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While the effects of immigrants on aggregate trade flows have been extensively examined, the role of immigrants in shaping trade in value added (TiVA) remains underexplored. Employing a panel dataset covering 38 Organization for Economic Co-operation and Development (OECD) member host countries and 64 immigrant home countries spanning 2000–2018 and estimating a random intercept and random slope mixed-effects model, we find that immigrants play a significant role in enhancing the value added from their home countries that is embedded in their host countries’ exports to the world. We document these effects at the aggregate level and across sectors (i.e., manufacturing, agriculture, and services). There is, however, considerable variation in the influence of immigrants on TiVA across country pairs. Our findings highlight that immigrants significantly enhance trade sophistication by promoting specialization and upward movement in the value chain, yielding economic benefits for their home and host countries.

Ac-hE18A-NH2 is a dual-domain apoE mimetic peptide that possesses the putative receptor binding domain from apoE (LRKLRKRLLR, denoted hE; residues 141–150) covalently attached to lipid-associating peptide 18A. Like apoE, Ac-hE18A-NH2 reduces plasma cholesterol in animal models and exhibits anti-inflammatory properties independent of its cholesterol-reducing effect. Ac-hE18A-NH2 has already undergone phase I clinical trials as a lipid-lowering agent. To explore the therapeutic potential more, we designed and synthesized new analogues by linking ɑ-aminohexanoic acid, octanoic acid, or myristic acid to LRRLRRRLLR-18A-NH2 ([R]hE18A-NH2) and examined the cholesterol-lowering potency in animals. The modified peptides effectively reduced plasma cholesterol in apoE-null mice fed standard chow or a Western diet; the myristyl analogue was the most effective. A single administration of the myristyl analogue reduced plasma total and LDL cholesterol in a dose-dependent manner in hypercholesterolemic cynomolgus macaques for up to 1 week despite the continuation of a cholesterol-supplemented diet. The myristyl peptide (7.4 mg/kg) reduced total and LDL cholesterol at 24 h by 64% and 74%, respectively; plasma HDL levels were modestly reduced and returned to baseline by day 7. These new analogues should exhibit enhanced potency at lower doses than Ac-hE18A-NH2, which may make them attractive therapeutic candidates for clinical trials.

Obesity has achieved epidemic status in the United States, resulting in an increase in type 2 diabetes mellitus, dyslipidemia, and cardiovascular disease. Numerous studies have shown that inflammation plays a key role in the development of insulin resistance and diabetic complications. HDL cholesterol levels are inversely associated with coronary heart disease in humans. The beneficial effect of HDL is due, in part, to apolipoproteins A-I and E, which possess anti-inflammatory properties. The functional quality of HDL, however, may be reduced in the context of diabetes. Thus, raising levels of functional HDL is an important target for reducing inflammation and diabetic complications. Apo A-I possesses eight alpha-helical sequences, most of which form class A amphipathic helical structures. Peptides belonging to this class inhibit atherogenesis in several mouse models. Additional peptides based on structural components of apoE have been shown to mediate a rapid clearance of atherogenic lipoproteins in dyslipidemic mice. In this review, we discuss the efficacy of apolipoprotein mimetic peptides in improving lipoprotein function, reducing inflammation, and reversing insulin resistance and cardiometabolic disease processes in diabetic animals.

Excessive inflammation after myocardial infarction (MI) can promote infarct expansion and adverse left ventricular (LV) remodeling. L-4F, a mimetic peptide of apolipoprotein A-I (apoA-I), exhibits anti-inflammatory and anti-atherogenic properties; however, whether L-4F imparts beneficial effects after myocardial infarction (MI) is unknown. Here we demonstrate that L-4F suppresses the expansion of blood, splenic, and myocardial pro-inflammatory monocytes and macrophages in a mouse model of reperfused MI. Changes in immune cell profiles were accompanied by alleviation of post-MI LV remodeling and dysfunction. In vitro, L-4F also inhibited pro-inflammatory and glycolytic gene expression in macrophages. In summary, L-4F treatment prevents prolonged and excessive inflammation after MI, in part through modulation of pro-inflammatory monocytes and macrophages, and improves post-MI LV remodeling. These data suggest that L-4F could be a used as a therapeutic adjunct in humans with MI to limit inflammation and alleviate the progression to heart failure.

Subarachnoid hemorrhage (SAH) may present with cardiac arrest (SAH-CA). We report a case of SAH-CA to assist providers in distinguishing SAH as an etiology of cardiac arrest despite electrocardiogram findings that may be suggestive of a cardiac etiology. SAH-CA is associated with high rates of return of spontaneous circulation, but overall poor outcome. An initially non-shockable cardiac rhythm and the absence of brain stem reflexes are important clues in indentifying SAH-CA.

