Irreversible Feature Research Articles

Doping of large amount tetravalent Ge ions into Fe2O3 structure and experimental results on modified structural, optical and electronic properties

We report the doping of high concentration of tetravalent Ge4+ ions (5 mol % for x = 0.05–30 mol % for x = 0.30) at the Fe3+ sites of Fe2-xGexO3 system by chemical coprecipitation route. The charge state of Fe and Ge ions has been modified into lower values, in addition to their normal +3 and + 4 states, to stabilize the rhombohedral phase of hematite (α-Fe2O3) structure. X-ray photoelectron spectra and optical band gap measurements indicated a combination of ionic and covalence character of metal-oxygen bonds as an effect of Ge doping in the hematite structure. The Ge doped hematite samples have exhibited semiconductor properties with band gap of 1.50–4.70 eV and remarkably enhanced electrical conductivity (σ ∼ 10−4 S/m) in comparison to α-Fe2O3 (10−11 S/m). The results confirmed the strategy of enhancing electrical conductivity in hematite structure by doping of tetravalent cations. The thermo-conductivity measurements using warming and cooling modes showed highly irreversible feature at higher temperatures. Some of the samples indicated metal-like state at lower temperature, in addition to semiconductor state at higher temperatures. It has been understood that combination of ionic and covalence character of the metal-oxygen bonds has played an important role in modifying the semiconductor properties in Ge doped Fe2O3 system.

OTB-morph: One-time Biometrics via Morphing

Cancelable biometrics are a group of techniques to transform the input biometric to an irreversible feature intentionally using a transformation function and usually a key in order to provide security and privacy in biometric recognition systems. This transformation is repeatable enabling subsequent biometric comparisons. This paper introduces a new idea to be exploited as a transformation function for cancelable biometrics aimed at protecting templates against iterative optimization attacks. Our proposed scheme is based on time-varying keys (random biometrics in our case) and morphing transformations. An experimental implementation of the proposed scheme is given for face biometrics. The results confirm that the proposed approach is able to withstand leakage attacks while improving the recognition performance.

S-40-6: ACTIVATION OF CATHEPSIN S/CXCL1 AXIS-MEDIATED MACROPHAGE AND TUBULAR CELL CROSSTALK LEADS TO RENAL INFLAMMATION AND FIBROSIS

Chronic kidney disease (CKD) is a progressive and irreversible pathological feature with no effective therapies in clinic. Persistent inflammation is a key characteristic of CKD that leads to progressive renal fibrosis. Cathepsin S (Cat S) is a cysteine protease contributing to the progression of multiple diseases through modulating inflammation, but its role in the pathogenesis of CKD remains unknown. Here, we found that Cat S was significantly upregulated in renal macrophage during unilateral ureteral obstruction (UUO). Knockout of Cat S attenuated, whereas AAV (adeno-associated virus)-mediated macrophage-specific overexpression of Cat S exacerbated macrophage recruitment, inflammatory factors expression, renal injury and epithelial mesenchymal transition (EMT). Using macrophage depletion, bone marrow transplantation, protein chip and luciferase reporter assays, we determined that macrophage-derived Cat S induced CXCL1 secretion from tubular cells which mediated macrophage recruitment. Immunoprecipitation combined with mass spectrometry identified that Cat S directly bind with Rack1, which disrupted the Rack1-IKK-alpha complex to activate NF-kappaB signaling. Knockdown of CXCL1 attenuated aggravating pathological changes in macrophage-specific overexpression of Cat S mice. Furthermore, therapeutic administration of Cat S inhibitor significantly reversed renal injury in UUO mice. In patients with renal tubulointerstitial lesions, increase expression of plasma and renal Cat S was associated with renal function impairment and fibrosis severity. Our study demonstrated that Cathepsin S/CXCL1 axis mediated interaction between macrophage and tubular cell that contributed to CKD, with translational implications in humans.

