell degradation (P = 0.0057). Multiple cytokines were also decreased in the female group. Gelatin zymography demonstrated significantly decreased pro-matrix metalloproteinase 2 in female mice (P = 0.001). Male mice fed a high dose phytoestrogen diet failed to decrease AAA rupture. Female mice undergoing oophorectomy did not have accelerated aortic rupture. Conclusions These data are the first to attempt to tease out hormonal effects on AAA rupture and the possible role of gender in rupture.

Introduction: Resolvin D1 (RvD1) is derived from a ω-3 polyunsaturated fatty acid and is involved in the resolution phase of inflammation during abdominal aortic aneurysm (AAA) formation. Hypothesis: The aim of this study was to decipher the protective role of RvD1 via formyl peptide receptor 2 (FPR2) receptor signaling in attenuating AAA formation. Methods: C57BL/6 (WT) and FPR2 -/- mice (8-12 week old) underwent treatment with topical elastase or heat-inactivated elastase (control). Separate groups of mice were administered RvD1 (100ng/kg) or saline i.p. daily from day(d)1 to d13 and aortic diameter was measured by video micrometry on d14. mRNA quantification of FPR2 expression in aortic tissue was performed by RT-PCR on d7, 14 and 21. Human aortic tissue from AAA patients and controls (organ transplant donors) were analyzed for quantification of FPR2 expression. Data is presented as mean ± SEM and statistical analysis was performed by using Mann-Whitney test for phenotype or Wilcoxon Signed Rank Test for gene expression data. Results: Elastase-treated WT mice had significantly increased aortic diameter compared to controls (127±8% vs. 1± 0.6%; p-/- had a significant increase in aortic diameter compared to elastase-treated WT mice (165±16% vs. 127± 8%; p=0.03). RvD1 treatment attenuated AAA formation in WT mice, but not FPR2 -/- mice, on d14 (56± 10% vs.121± 8%; p-/- mice compared to WT mice, after respective treatments with RvD1. Elastase-treated WT mice had significantly increased FPR2 receptor mRNA expression compared to respective controls on d7, d14, and d21. Human AAA tissue demonstrated significantly decreased FPR2 mRNA expression compared to controls (p=0.02). Conclusions: This data identifies the role of FPR2 in dysregulation of inflammation-resolution during AAA pathogenesis. Immunomodulation of FPR2 signaling by exogenous RvD1 identifies a novel mechanism in resolution of aortic inflammation and vascular remodeling during AAA pathogenesis.

Solid particulate additives are sometimes used to promote the uniform growth of multiple hydraulic fractures in horizontal oil and gas wells. The principle is that solid particulates block, accumulate, and form larger porous plugging zones preferentially at entrances of fracture taking in the most fluid volume. These porous zones create fluid flow resistance or additional pressure loss; thereby, inhibiting the growth of these dominant fractures and diverting fluid to suppressed fractures. While this technology is promising, governing design parameters and ramifications of placing solids diverters inside the fracture remain unclear. This paper models the propagation of multi-fractures with diverter pressure losses induced by the porous plugging zones. The resulting non-linear hydraulic fracturing problem is solved numerically with an Implicit Level Set Algorithm (ILSA) for each time step and the mechanisms of diversion are illustrated by comparing and contrasting cases with and without particle diverter. In both cases, during the fluid ramp-up period (pumping rate gradually increases from 0 to fracturing rate (QT)), the injection can be equally distributed among fractures before the stress interference affects the fluid allocation (Phase I). Then, stress interference starts to partition more fluid into outer fractures and suppress the growth of the middle fracture (Phase II). Once the perforation friction loss is sufficient to counteract the stress interaction, injection begins to shift to the middle fracture, but still gives a significantly nonuniform fracture growth (Phase III). At this point, solid diverter particles are introduced, leading to three additional phases of growth. Phase IV introduces solid diverters to the treatment at a reduced pumping rate. Particles bridge, accumulate and create porous plugging zones at the flow entrance. A higher pressure drop in outer fractures diverts injection fluids to the middle fracture. Phase V resumes the treatment rate to QT without diverter. The increased pump rate in turn increases the pressure drop in outer fractures and diverts more fluids to the middle fracture. This results in a rapid extension velocity for the middle fracture, enabling it to have the chance to catch up with the longer outer fractures (in Phase VI). This process is controlled by the interplay among stress interference, perforation friction loss, and diverting pressure drop. These simulations demonstrate that a model-based optimization could improve the effectiveness of the diverter technology and promote a uniform multi-fracture growth.

