bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipocalin-Type Prostaglandin D Synthase in Essential Hypertension
Authors: Hirawa Nobuhito , Uehara Yoshio , Yamakado Minoru , Toya Yoshiyuki , Gomi Tomoko , Ikeda Toshio , Eguchi Yutaka , Takagi Masao , Oda Hiroshi , Seiki Kousuke , Urade Yoshihiro , Umemura Satoshi
Published: July 2002

Lipocalin-type prostaglandin D synthase (L-PGDS) reportedly well predicts cardiovascular injuries in humans. However, little is known about the implications of L-PGDS in hypertension. In the present study, we investigated the alterations of serum and urinary L-PGDS in hypertensive patients with or without renal dysfunction. A total of 111 patients with hypertension (EHT; 65 with normoalbuminuria, 23 with microalbuminuria, 12 with macroalbuminuria, 11 with renal failure) and 102 normotensive, nomoalbuminuric subjects (NT) were studied. L-PGDS was measured by enzyme-linked immunosorbent assay, and L-PGDS in the kidney was localized using immunohistochemical methods. Blood pressure was higher in EHT groups than in the NT group (
P
<0.0001). There were no differences in age, gender, BMI, TC, TG, and HbA1c levels among the groups. Serum creatinine and urinary albumin levels were higher in the group with renal failure. Serum levels of L-PGDS were increased in EHT with normoalbuminuria, as compared with NT (0.88±0.05 versus 0.65±0.02 μg/mL;
P
<0.001). Serum levels of L-PGDS increased with the renal function worsened and positively correlated with serum creatinine, particularly in patients with renal impairments (
r
=0.76,
P
<0.0001). Similarly, the urinary L-PGDS excretions in EHT with normoalbuminuria were higher than that in NT (2.31±0.29 versus 1.16±0.14 mg/gCr,
P
<0.001), whereas there were no differences in urinary albumin excretion between the 2 groups. Moreover, urinary L-PGDS excretion increased dramatically with an increase in albuminuria or proteinuria. L-PGDS was stained in the tubules and the interstitium of the kidney in nephrosclerosis. In conclusion, patients with hypertension exhibited a higher level of L-PGDS in serum and urine, and this became increasingly obvious along with advance in renal dysfunction. These data suggest that L-PGDS metabolism is related to blood pressure and kidney injuries associated with hypertension.
Sustained Activation of the Central Baroreceptor Pathway in Angiotensin Hypertension
Authors: Lohmeier Thomas E. , Lohmeier Justin R. , Warren Susan , May Paul J. , Cunningham J. Thomas
Published: July 2002

Recent studies indicate that renal sympathetic nerve activity is chronically suppressed in angiotensin (Ang II) hypertension and that baroreflexes play a critical role in mediating this response. To support these findings, we determined whether the hypertension associated with chronic infusion of Ang II at 4.8 pmol/kg per minute (5ng/kg per minute) produces sustained activation of medullary neurons that participate in the central baroreceptor reflex pathway. We used Fos-like (Fos-Li) protein immunohistochemical methods to determine activation of neurons in the nucleus tractus solitarius (NTS), caudal ventrolateral medulla (CVLM), and rostral ventrolateral medulla (RVLM). Results were compared in three groups of chronically instrumented dogs subjected to infusion of: 1) saline (control); 2) Ang II-2 hours (acute); and 3) Ang II-5 days (chronic). Mean arterial pressure increased 22±3 and 35±3 mm Hg during acute and chronic Ang II infusion, respectively. There was little Fos-Li immunoreactivity in medullary neurons in control dogs. In contrast, during acute Ang II infusion there was a 2- to 3-fold increase in Fos-Li staining in the NTS and CVLM, but no increase in staining in RVLM neurons. As baroreceptor suppression of sympathoexcitatory cells in the RVLM is mediated by activation of neurons in the NTS and CVLM, these results were expected. More importantly, this same pattern of central neuronal activation was observed during chronic Ang II hypertension. Therefore, these results support recent findings indicating that baroreflex suppression of renal sympathetic nerve activity is a long-term compensatory response in Ang II hypertension.
Dipeptidyl Peptidase IV Activity in Patients With ACE-Inhibitor-Associated Angioedema
Authors: Lefebvre Jean , Murphey Laine J. , Hartert Tina V. , Jiao Shan Ru , Simmons William H. , Brown Nancy J.
Published: July 2002

Bradykinin and substance P have been implicated as mediators in angiotensin-converting enzyme inhibitor (ACEI)-associated angioedema. Studies investigating the metabolism of bradykinin in sera from patients with a history of ACEI-associated angioedema and controls suggest that there is a defect in a non-ACE, non-kininase I pathway of bradykinin degradation, such as the aminopeptidase P (APP)/dipeptidyl peptidase IV (DPPIV) pathway. This study tested the hypothesis that serum APP or DPPIV activity is decreased in patients with ACEI-associated angioedema. APP and DPPIV activity were measured in sera collected from patients during ACEI-associated angioedema, from patients with a remote history of ACEI-associated angioedema, and from normotensive and untreated hypertensive controls. The effects of acute and chronic ACEI and corticosteroid treatment on serum DPPIV activity were also assessed. DPPIV activity was similar in normotensive volunteers (37.8±6.3 nmol/mL per min), in untreated hypertensive subjects who had been exposed previously to ACEI without angioedema (36.2±4.3 nmol/mL per min), in hypertensive patients with a remote history of angioedema (35.1±8.5 nmol/mL per min), and in chronically ACEI-treated hypertensive subjects (36.1±5.6 nmol/mL per min). DPPIV activity decreased with increasing age (
R
2
=0.10,
P
=0.016). Subject group significantly affected DPPIV activity (F=6.208,
P
=0.016) such that DPPIV activity was significantly lower in patients with ACEI-associated angioedema (26.9±4.1 nmol/mL per min) than in normotensive controls, in previously ACEI-exposed untreated hypertensive volunteers, or in ACEI-treated hypertensive volunteers, even after controlling for age. There was no effect of acute ACE inhibition or corticosteroids on DPPIV activity. With respect to APP activity, there was no difference between groups. These results suggest that DPPIV activity is depressed in individuals with hypertension during acute ACEI-associated angioedema.
Stimulation of Collagen Production by Transforming Growth Factor-β
1
During Differentiation of Cardiac Fibroblasts to Myofibroblasts
Authors: Petrov Victor V. , Fagard Robert H. , Lijnen Paul J.
Published: July 2002