Loss of BTK ameliorates the pathological cardiac fibrosis and dysfunction

Cardiac fibrosis is a common irreversible pathological feature of diverse heart disorders. Uncontrolled cardiac fibrosis contributes to maladaptive cardiac remodeling and eventually heart failure. However, the molecular determinants of ischemic and non-ischemic pathological cardiac fibrosis remain largely unknown. Here, we investigated the role of Bruton's tyrosine kinase (BTK) in cardiac fibrosis and remodeling of mice under various pathological conditions. BTK expression was increased in myocardium of mice after pressure overload or myocardial infarction (MI). BTK was mainly located in cardiac fibroblasts of myocardium, and its expression in isolated cardiac fibroblasts was also upregulated following TGF-β treatment. The deficiency or pharmacological inhibition of BTK with the second-generation inhibitor Acalabrutinib attenuated cardiac fibrosis, preserved cardiac function and prevented adverse cardiac remodeling, which protected against heart failure in mice following pressure overload or MI. BTK deficiency or inhibitor treatment significantly decreased the expression of pro-fibrotic molecules in isolated cardiac fibroblasts and inhibited the transition of fibroblasts to myofibroblasts in response to diverse pathological stresses. BTK directly bound and phosphorylated TGF-β receptor Ⅰ (TβRⅠ) at tyrosine 182, and then promoted the activation of downstream SMAD-dependent or -independent TGF-β signaling, leading to the enhanced transition of fibroblasts to pro-fibrotic myofibroblasts and the excessive extracellular matrix gene expression. Our finding uncovers a driving role of BTK in cardiac fibrosis and dysfunction following pressure overload and MI stress, and highlights novel pathogenic mechanisms in ischemic and non-ischemic maladaptive cardiac remodeling, which presents as a promising target for the development of anti-fibrotic therapy.

PGC1α plays a pivotal role in renal fibrosis via regulation of fatty acid metabolism in renal tissue.

Renal fibrosis is a common and irreversible pathological feature of end-stage renal disease caused by multiple etiologies. The role of inflammation in renal fibrosis tissue has been generally accepted. The latest view is that fatty acid metabolism disorder contributes to renal fibrosis. peroxisome proliferator activated receptor-gamma coactivator 1α (PGC1α) plays a key role in fatty acid metabolism, regulating fatty acid uptake and oxidized protein synthesis, preventing the accumulation of lipid in the cytoplasm, and maintaining a dynamic balanced state of intracellular lipid. In multiple animal models of renal fibrosis caused by acute or chronic kidney disease, or even age-related kidney disease, almost all of the kidney specimens show the down-regulation of PGC1α. Upregulation of PGC1α can reduce the degree of renal fibrosis in animal models, and PGC1α knockout animals exhibit severe renal fibrosis. Studies have demonstrated that AMP-activated protein kinase (AMPK), MAPK, Notch, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), epidermal growth factor receptor (EGFR), non-coding RNA (ncRNAs), liver kinase B1 (LKB1), hairy and enhancer of split 1 (Hes1), and other pathways regulate the expression of PGC1α and affect fatty acid metabolism. But some of these pathways interact with each other, and the effect of the integrated pathway on renal fibrosis is not clear.

Smelling multiple sclerosis: Different qualities of olfactory function reflect either inflammatory activity or neurodegeneration

