Journal Production Guidance for Software and Data Citations.

Software and data citation are emerging best practices in scholarly communication. This article provides structured guidance to the academic publishing community on how to implement software and data citation in publishing workflows. These best practices support the verifiability and reproducibility of academic and scientific results, sharing and reuse of valuable data and software tools, and attribution to the creators of the software and data.

On the origin of nonequivalent states: How we can talk about preprints.

Increasingly, preprints are at the center of conversations across the research ecosystem. But disagreements remain about the role they play. Do they "count" for research assessment? Is it ok to post preprints in more than one place? In this paper, we argue that these discussions often conflate two separate issues, the history of the manuscript and the status granted it by different communities.

Potent quinoxaline-based inhibitors of PDGF receptor tyrosine kinase activity. Part 2: the synthesis and biological activities of RPR127963 an orally bioavailable inhibitor.

RPR127963 demonstrates an excellent pharmacokinetic profile in several species and was found to be efficacious in the prevention of restenosis in a Yucatan mini-pig model upon oral administration of 1-5 mg/kg. The in vitro selectivity profile and SAR of the highly optimized PDGF-R tyrosine kinase inhibitor are highlighted.

Potent quinoxaline-based inhibitors of PDGF receptor tyrosine kinase activity. Part 1: SAR exploration and effective bioisosteric replacement of a phenyl substituent.

Novel substituted 2-anilino- and 2-cycloalkylaminoquinoxalines have been found to be useful and selective inhibitors of PDGF-R autophosphorylation. Replacement of an anilino-substituent with substituted cyclohexylamino- or norbornylamino substituents led to significant improvements in the pharmacokinetic profile of these analogues.

Stent-induced restenosis in the swine coronary artery is inhibited by a platelet-derived growth factor receptor tyrosine kinase inhibitor, TKI963.

Activities of vascular smooth muscle cells (SMCs) such as proliferation, migration, and matrix production contribute to restenosis following clinical interventions of angioplasty and stent placement. Because activation of platelet-derived growth factor (PDGF)-receptor tyrosine kinase (PDGFr-TK) influences these processes and promotes restenosis, TKI963, an inhibitor of the PDGFr-TK was discovered, and its efficacy was evaluated in blocking stent-induced restenosis as analyzed by intravascular ultrasound (IVUS). TKI963, a low-molecular-weight compound, inhibited the cell-free PDGFbetar-TK with a K(i) value of 56 +/- 14 nM.

Intravascular ultrasound analysis of arterial remodeling in the double-injury swine coronary artery model of restenosis.

Background: Vascular remodeling is a major component of atherosclerotic and restenotic processes. The aim of this study was to evaluate remodeling at two different axial loci in a restenotic (double-injury) coronary artery model in the hypercholesterolemic minipig.

Methods: The cross-sectional area (CSA) of the lumen, artery and neointima following a single stenotic injury (SI) and second restenotic injury (RI) was measured by serial intravascular ultrasound (IVUS).

A potent PPARalpha agonist stimulates mitochondrial fatty acid beta-oxidation in liver and skeletal muscle.

The proposed mechanism for the triglyceride (TG) lowering by fibrate drugs is via activation of the peroxisome proliferator-activated receptor-alpha (PPARalpha). Here we show that a PPARalpha agonist, ureido-fibrate-5 (UF-5), approximately 200-fold more potent than fenofibric acid, exerts TG-lowering effects (37%) in fat-fed hamsters after 3 days at 30 mg/kg. In addition to lowering hepatic apolipoprotein C-III (apoC-III) gene expression by approximately 60%, UF-5 induces hepatic mitochondrial carnitine palmitoyltransferase I (CPT I) expression.

Restenosis following angioplasty in the swine coronary artery is inhibited by an orally active PDGF-receptor tyrosine kinase inhibitor, RPR101511A.

Background: Platelet-derived growth factor (PDGF), a purported mediator of arterial response to injury, stimulates proliferation, chemotaxis, and matrix production by activation of its membrane receptor tyrosine kinase. Because these activities underlie restenosis, inhibition of the PDGF-receptor tyrosine kinase (PDGFr-TK) is postulated to decrease restenosis.

Methods And Results: RPR101511A is a novel compound which selectively and potently inhibits the cell-free and in situ PDGFr-TK and PDGFr-dependent proliferation and chemotaxis in vascular smooth muscle cells (VSMC).

RPR 107393, a potent squalene synthase inhibitor and orally effective cholesterol-lowering agent: comparison with inhibitors of HMG-CoA reductase.