The aim of the present study was to elucidate how transforming growth factor-β
1
(TGF-β
1
) can stimulate collagen deposition in cardiac tissue by interstitial cells via stimulation of fibroblasts, via myofibroblasts, or via differentiation of fibroblasts to myofibroblasts. The dose- and time-dependent stimulation of collagen production and of expression of α-smooth muscle actin (α-SMA), a marker of myofibroblasts, was studied in cultures of second-passage adult rat cardiac fibroblasts. The TGF-β
1
-stimulated collagen production is positively correlated (
r
=0.68,
P
<0.001) with the appearance of α-SMA. Only at high concentrations (40 to 600 pmol/L) and after a long time (24 to 48 hours) of incubation, TGF-β
1
increases the collagen production and stimulates the differentiation of fibroblasts to myofibroblasts. The maximal stimulation of the collagen production (2-fold,
P
<0.001) observed after incubation of cultures of fibroblasts with 600 pmol/L TGF-β
1
for 48 hours is accompanied by a maximal stimulation of α-SMA expression (3.5-fold,
P
<0.001), when cultures consist mainly of myofibroblasts. The stimulation of collagen production cannot be reversed either after additional incubation of TGF-β
1
-stimulated second-passage cultures for 2 days or in their offspring in the next third passage after incubation for 7 days without TGF-β
1
. The increased collagen production in these third-passage cultures cannot be further stimulated by TGF-β
1
. Our data suggest that TGF-β
1
-stimulated collagen production in cultures of adult rat cardiac ventricular fibroblasts cannot be explained by a direct stimulation of the collagen production either in fibroblasts or in myofibroblasts. Instead, TGF-β
1
induces the differentiation of fibroblasts to myofibroblasts, which have a higher activity for collagen production than fibroblasts.
Fibrosis, Matrix Metalloproteinases, and Inflammation in the Heart of DOCA-Salt Hypertensive Rats: Role of ET
A
Receptors
Authors: Ammarguellat Fatima Z. , Gannon Philippe O. , Amiri Farhad , Schiffrin Ernesto L.
Published: July 2002

In deoxycorticosterone acetate (DOCA)-salt hypertension, the endothelin-1 system is activated and plays a role in cardiac fibrosis. Remodeling of extracellular matrix (ECM) may lead to interstitial fibrosis, which may contribute to heart failure. Imbalance in synthesis and degradation of the ECM by matrix metalloproteinases (MMPs) as well as inflammation may play a role in matrix protein deposition and cardiac remodeling in hypertension. We measured expression of the extracellular matrix protein fibronectin, the activity of the gelatinases MMP-2 and MMP-9, the proinflammatory transcription factor NFκB, and the adhesion molecules, vascular cell adhesion molecule (VCAM)-1 and platelet-endothelial cell adhesion molecule (PECAM)-1 in hearts of DOCA-salt hypertensive (DS) rats treated or not with the endothelin ET
A
antagonist BMS 182874 (BMS). Unilaterally nephrectomized rats (UniNx) were compared with DS rats treated or not with BMS 40 mg/kg/d. Fibronectin deposition was detectable at the first week, and remained elevated thereafter. This increase was abrogated by administration of the ET
A
antagonist. Enzymatic activity of gelatinases was increased (
P
<0.01) in DS compared with control during the first and second week. BMS blocked the increase of MMP-2 and MMP-9 activity at week 1 (
P
<0.05); MMP activity remained lower than in DS at week 2. NF-κB binding activity in DS was higher (
P
<0.05) than it was in controls during the second week, and was reduced by BMS. The adhesion molecules VCAM-1 and PECAM-1, and the antiapoptotic molecule xIAP were upregulated in the left ventricle of the heart of DS rats and downregulated in the rats treated with the ET
A
antagonist. In conclusion, cardiac extracellular remodeling in rats with endothelin-dependent hypertension was associated with increased fibronectin, MMP activity, and upregulation of inflammatory mediators, all of which were reduced by ET
A
antagonism.
Increased Dietary Salt Activates Rat Aortic Endothelium
Authors: Ying Wei-Zhong , Sanders Paul W.
Published: July 2002