Background: Peripapillary retinal nerve fiber layer (pRNFL) thickness and olfactory function are both emerging biomarkers in multiple sclerosis (MS). Impairment of odor identification and discrimination is an irreversible feature of more advanced MS suggested to be associated with neurodegeneration, while olfactory threshold is a transient feature of early, active MS possibly associated with short-term inflammatory disease activity. Objective: The aim of this study was to validate the association of olfactory (dys)function and parameters of MS disease course in a large cohort of MS patients and to correlate olfactory function with pRNFL thickness as a surrogate biomarker of neurodegeneration. Methods: In a cross-sectional design, olfactory function was assessed using the Sniffin’ Sticks test, which quantifies three different qualities of olfactory function (threshold, discrimination, and identification). pRNFL thickness was measured by spectral-domain optical coherence tomography (OCT). Results were correlated with age, sex, disease duration, relapses, Expanded Disability Status Scale (EDSS), cognitive function, depression, smoking, and pRNFL thickness by multivariable linear regression models. Results: We included 260 MS patients (mean age of 35.9 years, 68.7% female). Olfactory threshold correlated significantly with number of relapses in the year prior to assessment and shorter disease duration. Odor discrimination, identification, and their sum score were significantly correlated with longer disease duration, higher EDSS, and reduced cognitive function. pRNFL thickness was associated with identification and discrimination, but not with threshold. Conclusion: Olfactory threshold is a marker of short-term inflammatory relapse activity unrelated to parameters of neurodegeneration, while odor identification and discrimination are markers of neurodegeneration mostly independent of relapse activity. Assessment of olfactory function provides an opportunity to stratify MS patients with regard to inflammation and neurodegeneration.

Experimental analysis to the structural relaxation of Ti48Zr20V12Cu5Be15 metallic glass matrix composite

The mechanical relaxation characteristics of in-situ Ti48Zr20V12Cu5Be15 metallic glass matrix composite with dendrites reinforced are investigated by using mechanical spectroscopy. An abnormal internal friction behavior below the glass transition temperature is detected. Considering the irreversible feature and based on the transmission electron microscopy analysis, the abnormal internal friction behavior is mainly induced by the precipitation of nanocrystals in the dendritic phase. In order to understand better the dynamic mechanical properties of the Ti48Zr20V12Cu5Be15 metallic glass matrix composite, the kinetic characteristics of glass transition are analyzed in the framework of quasi-point defects theory. In addition, an isothermal annealing conducted at lower than the glass transition temperature induces a significant change on both modulus and loss factor, the kinetics of relaxation under annealing can be well described by the stretched exponential relaxation equation.

Magnetotransport evidence for irreversible spin reorientation in the collinear antiferromagnetic state of underdoped Nd2−xCexCuO4

We make use of the strong spin-charge coupling in the electron-doped cuprate $\mathrm{Nd}_{2-x}\mathrm{Ce}_x\mathrm{CuO}_4$ to probe changes in its spin system via magnetotransport measurements. We present a detailed study of the out-of-plane magnetoresistance in underdoped single crystals of this compound, including the nonsuperconducting, $0.05\,\leq x\,\leq 0.115$, and superconducting, $0.12\,\leq x\,\leq 0.13$, compositions. Special focus is put on the dependence of the magnetoresistance on the field orientation in the plane of the CuO$_2$ layers. In addition to the kink at the field-induced transition between the noncollinear and collinear antiferromagnetic configurations, a sharp irreversible feature is found in the angle-dependent magnetoresistance of all samples in the high-field regime, at field orientations around the Cu--O--Cu direction. The obtained behavior can be explained in terms of field-induced reorientation of Cu$^{2+}$ spins within the collinear antiferromagnetic state. It is, therefore, considered as an unambiguous indication of the long-range magnetic order.

Photochemistry and Anion-Controlled Structure of Fe(III) Complexes with an α-Hydroxy Acid-Containing Tripodal Amine Chelate