Squalene synthase catalyzes the reductive dimerization of two molecules of farnesyl pyrophosphate to form squalene and is the first committed step in sterol synthesis. A specific inhibitor of squalene synthase would inhibit cholesterol biosynthesis but not prevent the formation of other products of the isoprenoid pathway, such as dolichol and ubiquinone. RPR 107393 [3-hydroxy-3-[4-(quinolin-6-yl)phenyl]-1-azabicyclo[2-2-2]octane dihydrochloride] and its R and S enantiomers are potent inhibitors of rat liver microsomal squalene synthase, with IC50 values of 0.

1-Hydroxy-3-(methylpentylamino)-propylidene-1,1-bisphosphonic acid as a potent inhibitor of squalene synthase.

Squalene synthase, the first committed enzyme for sterol synthesis, converts farnesyl pyrophosphate to squalene with presqualene pyrophosphate as an intermediate. It was discovered that BM 21.0955 (1-hydroxy-3-(methylpentylamino)-propylidene-1,1-bisphosphon ic acid), in development for the treatment of bone disorders, inhibited rat liver microsomal squalene synthase (K(i) = nmol/l).

RPR 101821, a new potent cholesterol-lowering agent: inhibition of squalene synthase and 7-dehydrocholesterol reductase.

RPR 101821 (trans-2-[4-(benzoxazol-2-yl)-phenylmethoxy] amino cyclohexane hydrochloride) is a potent cholesterol-lowering agent in rodents and marmoset. The compound inhibited rat liver microsomal squalene synthase (IC50 = 1 nM) and 7-dehydrocholesterol (7DHC) reductase (IC50 = 1 microM; Lewis et al. 1995).

Enzyme inhibition during the conversion of squalene to cholesterol.

Two separate enzymatic assays were developed in order to test the selectivity of inhibitors in cholesterol biosynthesis. One assay detects inhibition of delta 5.7-sterol delta 7-reductase, the enzyme involved in the conversion of 7-dehydrocholesterol to cholesterol.

Characterization and inhibition of 15-lipoxygenase in human monocytes: comparison with soybean 15-lipoxygenase.

These studies characterized a method to measure 15-lipoxygenase (15-LO) activity in human monocytes (HMC) exposed to interleukin-4 (IL-4) and compare the activity with that of soybean 15-LO. 15-LO activity was quantitated by measuring 15-[14C]hydroxyeicosa-5Z,8Z,11Z,13E-tetraenoic acid (15-HETE) production from the substrate [14C]arachidonic acid (AA) after high-performance liquid chromatographic or thin-layer chromatographic separation. 15-HETE production by HMC was significantly elevated after continuous exposure to a single dose (10 ng/ml) of IL-4 for 4 days, was maximal at 5 days, and remained elevated at 6 days.

Electrode cuff-induced changes in DNA and PDGF gene expression in the rat carotid artery.

Low current (0.25, 3 mA) stimulation through a miniature electrode cuff encased around the carotid artery of the rat was used to induce intimal hyperplasia, an important feature of the atherosclerotic plaque and a phenomenon limiting the long term success of angioplasty. Compared to contralateral unstimulated arteries, 11-14 days of daily transmural stimulation of cuffed arteries (20 min period) significantly increased the amount of extracted DNA (diphenylamine colorimetric assay).

Modulation of vascular reactivity by vasoactive peptides in aortic rings from hypercholesterolemic rabbits.

The effect of moderate elevation in serum cholesterol on vascular reactivity to epidermal growth factor (EGF), endothelin (ET-1) and thrombin, vasoactive peptides present at sites of vascular injury, was examined in isolated aortic rings from rabbits fed either a casein-rich or a control diet for 10-12 weeks. In rings from hypercholesterolemic rabbits, development of maximal isometric tension to all peptide agonists was increased 22 +/- 0.6% while the EC50 for contraction was decreased.

Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis.

Some bisphosphonates used for the treatment of bone disorders are also potent inhibitors of squalene synthase, a critical enzyme for sterol biosynthesis. Among seven drugs tested, YM 175 (cycloheptylaminomethylene-1,1-bisphosphonic acid) was the most potent inhibitor of rat liver microsomal squalene synthase (Ki = 57 nM) and sterol biosynthesis from [14C]mevalonate in rat liver homogenate (IC50 = 17 nM). EB 1053 (3-(1-pyrolidino)-1-hydroxypropylidene-1,1-bisphosphonic acid) and PHPBP (3-(1-piperidino)-1-hydroxypropylidene-1,1-bisphosphonic acid) were less potent inhibitors in both these assays.