The function of vascular endothelium as a biomechanical sensor permits alterations in gene expression in the vascular tree in response to wall stress. The present study explored the mechanism by which the arterial endothelium responds to changes in dietary salt. Normotensive rats were fed diets containing varying amounts of NaCl for 4 days. At that time, levels of phosphorylated p38 MAP kinase, p42/44 MAP kinase, and p46/54 JNK/SAP kinase increased when the diet contained ≥3.0% NaCl. Kinase assays demonstrated dose-response relationships between dietary salt intake and the activities of p38 MAP kinase and p42/44 MAP kinase. Aortic segments from animals on the 8.0% NaCl diet produced greater amounts of total and active transforming growth factor-beta 1 (TGF-β1) and nitric oxide. The MEK1 inhibitor, PD-098059, and the p38 MAP kinase inhibitor, SB-203580, decreased production of these bioactive compounds to background levels. Intravenous injection of tetraethylammonium chloride (TEA) into rats on the 8.0% NaCl diet decreased the activities of p38 MAP kinase and p42/44 MAP kinase, compared with rats on the same diet and given vehicle intravenously. These findings provided direct evidence that dietary salt modulated gene expression in the arterial wall through a tetraethylammonium-sensitive mechanism and activation of the p38 and p42/44 MAP kinase pathways.
Low-Renin Hypertension, Altered Sodium Homeostasis, and an α-Adducin Polymorphism
Authors: Grant Frederick D. , Romero Jose R. , Jeunemaitre Xavier , Hunt Steven C. , Hopkins Paul N. , Hollenberg Norman H. , Williams Gordon H.
Published: July 2002

Defining the genetic basis of common forms of human essential hypertension is most informative when correlated with physiological mechanisms that underlie blood pressure regulation. A polymorphism of the alpha-adducin gene as been associated with elevated blood pressure in the rat, but previous studies of the 460Trp polymorphism of the human alpha-adducin gene have not clearly identified an association with hypertension. In this study, the frequency of the 460Trp allele was 19% and 9 of 279 subjects (3.2%) were homozygous for the 460Trp allele. The systolic blood pressure response to changes in dietary sodium was significantly greater in subjects homozygous for the 460Trp allele (25±4 mm Hg) compared with subjects heterozygous for 460Trp (12±2 mm Hg) or homozygous for the 460Gly allele (14±1 mm Hg). Intracellular erythrocyte sodium content, sodium-lithium countertransport, and renal fractional excretion of sodium were significantly decreased in subjects homozygous for the 460Trp polymorphism (
P
<0.05). There was a significant association between homozygosity for the 460Trp allele and low-renin hypertension. Subjects heterozygous for the 460Trp allele did not have increased salt-sensitivity or an increased frequency of low-renin hypertension. Therefore, this study demonstrates a common genetic basis for altered cellular sodium homeostasis, impaired renal sodium handling, and salt-sensitivity of systolic blood pressure in individuals homozygous for the 460Trp polymorphism of the alpha-adducin gene. Homozygosity for this alpha-adducin allele may be an important determinant for approximately 10% of individuals with low-renin hypertension.
Low-Salt Diet Enhances Vascular Reactivity and Ca
2+
Entry in Pregnant Rats With Normal and Reduced Uterine Perfusion Pressure
Authors: Giardina Jena B. , Cockrell Kathy L. , Granger Joey P. , Khalil Raouf A.
Published: July 2002

Salt moderation is often recommended to prevent excessive increases in blood pressure during pregnancy, particularly in women who are prone to pregnancy-induced hypertension; however, the vascular effects of low dietary salt intake during pregnancy are unclear. We investigated whether a low-salt diet during pregnancy alters the mechanisms of vascular smooth muscle contraction. Active stress and
45
Ca
2+
influx were measured in endothelium-denuded aortic strips of virgin and normal pregnant Sprague-Dawley rats and a hypertensive pregnant rat model produced by reduction in uterine perfusion pressure (RUPP), fed either a normal-sodium (NS, 1% NaCl) or low-sodium diet (LS, 0.2% NaCl) for 7 days. The mean arterial pressure was as follows: virgin/NS 108±8, virgin/LS 117±7, pregnant/NS 102±3, pregnant/LS 117±4, RUPP/NS 119±3, and RUPP/LS 133±6 mm Hg. Phenylephrine (Phe) caused concentration-dependent increases in active stress and
45
Ca
2+
influx that were greater in RUPP rats than in normal pregnant or virgin rats and were enhanced in pregnant/LS and RUPP/LS compared with pregnant/NS and RUPP/NS, respectively. High KCl (16 to 96 mmol/L), which stimulates Ca
2+
entry from the extracellular space, also caused increases in active stress that were greater in RUPP than in normal pregnant, in pregnant/LS than in pregnant/NS, and in RUPP/LS than in RUPP/NS rats. The Phe-induced
45
Ca
2+
influx–active stress relation was greater in RUPP/NS than in pregnant/NS and was enhanced in pregnant/LS and RUPP/LS compared with pregnant/NS and RUPP/NS, respectively. In Ca
2+
-free (2 mmol/L ethylene glycol bis(β-aminoethylether)-N,N,N′,N′-tetra-acetic acid) Krebs, stimulation of intracellular Ca
2+
release by Phe (10
−5
mol/L) or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rats. Thus, a low-salt diet in pregnant and RUPP rats is associated with increases in vascular reactivity that involves Ca
2+
entry from the extracellular space but not Ca
2+
release from the intracellular stores. The enhancement of the Phe-induced Ca
2+
influx–active stress relation in pregnant and RUPP rats on a low-salt diet suggests activation of other vascular contraction mechanisms in addition to Ca
2+
entry. Although it is difficult to extrapolate the experimental data in rats to clinical data in women, the increased vascular reactivity and Ca
2+
entry and the possible enhancement of additional vascular contraction mechanisms with a low-salt diet suggest that reduction of dietary salt intake should be carefully monitored during pregnancy and pregnancy-induced hypertension.
Lysophosphatidylcholine Inhibits Insulin-Induced Akt Activation Through Protein Kinase C-α in Vascular Smooth Muscle Cells
Authors: Motley Evangeline D. , Kabir Syeda M. , Gardner Carla D. , Eguchi Kunie , Frank Gerald D. , Kuroki Toshio , Ohba Motoi , Yamakawa Tadashi , Eguchi Satoru
Published: July 2002