Supply chain security (SCS) breaches are torturing supply chains and they have the potential to inflict acute pain on society at large. To cope with such breaches, international bodies, nations, societies, industries, and leading firms have instituted several countermeasures in the form of standards and respective practices. Identifying SCS practices suitable to a firm's specific needs from a laundry list of practices is a difficult task. Relying on the risk management literature and interactions with professionals, we categorize SCS management practices into four classes based on their intent—detection, prevention, response, and mitigation. We consider here their differences and their complementary effects. Our classification can be used to diagnose a firm's supply chain security status. Managers can benchmark their company against their peers using this classification. Equipped with such knowledge, managers, and organizations can ascertain specific gaps and undertake a targeted approach to bridge those gaps. Our results suggest that security-oriented practices have differential effects on SCS performance. We also found that firms who deploy practices in a more integrated approach realize better SCS performance. Thus, firms are advised to adopt the practices as a system to take advantage of the reinforcing characteristics of these practices on each other.

The specialized pro-resolving lipid mediator Maresin 1 (MaR1) is involved in the resolution phase of tissue inflammation. It was hypothesized that exogenous administration of MaR1 would attenuate abdominal aortic aneurysm (AAA) growth in a cytokine-dependent manner via LGR6 receptor signaling and macrophage-dependent efferocytosis of smooth muscle cells (SMCs). AAAs were induced in C57BL/6 wild-type (WT) mice and smooth muscle cell specific TGF-β2 receptor knockout (SMC-TGFβr2(−/−)) mice using a topical elastase AAA model. MaR1 treatment significantly attenuated AAA growth as well as increased aortic SMC α-actin and TGF-β2 expressions in WT mice, but not SMC-TGFβr2(−/−) mice, compared to vehicle-treated mice. In vivo inhibition of LGR6 receptors obliterated MaR1-dependent protection in AAA formation and SMC α-actin expression. Furthermore, MaR1 upregulated macrophage-dependent efferocytosis of apoptotic SMCs in murine aortic tissue during AAA formation. In vitro studies demonstrate that MaR1-LGR6 interaction upregulates TGF-β2 expression and decreases MMP2 activity during crosstalk of macrophage-apoptotic SMCs. In summary, these results demonstrate that MaR1 activates LGR6 receptors to upregulate macrophage-dependent efferocytosis, increases TGF-β expression, preserves aortic wall remodeling and attenuate AAA formation. Therefore, this study demonstrates the potential of MaR1-LGR6 mediated mitigation of vascular remodeling through increased efferocytosis of apoptotic SMCs via TGF-β2 to attenuate AAA formation.

Preclinical animal models of chronic kidney disease (CKD) are critical to investigate the underlying mechanisms of disease and to evaluate the efficacy of novel therapeutics aimed to treat CKD-associated pathologies. The objective of the present study was to compare the adenine diet and 5/6 nephrectomy (Nx) CKD models in mice. Male and female 10-wk-old C57BL/6J mice (n = 5–9 mice/sex/group) were randomly allocated to CKD groups (0.2−0.15% adenine-supplemented diet or 5/6 Nx surgery) or the corresponding control groups (casein diet or sham surgery). Following the induction of CKD, the glomerular filtration rate was reduced to a similar level in both adenine and 5/6 Nx mice (adenine diet-fed male mice: 81.1 ± 41.9 µL/min vs. 5/6 Nx male mice: 160 ± 80.9 µL/min, P = 0.5875; adenine diet-fed female mice: 112.9 ± 32.4 µL/min vs. 5/6 Nx female mice: 107.0 ± 45.7 µL/min, P = 0.9995). Serum metabolomics analysis indicated that established uremic toxins were robustly elevated in both CKD models, although some differences were observed between CKD models (i.e., p-cresol sulfate). Dysregulated phosphate homeostasis was observed in the adenine model only, whereas Ca(2+) homeostasis was disturbed in male mice with both CKD models. Compared with control mice, muscle mass and myofiber cross-sectional areas of the extensor digitorum longus and soleus muscles were ∼18−24% smaller in male CKD mice regardless of the model but were not different in female CKD mice (P > 0.05). Skeletal muscle mitochondrial respiratory function was significantly decreased (19−24%) in CKD mice in both models and sexes. These findings demonstrate that adenine diet and 5/6 Nx models of CKD have similar levels of renal dysfunction and skeletal myopathy. However, the adenine diet model demonstrated superior performance with regard to mortality (∼20−50% mortality for 5/6 Nx vs. 0% mortality for the adenine diet, P < 0.05 for both sexes) compared with the 5/6 Nx surgical model. NEW & NOTEWORTHY Numerous preclinical models of chronic kidney disease have been used to evaluate skeletal muscle pathology; however, direct comparisons of popular models are not available. In this study, we compared adenine-induced nephropathy and 5/6 nephrectomy models. Both models produced equivalent levels of muscle atrophy and mitochondrial impairment, but the adenine model exhibited lower mortality rates, higher consistency in uremic toxin levels, and dysregulated phosphate homeostasis compared with the 5/6 nephrectomy model.