The tripodal amine chelate with two pyridyl groups and an α-hydroxy acid (AHA) group, Pyr-TPA-AHA, was synthesized. Different Fe(III) complexes form with this chelate depending upon the counterion of the Fe(III) source used in the synthesis. A dinuclear complex, Fe(III)2(Pyr-TPA-AHA)2(μ-O), 1, and mononuclear complexes Fe(III)(Pyr-TPA-AHA)X (X = Cl- or Br-, 2 and 3, respectively) were synthesized. 2 can be easily converted to 1 by addition of silver nitrate or a large excess of water. The structure of 1 was solved by X-ray crystallography (C32H34N6O7Fe2·13H2O, a = 14.1236(6) Å, b = 14.1236(6) Å, c = 21.7469(15) Å, α = β = γ = 90°, tetragonal, P42212, Z = 4). 2 and 3 each have simple quasireversible cyclic voltammograms with E1/2 (vs aqueous Ag/AgCl) = +135 mV for 2 and +470 for 3 in acetonitrile. The cyclic voltammogram for 1 in acetonitrile has a quasireversible feature at E1/2 = -285 mV and an irreversible cathodic feature at -1140 mV. All three complexes are photochemically active upon irradiation with UV light, resulting in cleavage of the AHA group and reduction of the iron to Fe(II). Photolysis of 1 results in reduction of both Fe(III) ions in the dinuclear complex for each AHA group that is cleaved, while photolysis of 2 and 3 results in reduction of a single Fe(III) for each AHA cleavage. The quantum yields for 2 and 3 are significantly higher than that of 1.

Light-induced self-assembly of active rectification devices.

Self-propelled colloidal objects, such as motile bacteria or synthetic microswimmers, have microscopically irreversible individual dynamics-a feature they share with all living systems. The incoherent behavior of individual swimmers can be harnessed (or "rectified") by microfluidic devices that create systematic motions that are impossible in equilibrium. We present a computational proof-of-concept study showing that such active rectification devices could be created directly from an unstructured "primordial soup" of light-controlled motile particles, solely by using spatially modulated illumination to control their local propulsion speed. Alongside both microscopic irreversibility and speed modulation, our mechanism requires spatial symmetry breaking, such as a chevron light pattern, and strong interactions between particles, such as volume exclusion, which cause a collisional slowdown at high density. Together, we show how these four factors create a novel, many-body rectification mechanism. Our work suggests that standard spatial light modulator technology might allow the programmable, light-induced self-assembly of active rectification devices from an unstructured particle bath.

Profiling the role of mammalian target of rapamycin in the vascular smooth muscle metabolome in pulmonary arterial hypertension.

Increased proliferation and resistance to apoptosis of pulmonary arterial vascular smooth muscle cells (PAVSMCs), coupled with metabolic reprogramming, are key components of pulmonary vascular remodeling, a major and currently irreversible pathophysiological feature of pulmonary arterial hypertension (PAH). We recently reported that activation of mammalian target of rapamycin (mTOR) plays a key role in increased energy generation and maintenance of the proliferative, apoptosis-resistant PAVSMC phenotype in human PAH, but the downstream effects of mTOR activation on PAH PAVSMC metabolism are not clear. Using liquid and gas chromatography-based mass spectrometry, we performed pilot metabolomic profiling of human microvascular PAVSMCs from idiopathic-PAH subjects before and after treatment with the selective adenosine triphosphate-competitive mTOR inhibitor PP242 and from nondiseased lungs. We have shown that PAH PAVSMCs have a distinct metabolomic signature of altered metabolites-components of fatty acid synthesis, deficiency of sugars, amino sugars, and nucleotide sugars-intermediates of protein and lipid glycosylation, and downregulation of key biochemicals involved in glutathione and nicotinamide adenine dinucleotide (NAD) metabolism. We also report that mTOR inhibition attenuated or reversed the majority of the PAH-specific abnormalities in lipogenesis, glycosylation, glutathione, and NAD metabolism without affecting altered polyunsaturated fatty acid metabolism. Collectively, our data demonstrate a critical role of mTOR in major PAH PAVSMC metabolic abnormalities and suggest the existence of de novo lipid synthesis in PAVSMCs in human PAH that may represent a new, important component of disease pathogenesis worthy of future investigation.