Abstract—

To better understand the intracellular signaling mechanism that causes the association of insulin resistance and hyperlipidemia with cardiovascular diseases, we specifically looked at the ability of lysophosphatidylcholine (lysoPC) to inhibit the Akt activation induced by insulin in cultured rat aortic vascular smooth muscle cells. LysoPC inhibited the insulin-induced phosphorylation of Akt at Ser473, and the inhibition was concentration dependent. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, inhibited the insulin-induced phosphorylation of Akt. LysoPC stimulated PKC phosphorylation at Ser660, which was inhibited by the PKC inhibitor GF109203X. The PKC-α/β-selective inhibitor Go6976 also blocked the PMA- and lysoPC-induced inhibition of Akt phosphorylation by insulin. PKC-α, but not PKC-β, is expressed in vascular smooth muscle cells, and overexpression of PKC-α, but not PKC-β or PKC-δ, inhibited insulin-induced Akt activation. LysoPC rapidly stimulated PKC-α translocation to the membrane. In contrast, pretreatment with the p42/44 mitogen-activated protein kinase kinase inhibitor PD98059 or the p38 mitogen-activated protein kinase inhibitor SB203580 did not block the lysoPC-induced inhibition of Akt phosphorylation by insulin. In addition, lysoPC inhibited the insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 but not that of the insulin receptor β subunit or insulin binding. PMA treatment or PKC-α overexpression also inhibited the tyrosine phosphorylation of IRS-1. From these data, we conclude that lysoPC negatively regulates the insulin signal at the point of IRS-1 through PKC-α in the vasculature, which may explain the association of hyperlipidemia with hyperinsulinemia in cardiovascular diseases.
Increased Angiotensin II-Mediated Src Signaling via Epidermal Growth Factor Receptor Transactivation Is Associated With Decreased C-Terminal Src Kinase Activity in Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats
Authors: Touyz Rhian M. , Wu Xiao-Hua , He Gang , Salomon Steven , Schiffrin Ernesto L.
Published: July 2002

We investigated whether upregulation of Src by Ang II leads to increased extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and whether these processes are associated with altered activation of C-terminal Src kinase (Csk), a negative regulator of Src. Furthermore, the role of epidermal growth factor receptor (EGFR) transactivation by angiotensin II (Ang II) was determined. Ang II-mediated c-Src phosphorylation was significantly greater (≈4-fold,
P
<0.01) in SHR than in Wistar-Kyoto rats (WKY). Ang II increased Csk phosphorylation 2-to 3-fold in WKY but not in SHR. Treatment of the cells with AG1478, a selective EGFR tyrosine kinase inhibitor, decreased Ang II-mediated c-Src phosphorylation, particularly in SHR. Phosphorylation of cortactin and Pyk2/focal adhesion kinase, Src-specific substrates, was increased by Ang II >3-fold, with significantly greater responses in SHR than in WKY (
P
<0.05). Ang II-induced ERK1/2 activation was significantly augmented (
P
<0.05) and sustained in VSMCs from SHR. PP2, a selective Src inhibitor, attenuated these effects and normalized the responses in SHR. Irbesartan, a selective Ang II type 1 receptor blocker, but not PD123319, a selective Ang II type 2 receptor blocker, inhibited Ang II actions. Our results demonstrate that c-Src phosphorylation and Src-dependent ERK1/2 signaling by Ang II are increased in VSMCs from SHR. These processes are associated with blunted Ang II-induced phosphorylation of Csk. EGFR transactivation contributes to Ang II-mediated Src-dependent ERK1/2 signaling. In conclusion, altered regulation of Ang II type 1 receptor-activated c-Src by Csk may be an important upstream modulator of abnormal ERK1/2 signaling in VSMCs from SHR.
Posttranscriptional Control of BNP Gene Expression in Angiotensin II–Induced Hypertension
Authors: Suo Maria , Hautala Nina , Földes Gábor , Szokodi István , Tóth Miklós , Leskinen Hanna , Uusimaa Paavo , Vuolteenaho Olli , Nemer Mona , Ruskoaho Heikki
Published: July 2002

B-type natriuretic peptide (BNP) plasma concentrations are raised in patients with heart failure. In several experimental models of cardiac overload, however, BNP mRNA and plasma BNP peptide levels are normal, despite the persistent increase in blood pressure and ventricular hypertrophy. In this study, the role of transcriptional mechanisms in the regulation of BNP gene expression were studied in angiotensin (Ang) II–induced hypertension by injecting DNA constructs containing the BNP promoter (−2200 to 75 bp of the transcriptional start site) linked to luciferase reporter into rat myocardium. Ang II was administered to conscious rats via intravenous infusion for 2 hours or by subcutaneous minipumps for 6 hours, 12 hours, 3 days, 1 week, and 2 weeks. Ang II increased blood pressure and cardiac mass and induced changes in diastolic function. The left ventricular BNP mRNA levels increased 2.2-fold (
P
<0.001) at 2 hours and peaked at 12 hours (5.2-fold,
P
<0.001). Thereafter, BNP mRNA levels decreased (1.8-fold induction at 3 days,
P
<0.05) and returned to control levels at 1 week, despite persistent hypertension and myocardial hypertrophy. Left ventricular BNP peptide concentrations followed the changes in BNP mRNA levels. The BNP promoter was activated 2.7-fold (
P
<0.05) at 2 hours and remained upregulated up to 2 weeks (2.8-fold,
P
<0.05) during Ang II infusion, except at 12 hours. These results indicate that posttranscriptional control plays a major role in the regulation of ventricular BNP gene expression in Ang II–induced hypertension.
Smoking Impairs Bradykinin-Stimulated t-PA Release
Authors: Pretorius Mias , Rosenbaum David A. , Lefebvre Jean , Vaughan Douglas E. , Brown Nancy J.
Published: July 2002