Rationale: Blood eosinophil count and ECP (eosinophil cationic protein) associate with human cardiovascular diseases. Yet, whether eosinophils play a role in cardiovascular disease remains untested. The current study detected eosinophil accumulation in human and murine abdominal aortic aneurysm (AAA) lesions, suggesting eosinophil participation in this aortic disease. Objective: To test whether and how eosinophils affect AAA growth. Methods and Results: Population-based randomized clinically controlled screening trials revealed higher blood eosinophil count in 579 male patients with AAA than in 5063 non-AAA control (0.236±0.182 versus 0.211±0.154, 10 9 /L, P P P =0.031) logistic regression analyses indicated that increased blood eosinophil count in patients with AAA served as an independent risk factor of human AAA. Immunostaining and immunoblot analyses detected eosinophil accumulation and eosinophil cationic protein expression in human and murine AAA lesions. Results showed that eosinophil deficiency exacerbated AAA growth with increased lesion inflammatory cell contents, matrix-degrading protease activity, angiogenesis, cell proliferation and apoptosis, and smooth muscle cell loss using angiotensin-II perfusion–induced AAA in Apoe −/− and eosinophil-deficient Apoe −/− ΔdblGATA mice. Eosinophil deficiency increased lesion chemokine expression, muted lesion expression of IL (interleukin) 4 and eosinophil-associated-ribonuclease-1 (mEar1 [mouse EOS-associated-ribonuclease-1], human ECP homolog), and slanted M1 macrophage polarization. In cultured macrophages and monocytes, eosinophil-derived IL4 and mEar1 polarized M2 macrophages, suppressed CD11b + Ly6C hi monocytes, and increased CD11b + Ly6C lo monocytes. mEar1 treatment or adoptive transfer of eosinophil from wild-type and Il13 −/− mice, but not eosinophil from Il4 −/− mice, blocked AAA growth in Apoe −/− ΔdblGATA mice. Immunofluorescent staining and immunoblot analyses demonstrated a role for eosinophil IL4 and mEar1 in blocking NF-κB (nuclear factor-κB) activation in macrophages, smooth muscle cells, and endothelial cells. Conclusions: Eosinophils play a protective role in AAA by releasing IL4 and cationic proteins such as mEar1 to regulate macrophage and monocyte polarization and to block NF-κB activation in aortic inflammatory and vascular cells.

BACKGROUND: Female sex protects against abdominal aortic aneurysms (AAAs); however, the mechanisms behind these sex-based differences remain unknown. The purpose of this study was to explore the role of sex and sex hormones in AAA formation among swine. MATERIALS AND METHODS: Using a previous validated model, infrarenal AAA were surgically created in uncastrated male (n=8), female (n=5), and castrated male (n=4) swine. Aortic dilation was measured on post-operative day 28 during the terminal procedure and compared to initial aortic diameter measured during the index procedure. Tissue was analyzed for immunohistochemistry, cytokine array, gelatin zymography, serum 17β–Estradiol, and testosterone assay. RESULTS: Uncastrated males had significantly larger maximal aortic dilation compared to castrated males (113.5%±11.4% vs 38.1%±4.5%, p=.0012). Females had significantly higher mean aortic dilation compared to castrated males (96.2%±7.5% vs 38.1%±4.5%, p=.0004). Aortic diameters between females and uncastrated males were not significantly different on day 28. Female swine had significantly higher concentrations of 17β-estradiol compared with uncastrated males (1590±873.3 ng/mL vs 95.2±2.3 ng/mL, p=.047), with no significant difference between females and castrated males. Uncastrated male AAA demonstrated significantly more elastin degradation compared with female and castrated males (p=0.01 and