Conventional superconductivity and hysteretic Campbell penetration depth in single crystals MgCNi3

Single crystals of MgCNi$_3$, with areas sized up to 1 mm$^{2}$, were grown by the self flux method using a cubic anvil high pressure technique. The first critical field \textit{H$_{c1}$}, determined from a zero temperature extrapolation, is around 18 mT. Using the tunnel - diode resonator technique, the London penetration depth was measured with no applied \textit{dc} field and the Campbell penetration depth was measured with the external \textit{dc} fields up to 9T for two different sample orientations with respect to the direction of applied magnetic field. The absolute value of the London penetration depth, $\lambda(0) = 245 \pm 10$ nm was determined from the thermodynamic Rutgers formula. The superfluid density, $\rho_s=(\lambda(0)/\lambda(T))^2$ was found to follow the clean isotropic \textit{s}-wave behavior predicted by the weak - coupling BCS theory in the whole temperature range. The low - temperature behavior of the London penetration depth fits the BCS analytic form as well and produces close to the weak - coupling value of $\Delta (0)/k_BT_c = 1.71$. The temperature dependence of the upper critical field, \textit{$H_{c2}$}, was found to be isotropic with a slope at \textit{T$_c$} of -2.63 T/K and \textit{H$_{c2}$}(0) $\approx$ 12.3 T at zero temperature. The Campbell penetration depth probes the vortex lattice response in the mixed state and is sensitive to the details of the pinning potential. For MgCNi$_3$, an irreversible feature has been observed in the TDR response when the sample is field-cooled and warmed versus zero-field-cooled and warmed. This feature possesses a non-monotonic field dependence and has commonly been referred to as the peak effect and is most likely related to a field - dependent non - parabolic pinning potential.

MTOR and vascular remodeling in lung diseases: current challenges and therapeutic prospects

Mammalian target of rapamycin (mTOR) is a major regulator of cellular metabolism, proliferation, and survival that is implicated in various proliferative and metabolic diseases, including obesity, type 2 diabetes, hamartoma syndromes, and cancer. Emerging evidence suggests a potential critical role of mTOR signaling in pulmonary vascular remodeling. Remodeling of small pulmonary arteries due to increased proliferation, resistance to apoptosis, and altered metabolism of cells forming the pulmonary vascular wall is a key currently irreversible pathological feature of pulmonary hypertension, a progressive pulmonary vascular disorder with high morbidity and mortality. In addition to rare familial and idiopathic forms, pulmonary hypertension is also a life-threatening complication of several lung diseases associated with hypoxia. This review aims to summarize our current knowledge and recent advances in understanding the role of the mTOR pathway in pulmonary vascular remodeling, with a specific focus on the hypoxia component, a confirmed shared trigger of pulmonary hypertension in lung diseases. We also discuss the emerging role of mTOR as a promising therapeutic target and mTOR inhibitors as potential pharmacological approaches to treat pulmonary vascular remodeling in pulmonary hypertension.

Synthesis and structural characterisation of (aryl-BIAN)copper(i) complexes and their application as catalysts for the cycloaddition of azides and alkynes