Bradykinin stimulates tissue plasminogen activator release from human endothelium through a flow-independent, B
2
receptor–dependent mechanism. The present study tests the hypothesis that smoking impairs bradykinin-stimulated tissue plasminogen activator release. Graded doses of nitroprusside (1.6 to 6.4 μg/min), methacholine (3.2 to 12.8 μg/min), and bradykinin (100 to 400 ng/min) were infused in the brachial artery in random order in 20 smokers and 12 nonsmokers matched for age, gender, and body mass index. Forearm blood flow was measured by strain-gauge plethysmography. All 3 drugs caused a dose-dependent increase in forearm blood flow, with no significant difference between smokers and nonsmokers. Bradykinin (
P
=0.001) and methacholine (
P
=0.001) caused significant dose-dependent increases in net tissue plasminogen activator release. The tissue plasminogen activator response to bradykinin was significantly greater than the tissue plasminogen activator response to methacholine in the nonsmokers (maximal net tissue plasminogen activator release, 73.2±21.5 versus 27.6±7.2 ng/min per 100 mL;
P
=0.001) but not in the smokers (maximal net tissue plasminogen activator release, 44.5±10.7 versus 24.8±9.3 ng/min per 100 mL;
P
=0.154). The effect of bradykinin (
P
=0.037), but not methacholine (
P
=0.978), on net tissue plasminogen activator release was significantly reduced in smokers compared with nonsmokers. The vascular tissue plasminogen activator response to bradykinin, but not methacholine, is impaired in smokers. Stimulated tissue plasminogen activator release may be a more sensitive measure of endothelial function than vasodilation.
Trade, Democracy, and the Size of the Public Sector: The Political Underpinnings of Openness
Authors: Adserà Alícia , Boix Carles
Published: July 2002

Politics remains prominently absent in the literature showing that higher levels of trade integration lead to a larger public sector. As openness increases, the state, acting as a social planner, adopts a salient role to minimize the risks of economic integration and secure social peace. Given the highly redistributive nature of both trade and fiscal policies, we claim, however, that the interaction of the international economy and domestic politics leads to three distinct political-economic equilibria. First, nations may embrace protectionist policies to shore up the welfare of key domestic sectors—without engaging, therefore, in substantial public spending. Second, to maintain trade openness in democracies, policymakers develop compensation policies to muster the support of the losers of openness. Finally, given the tax burden of public compensation, pro-free trade sectors may impose an authoritarian regime to exclude (instead of buying off) their opponents. After formally stating the conditions under which each regime emerges, we test the model on a panel data of around sixty-five developing and developed nations in the period 1950–1990 and explore its implications through a set of key historical cases drawn from the last two centuries.
Globalization and the Decline of the Welfare State in Less-Developed Countries
Authors: Rudra Nita
Published: July 2002

Why have trends in government welfare spending in developing countries diverged from those in developed countries? I address this question by investigating the effects of capital and trade flows on government welfare spending in fifty-three developing countries. Using an original measure of labor power in developing countries, I test the links between international markets, labor's political strength, and the welfare state. I argue that labor's collective-action problems, caused by large populations of low-skilled and surplus workers, offset labor's potential political gains from globalization. I show that when the proportion of low-skilled workers in a nation is high, globalization will lead to a decline in welfare spending. Most significantly, the results suggest that in nations where labor-market institutions are not yet well developed, government social-welfare spending is constrained by international market, forces.
New England's First Depression: Beyond an Export-Led Interpretation
Authors: McWilliams James E.
Published: July 2002

Historians of New England's economy traditionally explain the region's recovery from its first depression, which lasted from the early to the mid-1640s, by Massachusetts' export of surplus goods to transatlantic markets (primarily in the West Indies). This conventional interpretation, however, overlooks the timing of the sugar transition in the West Indies as well as the inability of the Bay Colony's local infrastructure at that point to sustain an export trade of the requisite magnitude. The local economy, rather than an export market, was the likely engine of recovery.
Visualizing the Neural Bases of a Disconnection Syndrome with Diffusion Tensor Imaging
Authors: Molko N. , Cohen L. , Mangin J. F. , Chochon F. , Lehéricy S. , Bihan D. Le , Dehaene S.
Published: July 2002