Modeling the simultaneous propagation of multiple hydraulic fractures is important for stimulation of horizontal oil and gas wells. A new numerical model for the initiation and subsequent propagation of multiple hydraulic fractures allows the fractures to propagate under subcritical conditions. Including subcritical growth enables demonstration of the importance of time-dependent hydraulic fracture initiation and its impact on the subsequent growth of multiple hydraulic fractures, indicating that this phenomenon can strongly impact the behavior of simultaneously-growing hydraulic fractures, including reducing the suppression of some fractures during growth and reducing the pressure required to sustain fracture propagation.

Objective Resolvins have been shown to attenuate inflammation, whereas NETosis, the process of neutrophils releasing neutrophil extracellular traps (NETs), produces increased inflammation. It is hypothesized that treatment of animals with resolvin D1 (RvD1) would reduce abdominal aortic aneurysm (AAA) formation by inhibiting NETosis. Methods Wild-type 8- to 12-week-old C57BL/6 male mice (n = 47) and apolipoprotein E-deficient (ApoE−/−) mice (n = 20) were used in two models to demonstrate the effects of RvD1 on AAA growth. In the topical elastase AAA model, wild-type mice were divided into three groups: a deactivated elastase control group, in which sham surgery was performed using deactivated elastase and mice were intravenously injected with phosphate-buffered saline (PBS) once a day until harvest; an elastase group, in which active elastase was used to induce AAA and mice were injected with PBS daily until harvest; and an RvD1-treated group, in which AAA was induced and mice were injected with RvD1 daily until harvest. In the angiotensin II (Ang II)-induced AAA model, ApoE−/− mice were fed a high-fat diet and implanted with osmotic infusion pumps containing Ang II (1000 ng/kg/min). The Ang II model was divided into two groups: an Ang II control group, in which Ang II was delivered and mice were injected with PBS daily until harvest; and an RvD1-treated group, in which Ang II was delivered and mice were injected with RvD1 daily until harvest. On postoperative day 3, day 14, or day 28, aortic and blood samples were collected for Western blot, histology, cytokine array, enzyme-linked immunosorbent assay, and gelatin zymography after aortic diameter measurement. Results The day 14 RvD1-treated group demonstrated 42% reduced AAA diameter compared with the elastase group (P Conclusions RvD1-mediated inhibition of NETosis may represent a future medical treatment for the attenuation of AAA growth.

Addressing endogeneity can be a challenging task given the different sources of endogeneity and their impacts on empirical results. While premier business journals typically expect authors to rigorously address endogeneity, this expectation is relatively new to many Operations Management (OM) scholars, as exemplified by a recent editorial in Journal of Operations Management that calls for more rigorous treatment for endogeneity. This study serves two purposes. First, we summarize recent OM literature with respect to the treatment for endogeneity by reviewing studies published in leading OM journals between 2012 and 2017. The review provides evidence that endogeneity problems have received increasing attention from OM scholars. However, we also find some common problems that may render the chosen techniques for addressing endogeneity less effective and potentially lead to biased analysis results. Second, since instrumental variable regression is the most prevalent technique for dealing with endogeneity in the OM literature according to our review, we provide an empirical illustration tailored to OM researchers for using instrumental variable regression in the post-design (data analysis) phase. Using variables from a publicly available healthcare dataset, our analysis sheds light on the importance of examining instruments' quality and triangulating results based on more than one test/estimator.

Earthquakes, mine failures, and initiation of hydraulic fractures have all been associated with time-delayed breakage of rocks subjected to loads insufficient to incur instantaneous failure. To better model and identify failure precursors for rocks under these so-called static fatigue conditions, Acoustic Emission (AE) was monitored in beams of Coldspring Charcoal Granite subjected to constant three point loading. As a result of varying the magnitude of the loading, the times to failure range from O ( 10 1 ) to O ( 10 5 ) seconds. The experiments show a number of consistencies in the AE data. In all cases the event rate exponentially declines for a period that is about 0.4–0.6 of the total time to failure. This period is followed by a period in which the event rate exponentially increases. The total number of events generated during these two periods is also consistent among the experiments. Motivated by these observations, we propose a modified kinetic fracture theory that captures both the period of event rate decline and the period of event rate increase. It does this by firstly accounting for early time depletion of available bonds for breakage, similar to previous models. The model also accounts for generation of critically stressed bonds in the vicinity of previous bond breakages due to stress redistribution, thereby also predicting the event rate increase and further providing consistency with the observed tendency of the events to become increasingly concentrated around the eventual plane of failure as time progresses.