A series of Ar-BIAN-based copper(I) complexes (where Ar-BIAN = bis(aryl)acenaphthenequinonediimine) were synthesised and characterised by (1)H and (13)C NMR spectroscopies, FT-IR spectroscopy, MALDI-TOF-MS spectrometry, cyclic voltammetry and single crystal X-ray diffraction. The bis-chelated complexes of general formula [Cu(Ar-BIAN)(2)]BF(4) (where Ar = C(6)H(5) (1), 4-iPrC(6)H(4) (3), 2-iPrC(6)H(4) (4)) were prepared by reaction of [Cu(NCMe)(4)]BF(4) with two equivalents of the corresponding Ar-BIAN ligands, in dichloromethane, while the mono-chelated complexes of the type [Cu(Ar-BIAN)L(2)]BF(4) (where Ar = 2,6-iPr(2)C(6)H(3), L = PhCN (6); Ar = 4-iPrC(6)H(4), L = PPh(3) (7)) were readily accessible by treatment of [Cu(NCR)(4)]BF(4) (R = Me, Ph) with one equivalent of the corresponding Ar-BIAN ligands in the absence or presence of two equivalents of PPh(3), in the same solvent. The structures of complexes 3, 4, 6 and 7 were obtained by single crystal X-ray diffraction, showing distorted tetrahedral geometries around the copper centres in all cases. The electrochemical studies of these complexes and of the already reported [Cu(2,4,6-Me(3)C(6)H(2)-BIAN)(2)]BF(4) (2) and [Cu(2,6-iPr(2)C(6)H(3)-BIAN)(NCMe)(2)] (5), demonstrated that the bis-chelated complexes 1-4 undergo a reversible one-electron reduction or oxidation processes on copper, while the mono-chelated complexes 5-7 show a partially reversible oxidation and an irreversible reduction feature. Both kinds of (Ar-BIAN)copper(I) complexes are active catalysts for the copper(I)-catalysed azide-alkyne cycloaddition reaction (CuAAC). Complex 7, bearing PPh(3) ligands, exhibits the highest catalytic activity, which is comparable with that of the typical CuSO(4)-sodium ascorbate catalyst system.

Electrochemically induced oxidative cyclization of 2,3‐dihydroxypyridine. Synthesis of a novel highly oxygenated heterocyclic compound

Electrochemical oxidation of 2,3‐dihydroxypyridine in aqueous phosphate buffer solution at a glassy carbon electrode has been studied using cyclic voltammetry and controlled potential coulometry. The results indicate that oxidation of 2,3‐dihydroxypyridine on glassy carbon electrode shows an irreversible feature in aqueous solution. This data indicates that the electrochemically generated pyridindione is unstable and via an oxidative conversion pathway converts to a novel highly oxygenated heterocyclic compound. By means of the obtained electrochemical data, an efficient, one‐pot method for the synthesis of this heterocyclic compound based on the oxidative cyclization of 2,3‐dihydroxypyridine under green conditions, and in a good yield and purity is described. Copyright © 2011 John Wiley & Sons, Ltd.

Telomere length of subcutaneous adipose tissue cells is shorter in obese and formerly obese subjects

Obesity and increased fat mass are associated with increased adipocyte proliferation. Telomere length can serve as a biomarker of a cell's biological (vs chronological) age. To gain insight in the physiology of adipose tissue, we aimed to investigate telomere length in subcutaneous adipose tissue in relation to age and obesity. Telomere length was measured in 72 subcutaneous adipose tissue samples from 21 nonobese and 51 obese subjects. Telomere length of subcutaneous adipose tissue cells was negatively associated with body mass index (BMI), systolic blood pressure and fasting triglycerides. After controlling for age, fasting glucose, triglycerides and smoking status, BMI (P=0.009) contributed independently to 16% of telomere length variance. Interestingly, formerly obese patients (n=10) had shorter telomere length than never-obese subjects (n=12) of similar age, sex and BMI (7.1+/-1.3 vs 9.08+/-1.8 kb, P=0.01). In summary, adipose tissue cells from obese subjects show a shorter telomere length. The shorter telomere length of formerly obese subjects suggests that this is an established, irreversible feature of obesity that could contribute to its comorbidities.

Reproductive success and pollen dispersal in urban populations of an insect-pollinated hay-meadow herb

Abstract Urban development increasingly occupies more landscape and is responsible for habitat alteration and fragmentation of so many ecosystems that urban environments can no longer be excluded from the areas to be considered in conservation strategies. Appropriate management measures ensuring population viability are needed, but due to the usually irreversible feature of the urbanisation process, the measures may differ from non-urbanised areas. Sufficient gene flow levels, leading to successful seed production, appear to be a key element in the sustainable persistence of insect-pollinated plant remnant populations. This study investigated reproductive success and pollen dispersal patterns in Centaurea jacea , an insect-pollinated hay-meadow herb, in the Brussels urban area (Belgium). Reproductive performance of urban park populations was compared with populations occurring in urban semi-natural sites. Pollen dispersal patterns were examined within and among-population patches from two urban parks using fluorescent dye as a pollen analogue. Urban park populations showed a higher reproductive success than those in urban semi-natural sites. Depositions of fluorescent dye particles on recipient individuals were found within populations (