Disconnection syndromes are often conceptualized exclusively within cognitive box-and-arrow diagrams unrelated to brain anatomy. In a patient with alexia in his left visual field resulting from a posterior callosal lesion, we illustrate how diffusion tensor imaging can reveal the anatomical bases of a disconnection syndrome by tracking the degeneration of neural pathways and relating it to impaired fMRI activations and behavior. Compared to controls, an abnormal pattern of brain activity was observed in the patient during word reading, with a lack of activation of the left visual word form area (VWFA) by left-hemifield words. Statistical analyses of diffusion images revealed a damaged fiber tract linking the left ventral occipito-temporal region to its right homolog across the lesioned area of corpus callosum and stopping close to the areas found active in fMRI. The behavioral disconnection syndrome could, thus, be related functionally to abnormal fMRI activations and anatomically to the absence of a connection between those activations. The present approach, based on the “negative tracking” of degenerated bundles, provides new perspectives on the understanding of human brain connections and disconnections.
Representation and Extrapolation in Multilayer Perceptrons
Authors: Browne Antony
Published: July 2002

To give an adequate explanation of cognition and perform certain practical tasks, connectionist systems must be able to extrapolate. This work explores the relationship between input representation and extrapolation, using simulations of multilayer perceptrons trained to model the identity function. It has been discovered that representation has a marked effect on extrapolation.
Virtual Environments for Assessing and Rehabilitating Cognitive/Functional Performance A Review of Projects at the USC Integrated Media Systems Center
Authors: Rizzo Albert A. , Buckwalter J. Galen , McGee Jocelyn S. , Bowerly Todd , Zaag Cheryl van der , Neumann Ulrich , Thiebaux Marcus , Kim Laehyun , Pair Jarrell , Chua Clint
Published: July 2002

Virtual reality (VR) technology offers new options for the creation of sophisticated tools that could be applied in the areas of assessment and rehabilitation of cognitive and functional processes. VR systems allow for the precise presentation and control of dynamic, multisensory, three-dimensional (3-D) stimulus environments, as well as the recording of all behavioral responses that occur within them. Assessment and rehabilitation scenarios that would be difficult if not impossible to deliver using conventional neuropsychological methods are now being developed that take advantage of these VR assets. If empirical studies demonstrate effectiveness, virtual environments (VEs) could be of considerable value for better understanding, measuring, and treating persons with impairments due to traumatic brain injury, neurological disorders, and learning disabilities. This article describes the progress of a VR research program at the USC Integrated Media Systems Center and Information Sciences Institute that has developed and investigated the use of a series of VEs designed to target (i) molecular visuospatial skills using a 3-D, projection-based ImmersaDesk system, and (ii) attention (and soon memory and executive functioning) processes within ecologically valid functional scenarios utilizing a head-mounted display (HMD). Results from completed research, rationales and methodology of works in progress, and our plan for future work is presented. Our primary vision has been to develop VR systems that target cognitive processes and functional skills that are of relevance to a wide range of patient populations with central nervous system (CNS) dysfunction, as well as for the assessment of unimpaired performance. We have also sought to select cognitive/functional targets that intuitively appear well matched to the specific assets available with currently available VR technology.
Evolving Neural Networks through Augmenting Topologies
Authors: Stanley Kenneth O. , Miikkulainen Risto
Published: July 2002

An important question in neuroevolution is how to gain an advantage from evolving neural network topologies along with weights. We present a method, NeuroEvolution of Augmenting Topologies (NEAT), which outperforms the best fixed-topology method on a challenging benchmark reinforcement learning task. We claim that the increased efficiency is due to (1) employing a principled method of crossover of different topologies, (2) protecting structural innovation using speciation, and (3) incrementally growing from minimal structure. We test this claim through a series of ablation studies that demonstrate that each component is necessary to the system as a whole and to each other. What results is signicantly faster learning. NEAT is also an important contribution to GAs because it shows how it is possible for evolution to both optimize and complexify solutions simultaneously, offering the possibility of evolving increasingly complex solutions over generations, and strengthening the analogy with biological evolution.
Green Energy or Organic Food?: A Life‐Cycle Assessment Comparing Two Uses of Set‐Aside Land
Authors: van den Broek Richard , Treffers Dirk‐Jan , Meeusen Marieke , van Wijk Ad , Nieuwlaar Evert , Turkenburg Wim
Published: July 2002

Bioenergy has a large worldwide potential in future climate change abatement, although its application may become limited by demands for land for other functions. The aim of this study was to make an environmental assessment of the use of energy crops in the Netherlands in a context that incorporates scarcity of land.

A base case system was defined, consisting of conventional winter wheat production, set‐aside land (1 hectare, together), and the production of coal‐based electricity. Using life‐cycle assessment, we compared this system with (1) a green energy system in which willow is cultivated on the set‐aside land to replace the coal‐based electricity and (2) an organic agriculture system in which the full hectare produces wheat under the Dutch EKO organic agriculture standard. In this way, the functional unit and the amount of land used is the same in each system. The final system comparison was based on normalized scores per environmental theme.

The green energy system scored the best with respect to acidification, climate change, and energy carrier depletion. The organic food system scored best on terrestrial eco‐toxicity and slightly better on the mutually related themes of seawater and seawater sediment eco‐toxicity. The base case system performed slightly better with regard to eutrophication.