Carbonate-rich rocks are commonly encountered in oil and gas reservoirs, and as such, mechanisms of hydraulic fracture initiation and growth in carbonates are important for effective reservoir stimulation. Thus motivated, this paper shows the impact of acidic fluid on the hydraulic fracture initiation in laboratory experiments. The results demonstrate that compared to water injection, acid injection results in more rapid initiation of the hydraulic fractures under so-called static fatigue or pressure-delay conditions wherein a certain pressure, insufficient to instantaneously generate a hydraulic fracture, is maintained until a hydraulic fracture grows. Acid injection also is shown to generate a dissolution cavity in the vicinity of the wellbore, and the breakdown of the specimen is observed to be explosive in the case of acid injection, probably due to the generation and the subsequent rapid expansion of carbon dioxide as a part of the dissolution reaction. Finally, the time to breakdown is shown to be related not only to the magnitude of the wellbore pressure, but also to the apparent permeability of the specimen. Altogether, the results indicate first that acid injection has the potential to improve the initiation of multiple hydraulic fractures within multistage hydraulic fracturing of horizontal wells by decreasing the time required for initiation at subcritical wellbore pressures. The results also show that the current theoretical framework can capture the overall negative exponential relationship between the time to breakdown and the wellbore pressure, but it is insufficient to account for the secondary dependence on rock permeability.

The formation of an abdominal aortic aneurysm (AAA) is characterized by inflammation, macrophage infiltration, and vascular remodeling. In this study, we tested the hypothesis that mesenchymal stromal cell (MSC)–derived extracellular vesicles (EVs) immunomodulate aortic inflammation, to mitigate AAA formation via modulation of microRNA-147. An elastase-treatment model of AAA was used in male C57BL/6 wild-type (WT) mice. Administration of EVs in elastase-treated WT mice caused a significant attenuation of aortic diameter and mitigated proinflammatory cytokines, inflammatory cell infiltration, an increase in smooth muscle cell α-actin expression, and a decrease in elastic fiber disruption, compared with untreated mice. A 10-fold up-regulation of microRNA (miR)-147, a key mediator of macrophage inflammatory responses, was observed in murine aortic tissue in elastase-treated mice compared with controls on d 14. EVs derived from MSCs transfected with miR-147 mimic, but not with miR-147 inhibitor, attenuated aortic diameter, inflammation, and leukocyte infiltration in elastase-treated mice. In vitro studies of human aortic tissue explants and murine-derived CD11b(+) macrophages induced proinflammatory cytokines after elastase treatment, and the expression was attenuated by cocultures with EVs transfected with miR-147 mimic, but not with miR-147 inhibitor. Thus, our findings define a critical role of MSC-derived EVs in attenuation of aortic inflammation and macrophage activation via miR-147 during AAA formation.—Spinosa, M., Lu, G., Su, G., Bontha, S. V., Gehrau, R., Salmon, M. D., Smith, J. R., Weiss, M. L., Mas, V. R., Upchurch, G. R., Sharma, A. K. Human mesenchymal stromal cell-derived extracellular vesicles attenuate aortic aneurysm formation and macrophage activation via microRNA-147.

