118 research outputs found
Stochastic Cyclic Inventory Routing with Supply Uncertainty: A Case in Green-Hydrogen Logistics
Hydrogen can be produced from water, using electricity. The hydrogen can
subsequently be kept in inventory in large quantities, unlike the electricity
itself. This enables solar and wind energy generation to occur asynchronously
from its usage. For this reason, hydrogen is expected to be a key ingredient
for reaching a climate-neutral economy. However, the logistics for hydrogen are
complex. Inventory policies must be determined for multiple locations in the
network, and transportation of hydrogen from the production location to
customers must be scheduled. At the same time, production patterns of hydrogen
are intermittent, which affects the possibilities to realize the planned
transportation and inventory levels. To provide policies for efficient
transportation and storage of hydrogen, this paper proposes a parameterized
cost function approximation approach to the stochastic cyclic inventory routing
problem. Firstly, our approach includes a parameterized mixed integer
programming (MIP) model which yields fixed and repetitive schedules for vehicle
transportation of hydrogen. Secondly, buying and selling decisions in case of
underproduction or overproduction are optimized further via a Markov decision
process (MDP) model, taking into account the uncertainties in production and
demand quantities. To jointly optimize the parameterized MIP and the MDP model,
our approach includes an algorithm that searches the parameter space by
iteratively solving the MIP and MDP models. We conduct computational
experiments to validate our model in various problem settings and show that it
provides near-optimal solutions. Moreover, we test our approach on an
expert-reviewed case study at two hydrogen production locations in the
Netherlands. We offer insights for the stakeholders in the region and analyze
the impact of various problem elements in these case studies
Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1
Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 Β΅M) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1β100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression
RNA profiling of cyclooxygenases 1 and 2 in colorectal cancer
Cyclooxygenases (particularily Cox-2) are involved in carcinogenesis and metastatic cancer progression. The expression profiles of the cyclooxygenases and the roles they play in established tumours of similar stage remains unclear. We report that Cox-1 and Cox-2 expression is highly variable in Dukes' C tumours, and changes in Cox-1 expression may be of importance
Obesity and Fatty Acids Promote Mitochondrial Translocation of STAT3 Through ROS-Dependent Mechanisms
Obesity promotes the onset and progression of metabolic and inflammatory diseases such as type 2 diabetes. The chronic low-grade inflammation that occurs during obesity triggers multiple signaling mechanisms that negatively affect organismal health. One such mechanism is the persistent activation and mitochondrial translocation of STAT3, which is implicated in inflammatory pathologies and many types of cancers. STAT3 in the mitochondria (mitoSTAT3) alters electron transport chain activity, thereby influencing nutrient metabolism and immune response. PBMCs and CD4+ T cells from obese but normal glucose-tolerant (NGT) middle-aged subjects had higher phosphorylation of STAT3 on residue serine 727 and more mitochondrial accumulation of STAT3 than cells from lean subjects. To evaluate if circulating lipid overabundance in obesity is responsible for age- and sex-matched mitoSTAT3, cells from lean subjects were challenged with physiologically relevant doses of the saturated and monounsaturated fatty acids, palmitate and oleate, respectively. Fatty acid treatment caused robust accumulation of mitoSTAT3 in all cell types, which was independent of palmitate-induced impairments in autophagy. Co-treatment of cells with fatty acid and trehalose prevented STAT3 phosphorylation and mitochondrial accumulation in an autophagy-independent but cellular peroxideβdependent mechanism. Pharmacological blockade of mitoSTAT3 either by a mitochondria-targeted STAT3 inhibitor or ROS scavenging prevented obesity and fatty acidβinduced production of proinflammatory cytokines IL-17A and IL-6, thus establishing a mechanistic link between mitoSTAT3 and inflammatory cytokine production
Baicalin Downregulates Porphyromonas gingivalis Lipopolysaccharide-Upregulated IL-6 and IL-8 Expression in Human Oral Keratinocytes by Negative Regulation of TLR Signaling
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Deep Sequencing of the Oral Microbiome Reveals Signatures of Periodontal Disease
The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (βΌ2 lanes Illumina 76 bp PE) and high human DNA contamination (up to βΌ90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes
Use of amnionβderived cellular cytokine solution for the treatment of gingivitis: A 2βweek safety, doseβranging, proofβofβprinciple randomized trial
Effects of periodontal disease on glycemic control, complications, and incidence of diabetes mellitus
Diabetes mellitus is a group of metabolic disorders with high mortality and morbidity associated with complications such as cardiovascular disease, kidney disease, and stroke. The prevalence of diabetes is 9.4% in US adults, and prevalence increases markedly with age, with 1 in 4 adults aged β₯65 years affected by diabetes. The estimated number of adults with type 2 diabetes globally almost tripled between 2002 and 2017, reflecting increases seen in the USA and elsewhere. This increase raises concerns about the increased morbidity and mortality associated with the complications of diabetes, including periodontal disease and tooth loss. There is a reciprocal adverse relationship between diabetes and periodontal disease, with diabetes as a major risk factor for periodontal disease, and in those patients with diabetes who also have periodontal disease then there are adverse effects on glycemic control and complications such as cardiovascular disease and end stage renal disease. In this review, those studies detailing the adverse effects of periodontal disease and diabetes will be discussed. Also, evidence is accumulating that periodontitis may play a role in increasing the incidence of new cases of type 2 diabetes, and possibly gestational diabetes. Of course, these studies need to be expanded to better understand the effects of periodontitis on diabetes glycemic control, complications, prediabetes, and the incidence of new cases. However, given the tremendous burden of diabetes on society, the dental profession should be proactive in preventing and treating periodontal disease, not only to preserve the dentition, but also to minimize the adverse effects of periodontitis on diabetes and its complications
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