Preferences, from an environmental point of view, for one of the systems should be determined by environmental policy priorities and the severity of local environmental problems. The case studied here shows that when climate change, energy carrier depletion, and acidification are the main drivers behind environmental policy, one should focus not on the extensification of agriculture, but rather dedicate more land to energy crops. Extensification of agriculture would be the preferred system when toxicity from pesticides is considered the main problem.
COSTS OF COURT USAGE IN SEVENTEENTH- AND EIGHTEENTH-CENTURY OTTOMAN ANATOLIA: COURT FEES AS RECORDED IN ESTATE INVENTORIES
Authors: Ergene Bogaç
Published: July 2002

This article investigates the costs of court usage in seventeenth- and eighteenth-century Ottoman Anatolia, with the help of the data collected from twenty-five court registers of Çankırı and Kastamonu. It utilizes the information available for the fees charged by the two courts for dividing the estates of deceased among their heirs. The findings of this article indicate not only that the courts charged for specific services substantially more than what was dictated in official price compilations, but also that the amounts that they charged increased significantly during the period of 60 years covered in this essay. Cet article examine les coûts de l'utilisation de tribunal dans Anatolie pendant l'epoque ottomane au dix-septième- et dix-huitième siècles. Ceci est accompli avec l'aide d'information trouvée dans vingt-cinq registres des tribunaux de Çankırı et de Kastamonu. L'article utilise l'information disponible au sujet des honoraires chargés par le deux tribunaux pour diviser les propriétés du décédé parmi ses héritiers. Ces resultats indiquent non seulement que les tribunaux ont chargé pour les services beaucoup plus que ce qui a été dicté dans les compilations officielles des prix, mais aussi que les montants qu'ils ont chargées augmenté considérablement pendant la période de 60 ans discuté dans cet essai.
Characteristics of Juvenile Offenders Admitting to Sexual Activity with Nonhuman Animals
Authors: Jory Brian , Fleming William , Burton David
Published: July 2002

This study compared the family characteristics, victimization histories, and number of perpetration offenses of juvenile offenders who admitted to having had sex with animals to juvenile offenders who did not. The study found that 96% of the juveniles who had engaged in sex with nonhuman animals also admitted to sex offenses against humans and reported more offenses against humans than other sex offenders their same age and race. Those juveniles who had engaged in sex with animals were similar to other sex offenders in that they also came from families with less affirming and more incendiary communication, lower attachment, less adaptability, and less positive environments. Those juveniles who had engaged in sex with animals reported victimization histories with more emotional abuse and neglect and a higher number of victimization events than other offenders. This would seem to indicate that sex with animals may be an important indicator of potential or co-occurring sex offenses against humans and may be a sign of severe family dysfunction and abuse that should be addressed in the arenas of psychological intervention, juvenile justice programs, and public policy.
BEER PRODUCTION BY THROWING BREAD INTO WATER: A NEW INTERPRETATION OF QOH. XI 1-2
Authors: Homan Michael
Published: July 2002

The passage of Qoh. xi 1-2 has traditionally been understood as a call for charity or international trade. However, in the light of the procedure by which beer was made in the ancient Near East, which involved placing bread into water, a more likely interpretation is that Qoheleth is recommending beer production and consumption in perilous times.
A Footnote in the History of Φυσις
Authors: Llewelyn John
Published: July 2002

Based on Merleau-Ponty's description of nature as that on which we ultimately rely, this essay cultivates the thought that this description also fits an idea of God and therefore of Deus sive Natura. Guided by an outline for a phenomenology of climbing, it is argued that what Heidegger calls readiness to hand presupposes readiness-to-foot (Zufussenheit). The latter gives ground for gratitude not only because it gives ground for enjoyment as gratification, but because it also gives ground for joy understood as a grace, grace understood as having its ground in Natura.
Template‐Assisted Growth of CsxFA1‐xPbI3 with Pulsed Laser Deposition for Single Junction Perovskite Solar Cells
Authors: Kralj Suzana , Artuk Kerem , Wieczorek Alexander , Orlov Nikolai , Eftekhari Zeinab , Saive Rebecca , Garnett Erik , Siol Sebastian , Wolff Christian M. , Morales‐Masis Monica
Published: February 2025

Cesium‐formamidinium lead iodide (CsxFA1‐xPbI3) perovskites are a promising methylammonium‐free alternative for efficient single‐junction solar cells. However, they have not been fully explored by vapor‐phase deposition techniques. Herein, a template‐assisted approach is demonstrated for the growth of CsxFA1‐xPbI3 perovskite films using pulsed laser deposition (PLD) from a single‐source target of mixed precursors. Implementing a lead iodide (PbI2) + CsxFA1‐xPbI3 tailored template, phase‐pure CsxFA1‐xPbI3 films with uniform coverage on both planar and textured substrates are achieved. Compositional analysis via X‐ray fluorescence confirms near‐stoichiometric transfer of the inorganic cations (Cs/Pb), with identical Cs0.2FA0.8PbI3 composition and a bandgap of 1.58 eV achieved in templated and non‐templated films. However, the presence of the template proves essential for attaining phase‐pure films in the photoactive cubic (α‐) phase. Proof‐of‐concept solar cells fabricated with templated‐PLD α‐CsxFA1‐xPbI3 achieve an efficiency exceeding 12.9% on 0.1 cm2 area devices without the employment of passivation approaches. Additionally, increasing deposition rates does not alter the phase, morphology, or optoelectronic properties of the templated films on textured substrates, indicating the robustness of this methodology. The compositional control of PLD for Cs‐FA‐based perovskites is showcased, and template‐assisted growth is demonstrated as a reliable pathway to high‐quality reproducible perovskite films.
Dual Interface Passivation With Multi‐Site Regulation Toward Efficient and Stable Inverted Perovskite Solar Cells
Authors: Li Kunpeng , Han Yong , Zhao Xinlong , Wang Tao , Zhou Mengni , Xie Zhewen , Li Zhishan , Zhang Huicong , Li Fashe , Wang Hua , Zhu Xing , Chen Jiangzhao , Zhu Tao
Published: February 2025