Purpose Supply chain managers (SC managers) may make less than optimal decisions for the firm when facing compensation and employment risks. The purpose of this paper is to study two relevant factors (target setting and strategic importance of the supply chain function) that may drive SC managers to perceive more or less risk to their welfare. Design/methodology/approach The study combines survey data from 133 firms with secondary data in order to reduce source bias and enhance the validity of results. The authors also conducted interviews with supply chain and human resources managers. Findings The results show that top managers can alter SC managers’ perceived risks. Ambitious targets drive compensation risk but not employment risk. The supply chain function’s strategic importance, on the other hand, decreases employment risk but increases compensation risk. Research limitations/implications The authors emphasize two ways that the top management team (TMT) influences SC managers’ perceived personal welfare but acknowledge that there may be others factors. Due to the topic sensitivity, the authors could not collect data on all variables (e.g. individual characteristics) that may affect risk perception. The findings are based on Spanish firms and may not be generalized to other contexts. Practical implications This research proposes three suggestions. First, compensation and employment risks should be considered separately when designing compensation and evaluation systems. Second, appropriate performance targets may put compensation risk in a reasonable range that is neither too high to prevent risky-yet-beneficial decisions nor too low to allow nonfeasance. Third, escalating the supply chain’s strategic importance effectively offsets employment risk. Originality/value Scholars have repeatedly shown the negative outcomes of SC managers’ perceived compensation and employment risks. Yet, little attention has been given to their antecedents. The study explores two relevant antecedents and provides integrative empirical evidence regarding actions top leaders can take to manage SC managers’ perceived risk and subsequently enhance firm performance.

Supply chains have become increasingly complex in the last decade, which makes their structural characteristics important determinants of firm performance. Prior studies on supply chain structure have largely emphasized network-level attributes but ignored supply-base level characteristics. However, in many cases it is the 1 st tier suppliers, not those “deep in the network,” that have most immediate influence on the buyer. In addition, some structural characteristics, such as direct links between the buyer's suppliers and its customers, are not-so-visible to the buyer, yet can impact its financial performance dramatically. The existing literature has overlooked these not-so-visible structural links. Using objective supply chain data collected from Mergent Online and Compustat , we map the supply base structure of 867 public firms. We construct three visible (horizontal, vertical and spatial) and two not-so-visible (eliminative and cooperative) structural complexity metrics, and examine their impacts on buyer firms' financial performance as measured by Return on Assets and Tobin's Q. Our empirical analysis shows that the five dimensions have differential effects: some have negligible impacts while others appear to strongly affect financial performance. Contrary to the common belief that complexity hurts performance, we find that an individual complexity dimension may have both positive and negative effects, and the overall effect may be non-linear.

Supply chain security is a topic that received considerable attention over the last 16 years, especially after the September 11 attacks in the United States (U.S.). The devastation caused by the te...

Supply chain security (SCS) breaches in the food supply chains are distressing respective firms across the globe. They also have the potential of inflicting pain on the society at large. Despite the abundance of practices that have been advocated to cope with SCS breaches, the literature lacks a conceptual taxonomy to organize them. Classifying practices into respective taxa can advance theory building and stimulate the testing of substantive hypotheses. Toward this end, we develop a taxonomy which conceptually rests on the human immune system and its attempts to protect the human body from pathogens. We deploy a metaphorical transfer process and postulate that SCS practices can be classified into four classes based on their intent: prevention, detection, reaction, and restoration. We then discuss the implications of the taxonomy and assert that our taxonomy can be exploited to a variety of domains in the realm of risk management.

Supply chain security (SCS) breaches (a form of supply chain risk) are distressing supply chains and they have the potential to engender acute pain on the society at large. To counteract such breaches, international bodies, nations, societies, industries, and firms have instituted several countermeasures in the form of standards and respective practices. Given that not all incidences/breaches can be averted, the risk management literature advocates that firms should adopt practices that can thwart incidences/breaches and practices that can provide a swift response once an incident/breach is detected in order to contain damages, ease the pain, and restore operations. Resting on the risk management literature and interactions with professionals, we classify SCS management practices into four categories based on their intent (i.e., detection, prevention, response, and mitigation) and operationalize each via multiple indicators. We then test the relative efficacy of these practices to explain SCS performance using responses from 462 firms operating in the United States and Italy.

A numerical model has been developed for simulating the initiation and propagation of a plane strain or axisymmetric hydraulic fracture from an openhole wellbore in an impermeable homogeneous rock formation. The main novelty is inclusion of a subcritical growth law, thereby allowing consideration of hydraulic fracture growth when the wellbore pressure is otherwise considered insufficient to initiate fracturing. To enable tracking the moving crack front in the simulations, we develop a new tip asymptotics based on a subcritical crack growth law. The results are first validated against available analytical solutions for plane strain and axisymmetric hydraulic fractures. A comparison is presented between the solutions of the subcritical growth model and a conventional hydraulic fracture model in which fracture growth is not allowed until the stress intensity factor equals the fracture toughness of the rock. This comparison, as well as a study of the influence of the relevant parameters appearing in the subcritical growth law, indicates significant influence of subcritical growth on the evolution of the crack length and the wellbore pressure. Notably, this model provides the capability to simulate delayed growth of hydraulic fractures under pressures that are insufficient to generate instantaneous growth, which is a behavior observed in experiments but not considered by conventional hydraulic fracturing models.