Drugs with Blocking Effects on the Renin–Angiotensin–Aldosterone System Do Not Improve Endothelial Dysfunction Long-Term in Hypertensive Patients

In essential hypertension, endothelial dysfunction has been documented many times and correlates with prognosis. The influence of the renin-angiotensin-aldosterone system (RAAS) on endothelial dysfunction has also been studied. The present study investigated the duration of the effects of RAAS-blocking drugs on endothelial function in 44 consecutive, never-treated, outpatients with mild to moderate hypertension. Patients (11 per group) received an angiotensin receptor blocker (ARB; irbesartan 300 mg/day or valsartan 160 mg/day) or an angiotensin-converting enzyme inhibitor (ACEi; fosinopril 10 mg/day or quinapril 20 mg/day). If target blood pressure (< 140/90 mmHg) was not achieved, 12.5 mg/day hydrochlorothiazide was added. Endothelial function, assessed by measuring brachial artery diameter, did not change significantly after 6 weeks, 1 year or 3 years of treatment in any group. Across all groups, endothelium-dependent and -independent vasodilation increased significantly after 6 weeks but, after 1 year, decreased below baseline and was at a similar level after 3 years; groups did not differ significantly. Both ACEi and ARB had similar effects on endothelial function; improvement occurred at the start of treatment but was not maintained. Endothelial dysfunction may be a resistant or irreversible feature of hypertension, requiring high doses of antihypertensive drugs and above-average patient compliance.

Vortex State Microwave Resistivity in Tl-2212 Thin Films

We present measurements of the field induced changes in the 47 GHz complex resistivity, Δρ~(H, T), in Tl2Ba2CaCu2O8+x (TBCCO) thin films with T c ≃ 105 K, prepared on CeO2 buffered sapphire substrates. At low fields (μ0 H < 10 mT) a very small irreversible feature is present, suggesting a little role of intergranular phenomena. Above that level Δρ~(H, T exhibits a superlinear dependence with the field, as opposed to the expected (at high frequencies) quasilinear behaviour. We observe a crossover between predominantly imaginary to predominantly real (dissipative) response with increasing temperature and/or field. In addition, we find the clear scaling property Δρ~(H, T = Δρ~[H/H * (T)], where the scaling field H ∗ (T) maps closely the melting field measured in single crystals. We discuss our microwave results in terms of loss of flux lines rigidity.

2-(1-adamantyl)-4-(thio)chromenone-6-carboxylic acids: potent reversible inhibitors of human steroid sulfatase.

Steroid sulfatase (STS) is an attractive target for the potential therapy of a number of estrogen- and androgen-dependent disorders. Most potent STS inhibitors known so far act as irreversible enzyme blockers and feature an aryl sulfamate moiety; even minor modifications at the sulfamate group result in drastically decreased activity. On the basis of a recently reported subclass of highly potent STS inhibitors, i.e., chromenone sulfamates, we now extended the investigation of structure-activity relationships to hitherto unstudied sulfamate replacements. Thereby, we discovered 2-(1-adamantyl)-4-(thio)chromenone-6-carboxylic acids (5d and 5j) as potent, reversible inhibitors of STS. In a cell-free system using purified human STS, both new inhibitors show similar Ki values (0.50 microM and 0.53 microM, respectively). However, the thio analogue 5j is superior to 5d (IC50 = 0.18 microM versus 9.4 microM) in a cellular assay system using CHO cells overexpressing STS. Compound 5j is an example of a reversible STS inhibitor with potent activity toward the target enzyme in a cellular test system. Moreover, 5d,j are stable and have no estrogenic potential.