The rapid crystallization process of perovskite produces a large number of defects that remain a critical factor that disturbs the performance of perovskite solar cells (PSCs). In this research, these challenges are mitigated by introducing multifunctional 2,6‐pyridinedicarboxylic acid chloride (PAC) as an additive into perovskite. During the thermal annealing process, the predominant accumulation of PAC occurs at the upper and buried interfaces of perovskite film. PAC possesses multiple passivating sites that facilitate the anchoring of lead and iodine defects, thereby enhancing the quality of the perovskite material across both its dual interfaces and grain boundaries. With this unique property, combined with the advantages of enhanced crystallization, reduced non‐radiative recombination, boosted charge carrier mobility, and optimal energy level alignment, the PSC achieved a power conversion efficiency (PCE) of 25.60% and maintained more than 90% efficiency after 3000 h under one solar equivalent light and more than 90% efficiency after 1400 h under dark and high temperature (85 °C). The dual interface passivation strategy provides a sustainable solution to both stability and environmental challenges for the commercialization of perovskite solar cells.
Development of Moringa Protein‐Polysaccharide Complexes for Enhanced Anti‐Scaling Properties in Reverse Osmosis Membranes for Underground Water Desalination
Authors: Al‐Omari Mohammad Hasan , Abu‐Rayyan Ahmed , Ragab Ahmed H. , Taher Mostafa A. , El‐Sayed El‐Sayed M. , Taha A. , Mubarak Mahmoud F.
Published: February 2025

This study introduces a Moringa oleifera protein‐alginate complex (MPAC) as an effective anti‐scaling material for reverse osmosis (RO) desalination of brackish groundwater. Extracted Moringa protein (MP) combined with sodium alginate (Alg) forms stable complexes applied as a thin film on polyamide (PA) RO membranes. Characterization techniques, including FTIR, SEM, TGA, DLS, and XRD, confirmed the structure, morphology, thermal stability, particle size (200–350 nm), zeta potential (−35 to −45 mV), and semi‐crystallinity of the MPAC. Desalination tests showed a significant reduction in scaling 60% for calcium carbonate (CaCO3) and 45% for calcium sulfate (CaSO4) over 72 h, with water flux sustained at 90%–95% and salt rejection above 98%. The MPAC's anti‐scaling performance is due to its chelation of calcium and magnesium ions, forming a barrier that prevents scale nucleation. This sustainable, scalable material improves RO membrane efficiency, with future work planned to optimize its composition for broader desalination applications.
Understanding factors that influence the drug choice of prescribers: A Q‐methodology study
Authors: Hartjes Mariëlle G. , Elsevier Annelot E. F. , Grijpma Jan Willem , Richir Milan C. , van Agtmael Michiel A. , Tichelaar Jelle
Published: February 2025

Introduction

Therapeutic decision‐making often involves weighing several treatment options on the basis of, among other things, the disease profile, patient characteristics but also prescriber‐specific factors. This study investigated the factors influencing therapeutic decision‐making among prescribers and explores how these factors differ between healthcare professionals.

Methods

This Q‐methodology study involved 37 participants from different medical backgrounds, including physicians, dentists, midwives, physician assistants and advanced nurse practitioners from various intra‐ and extramural settings in the Netherlands. Participants ranked 55 factors on their importance for medication prescribing, and factor analysis was used to identify distinct prescriber profiles. These profiles were subsequently enriched using qualitative data derived from post‐sorting interviews.

Results

Four prescriber profiles were identified that explained 59% of the study variance: pragmatic contextual, guideline oriented, experience driven and vulnerability focused. Several factors were ranked differently in each profile. The pragmatic contextual profile emphasized patient context and risk prevention, the guideline‐oriented profile adhered to clinical guidelines, the experience‐driven profile relied on clinical experience and patient‐centred communication, and the vulnerability‐focused profile prioritized personalized care for specific patient groups.

Conclusion

This study sheds light on the diverse factors influencing prescriber decision‐making in medical practice. By identifying four prescriber profiles, it reveals the complexity and diversity in how prescribers balance guidelines, clinical experience and patient‐specific considerations in their practice. These findings offer direction for developing educational and policy initiatives to enhance the quality of prescribing, ultimately improving patient outcomes.
Systematic Investigation of Cu‐ZnO‐MnOX Catalysts for CO2 Hydrogenation to Methanol
Authors: Guo Tuo , Wang Lin , Zhai Dongdong , Yuan Yongning , Guo Qingjie
Published: February 2025

Currently, the doping and modification of Cu‐ZnO catalysts is a research hotspot for CO2 to methanol. In this work, the impact of MnOX additive doping on the catalytic activity of Cu‐ZnO catalysts for CO2 hydrogenation to methanol was systematically examined. A series of ternary Cu‐ZnO‐MnOX catalysts were produced by the co‐precipitation method, and their physicochemical structures and catalytic activities were characterized. MnOX enhanced the dispersion of Cu and Zn species, obtained a stable crystalline phase, and formed a mesoporous structure with a larger specific surface area, which increased the effective contact area of the gas. Moreover, the appropriate amount of MnOX generated more oxygen vacancies and medium‐strong basic sites in the catalyst, which effectively promoted the adsorption and conversion of CO2, and thus improved the methanol yield. The outcomes demonstrated the best activity was achieved when the molar content of MnOX was 10% (CZM‐10), with a methanol time‐space yield (STY) of 233.23 gMeOH/(kgcat·h) at 220 °C. In‐situ DRIFTS show the CO2 methanolization of CZM catalyst via a formate mechanism. This study is important to produce novel catalysts for CO2 hydrogenation to methanol.