This study examines the effect of delivery performance on customer transactions. We propose that different delivery performance dimensions (on-time delivery rate, early delivery inaccuracy, late delivery inaccuracy, and delivery speed) have varying impacts on future customer transaction quantities and unit prices. We further explore the effect of customer types on the proposed relationships. Trade customers (resellers) and Original Equipment Manufacturer (OEM) customers generally have different operational needs for deliveries and therefore may value these metrics differently. Using instrumental variable regression, we analyze a proprietary transaction-level dataset. The information was compiled by a Fortune 500 manufacturer from its Heating, Ventilation and Air Conditioning (HVAC) control product supply chain, consisting of the manufacturer and its customers. The results indicate that measures of delivery performance affect customer transaction quantity and unit price differently. Furthermore, these impacts can differ significantly between trade customers and OEM customers. These findings provide fine-grained insights about tuning delivery capabilities to increase sales volume or boost price.

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called β-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease. Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone. Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% ± 47.4% at day 7, 105.4% ± 58.1% at day 14, and 113.5% ± 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p < 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease. Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. An aneurysm forms as a result of progressive weakening and eventual dilation of the aorta, which can rupture or tear once it reaches a critical diameter. Aneurysms of the descending aorta in the chest, called descending thoracic aortic aneurysms (dTAA), make up a large proportion of aneurysm cases in the United States. Uncontained dTAA rupture is almost universally lethal, and elective repair has a high rate of morbidity and mortality. The purpose of our model is to study dTAA specifically, to elucidate the pathophysiology of dTAA and to search for molecular targets to halt the growth or reduce the size of dTAA. By having a murine model to study thoracic pathology precisely, targeted therapies can be developed to specifically test dTAA. The method is based on the placement of porcine pancreatic elastase (PPE) directly on the outer murine aortic wall after surgical exposure. This creates a destructive and inflammatory reaction, which weakens the aortic wall and allows for aneurysm formation over weeks to months. Though murine models possess limitations, our dTAA model produces robust aneurysms of predictable size. Furthermore, this model can be used to test genetic and pharmaceutical targets which may arrest dTAA growth or prevent rupture. In human patients, interventions such as these could help avoid aneurysm rupture, and difficult surgical intervention.

Aims Obesity is a risk factor of abdominal aortic aneurysm (AAA). Inflammatory cytokine interleukin-18 (IL18) has two receptors: IL18 receptor (IL18r) and Na-Cl co-transporter (NCC). In human and mouse AAA lesions, IL18 colocalizes to its receptors at regions rich in adipocytes, suggesting a role of adipocytes in promoting IL18 actions in AAA development. Methods and results We localized both IL18r and NCC in human and mouse AAA lesions. Murine AAA development required both receptors. In mouse AAA lesions, IL18 binding to these receptors increased at regions enriched in adipocytes or adjacent to perivascular adipose tissue. 3T3-L1 adipocytes enhanced IL18 binding to macrophages, aortic smooth muscle cells (SMCs), and endothelial cells by inducing the expression of both IL18 receptors on these cells. Adipocytes also enhanced IL18r and IL18 expression from T cells and macrophages, AAA-pertinent protease expression from macrophages, and SMC apoptosis. Perivascular implantation of adipose tissue from either diet-induced obese mice or lean mice but not that from leptin-deficient ob/ob mice exacerbated AAA development in recipient mice. Further experiments established an essential role of adipocyte leptin and fatty acid-binding protein 4 (FABP4) in promoting IL18 binding to macrophages and possibly other inflammatory and vascular cells by inducing their expression of IL18, IL18r, and NCC. Conclusion Interleukin-18 uses both IL18r and NCC to promote AAA formation. Lesion adipocyte and perivascular adipose tissue contribute to AAA pathogenesis by releasing leptin and FABP4 that induce IL18, IL18r, and NCC expression and promote IL18 actions.