Reduced levels of HDL cholesterol (HDL-C) are a strong independent predictor of coronary artery disease (CAD) risk. The major anti-atherogenic function of HDL is to mediate reverse cholesterol transport. This response is highly dependent on apoA-I and apoE, protein components of HDL. Randomized clinical trials have assessed effects of several classes of drugs on plasma cholesterol levels in CAD patients. Agents including cholestyramine, fibrates, niacin, and statins significantly lower LDL cholesterol (LDL-C) and induce modest increases in HDL-C, but tolerance issues and undesirable side effects are common. Additionally, residual risk may be present in patients with persistently low HDL-C and other complications despite a reduction in LDL-C. These observations have fueled interest in the development of new pharmacotherapies that positively impact circulating lipoproteins. The goal of this review is to discuss the therapeutic potential of synthetic apolipoprotein mimetic peptides. These include apoA-I mimetic peptides that have undergone initial clinical assessment. We also discuss newer apoE mimetics that mediate the clearance of atherogenic lipids from the circulation and possess anti-inflammatory properties. One of these (AEM-28) has recently been given orphan drug status and is undergoing clinical trials.

Myeloperoxidase (MPO)-derived hypochlorous acid induces changes in HDL function via redox modifications at the level of apolipoprotein A-I (apoA-I). As 4F and apoA-I share structural and functional properties, we tested the hypothesis that 4F acts as a reactive substrate for hypochlorous acid (HOCl). 4F reduced the HOCl-mediated oxidation of the fluorescent substrate APF in a concentration-dependent manner (ED50∼ 56 ± 3 μM). This reaction induced changes in the physical properties of 4F. Addition of HOCl to 4F at molar ratios ranging from 1:1 to 3:1 reduced 4F band intensity on SDS-PAGE gels and was accompanied by the formation of a higher molecular weight species. Chromatographic studies showed a reduction in 4F peak area with increasing HOCl and the formation of new products. Mass spectral analyses of collected fractions revealed oxidation of the sole tryptophan (Trp) residue in 4F. 4F was equally susceptible to oxidation in the lipid-free and lipid-bound states. To determine whether Trp oxidation influenced its apoA-I mimetic properties, we monitored effects of HOCl on 4F-mediated lipid binding and ABCA1-dependent cholesterol efflux. Neither property was altered by HOCl. These results suggest that 4F serves as a reactive substrate for HOCl, an antioxidant response that does not influence the lipid binding and cholesterol effluxing capacities of the peptide.

High density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) reduce inflammatory responses to lipopolysaccharide (LPS). We tested the hypothesis that the apoA-I mimetic peptide 4F prevents LPS-induced defects in blood pressure and vascular reactivity. Systolic blood pressure (SBP) was measured in rats at baseline and 6 h after injection of LPS (10 mg/kg) or saline vehicle. Subgroups of LPS-treated rats also received 4F (10 mg/kg) or scrambled 4F (Sc-4F). LPS administration reduced SBP by 35% compared with baseline. 4F attenuated the reduction in SBP in LPS-treated rats (17% reduction), while Sc-4F was without effect. Ex vivo studies showed a reduced contractile response to phenylephrine (PE) in aortae of LPS-treated rats (ED50= 459 ± 83 nM) compared with controls (ED50= 57 ± 6 nM). This was associated with nitric oxide synthase 2 (NOS2) upregulation. 4F administration improved vascular contractility (ED50= 60 ± 9 nM), reduced aortic NOS2 protein, normalized plasma levels of NO metabolites, and reduced mortality in LPS-treated rats. These changes were associated with a reduction in plasma endotoxin activity. In vivo administration of 14C-4F and Bodipy-LPS resulted in their colocalization and retention in the HDL fraction. It is proposed that 4F promotes the localization of LPS to the HDL fraction, resulting in endotoxin neutralization. 4F may thus prevent LPS-induced hemodynamic changes associated with NOS2 induction.

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Cellular automata provide a high-resolution representation of urban spatial dynamics.Consequently they give the most realistic predictions of urban structural evolution, and in particular they are able to replicate the various fractal dimensionalities of actual cities. However, since these models do not readily incorporate certain phenomena like density measures and long-distance (as opposed to neighbourhood) spatial interactions, their performance may be enhanced by integrating them with other types of urban models.Cellular automata based models promise deeper theoretical insights into the nature of cities as self-organizing structures.