Tyrphostins inhibit PDGF-induced DNA synthesis and associated early events in smooth muscle cells.

Tyrphostins are low-molecular-weight synthetic inhibitors of protein tyrosine kinase, which block cell proliferation. Since platelet-derived growth factor (PDGF) is thought to figure prominently in disorders of vascular smooth muscle cells (VSMC), such as atherosclerosis, hypertension, and restenosis, we examined whether tyrphostins would inhibit PDGF-induced mitogenesis in VSMC. In this communication, we demonstrate that tyrphostins with the benzenemalononitrile nucleus inhibited PDGF-dependent growth of VSMC as well as PDGF-dependent DNA synthesis in these cells, with the concentrations for 50% inhibition ranging from 0.

Differential alteration of vascular reactivity in rabbit aorta with modest elevation of serum cholesterol.

The effect of diet-induced, moderate elevation of serum cholesterol on vascular reactivity in isolated rabbit abdominal aortic rings was examined by using a series of vasoconstrictor and vasodilator agonists. Serum cholesterol of rabbits that were fed a cholesterol-free, casein-rich diet for 10 weeks was elevated approximately 4.5-fold compared with values found in control rabbits that were fed standard lab chow (223 +/- 41 versus 51 +/- 5 mg/dl, respectively).

Phorbol-12,13-dibutyrate-induced vasoconstriction in vivo: characterization of response in genetic hypertension.

To assess the role of protein kinase C (PKC) in the control of vessel tone in vivo in genetic hypertension, the vascular effects of phorbol-12,13-dibutyrate (PDBu), a PKC activator, was measured in the autoperfused hindlimb of reserpinized spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). PDBu infusion (1-3000 ng/kg/min) into the hindlimb elevated perfusion pressure in a dose-related manner. Vasoconstriction response characteristics (latency, T1/2 to peak effect, decay of effect) of PDBu were significantly longer (2- to 10-fold) than that produced by membrane receptor agonists; phenylephrine, SKF 89748, a lipophilic alpha-1 agonist, angiotensin II and 5-hydroxytryptamine.

Chronotropic stimulation: a primary effector for release of atrial natriuretic factor.

Release of atrial natriuretic factor (ANF) following an elevation in heart rate is thought to be mediated primarily by a change in atrial stretch. To evaluate the direct effect of chronotropic stimulation on ANF release, isolated rat left atria were electrically paced (1-9 Hz) at constant resting tension (0.5-4 g), and the amount of immunoreactive ANF (IRANF) released at each frequency and tension was quantitated with a sensitive radioimmunoassay.

Cardiac and noncardiac atrial natriuretic factor (ANF) biosynthesis and storage and plasma ANF in the rat model of chronic ventricular dysfunction.

To evaluate the role of atrial natriuretic factor (ANF) in chronic heart failure (HF), the biosynthesis and storage of ANF in cardiac and noncardiac tissues and the level of plasma ANF were measured in rats exhibiting minimal [2-fold rise in left ventricular end diastolic pressure; myocardial infarct (MI) scar length, 25% left ventricle (LV)] and moderate-severe (3-fold rise in left ventricular end diastolic pressure; decreased contractility (dp/dtmax); MI scar length, 47% LV) chronic HF 30 and 60 days after coronary arterial ligation. In rats with moderate-severe HF (30 days post-MI), the cardiac ANF mRNA concentration (determined by dot blot analysis) increased in three heart chambers [LV, 6-fold; left atria (LA), 3-fold; right ventricle (RV), 2-fold], cardiac immunoreactive ANF (IRANF; determined by RIA) concentration increased on the left side (LV, 7-fold; LA, 33%), but was unchanged (RV) or reduced on the right side (right atria, 33%), and plasma IRANF increased 3-fold above sham control values. Excluding the LV (used for MI scar length), the pattern and magnitude of change in ANF mRNA concentration in moderate-severe HF at 60 days were similar to those at 30 days; the cardiac IRANF concentration at this time was the same (LA) or less than (RV, 66%) sham values, and plasma IRANF increased 6-fold above respective sham values.

Release of atrial natriuretic factor. Effects of repetitive stretch and temperature.

The effect of continuous and repetitive mechanical stretch on release of immunoreactive atrial natriuretic factor (IR-ANF) was studied in isolated rat atria distended by inflation of miniature balloon catheters. After 10 min incubation, the concentration of IR-ANF in the medium increased in proportion to the degree of continuous atrial stretch. Repetitive atrial expansion induced a rate dependent increase in release of IR-ANF which at the highest rate tested (89 inflations/min) was sixfold greater than that observed with continuous maximal expansion.