Shale is typically an anisotropic material for which the mechanical characteristics can vary significantly along different orientations with regard to its bedding planes. In underground formations, the strength of shale shows strong dependence on the pre-existing weaknesses and the water content. This study is concerned with the mechanical behavior of Marcellus shale specimens under three-point bending where loading is applied in different directions with respect to its bedding plane orientation under both dry and saturated conditions. Acoustic Emission (AE) is recorded in order to investigate the nucleation of microfracturing via AE locations and Moment Tensor Analysis (MTA). Complimentary to the AE detection and analysis, X-ray Computed Tomography (CT) is utilized to image internal damage sustained due to loading. Experimental results show lower nominal tensile strength when bending loads are applied parallel to bedding in dry samples. Further comparisons between tests under different conditions point to the strong impact of the pore water and pre-existing weaknesses on the samples. Detailed results from MTA show tensile microfracturing is the dominant crack type. Surprisingly, event locations show a large number of AE events occur in areas of the beam that are nominally subjected to compressive stress, implying that fracturing can be strongly impacted by local stress fluctuations which may result in opening of the interfaces between bedding layers even when the nominal stress in an area is compressive. In several cases, AE associate with visible fractures in the CT scan which are not connected to the main rupture surface through the specimen. Additionally, visualization of the internal fracture paths using image segmentation on the CT results show more complex fracture systems in parallel loading cases, which brings together localized fractures generated by different mechanisms.

This article develops a theoretical conceptualization of supply chain uncertainty, based on the foundation provided by contingency theory, classical organization theory, and information processing theory. We develop a theoretical analogy between a supply chain and an organization, then highlight key differences, which leads us to hypothesize that there are three key types of supply chain uncertainty. Micro-level uncertainty is based on the variability of inputs to the technical core of a supply chain, corresponding to the traditional operationalization of uncertainty in the supply chain and operations management literature. Meso-level uncertainty is the lack of information needed by a supply chain member, corresponding to the information processing theory perspective. This is often due to the conflicting pressures of differentiation and interdependence in a supply chain, where members may withhold information that they feel could compromise their interests. Macro-level uncertainty, based on the equivocality construct, is related to unclear and ambiguous situations faced by supply chain members in rapidly changing external environments. We propose that all three types of uncertainty coexist in a supply chain and may interact with each other. Based on contingency theory's focus on alignment of process and structure with the environment, we test the relationship among supply chain integration (process), centralization, formalization and flatness (organization structure) and the dimensions of uncertainty (environment). Hypotheses are tested using hierarchical regression on data collected from 339 globally distributed manufacturing plants. It reveals that, as hypothesized, micro-level and meso-level uncertainty are positively related to SCI and that macro-level uncertainty is inversely related to it. The organization structure variables of centralization and formalization had a moderating effect, strengthening or reducing the main effects of uncertainty. The results are discussed in terms of their consistency with the theoretical foundation, implications for decision makers facing supply chain uncertainty and future research opportunities.

Background Tamsulosin, an α1A-adrenergic receptor inhibitor, is prescribed to treat benign prostatic hyperplasia in men >60 years of age, the same demographic most susceptible to abdominal aortic aneurysm. The goal of this study was to investigate the effect of tamsulosin on abdominal aortic aneurysm pathogenesis. Methods Abdominal aortic aneurysms were induced in WT C57BL/6 male mice (n = 9-18/group), using an established topical elastase abdominal aortic aneurysm model. Osmotic pumps were implanted in mice 5 days before operation to create the model, administering either low dose (0.125 µg/day tamsulosin), high dose (0.250µg/day tamsulosin), or vehicle treatments with and without topical application of elastase. Blood pressures were measured preoperatively and on postoperative days 0, 3, 7, and 14. On postoperative day 14, aortic diameter was measured before harvest. Sample aortas were prepared for histology and cytokine analysis. Results Measurements of systolic blood pressure did not differ between groups. Mice treated with the low dose of tamsulosin and with the high dose of tamsulosin showed decreased aortic diameter compared with vehicle-treated control (93% ± 24 versus 94% ± 30 versus 132% ± 24, respectively; P = .0003, P = .0003). Cytokine analysis demonstrated downregulation of pro-inflammatory cytokines in both treatment groups compared with the control (P Conclusion Tamsulosin attenuates abdominal aortic aneurysm formation with increased preservation of elastin and decreased production of pro-inflammatory cytokines. Further studies are necessary to elucidate the mechanism by which tamsulosin attenuates abdominal aortic aneurysm pathogenesis.