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PubMed1999

Correlation of CD44S expression in renal clear cell carcinomas with subsequent tumor progression or recurrence.

BACKGROUND: Recent reports have shown altered expression of CD44 in renal cell carcinomas. However, to the authors' knowledge there are no data correlating CD44 expression in renal cell carcinomas with subsequent tumor progression or recurrence, nor is there information about the presence of particular splice variants of CD44 in these tumors. METHODS: The authors examined the immunohistochemical expression of CD44S, the standard isoform of CD44, in renal cell carcinomas from 43 patients using 2 different monoclonal antibodies, Mab2137 and Hermes-3. In addition, they stained the renal cell carcinomas with antibodies to 2 splice variants of CD44, CD44v3 and CD44v6. RESULTS: Increased staining of renal clear cell carcinomas with Mab2137 was observed in high grade versus low grade tumors (45% vs. 0%, P = 0.013), whereas increased staining of clear cell carcinomas with Hermes-3 was noted in high stage versus low stage tumors (40% vs. 0%, P = 0.006). Few tumors stained with antibodies to CD44v3. Although increased expression of the splice variant CD44v6 was noted in papillary versus clear cell carcinomas, and increased staining of papillary carcinomas with Mab2137 and with antibodies to CD44v6 was noted for low stage versus high stage tumors, these differences did not achieve statistical significance. Clinical follow-up of at least 43 months was available for 26 patients. Six of these patients (five with clear cell carcinoma and one with papillary carcinoma) developed progressive or recurrent disease. The primary tumors from all 5 patients with progressive or recurrent clear cell carcinoma showed staining with Mab2137, whereas the primary tumors from only 2 of the 15 patients with at least 43 months follow-up and no evidence of progressive or recurrent clear cell carcinoma (13%) showed staining with Mab2137 (P = 0.001). Alternatively, 5 of 7 clear cell carcinomas (71%) that stained with Mab2137 were from patients who subsequently developed recurrence or progression, compared with 0 of 13 clear cell carcinomas that did not stain. Similar findings were not observed for papillary carcinomas, which appeared to be biologically distinct from clear cell carcinomas. CONCLUSIONS: CD44S staining with Mab2137 correlates with progression or recurrence of clear cell renal cell carcinoma. CD44S may, therefore, play a pathogenetic role in tumor progression.

Adult↗

PubMed2000

In vitro and ex vivo hydrolysis rates of ethacrynate esters and their relationship to intraocular pressure in the rabbit eye.

Esters of ethacrynic acid and partial structural analogs were synthesized and evaluated for topical antiglaucoma activity in rabbits. Maximum activity was shown by analogs 2 and 6 (34% and 30% reduction in intraocular pressure recovery rate, respectively). Among the esters, only the ethyl ester (2) was found to be active; the methyl and n-propyl esters (1 and 3) were inactive. Analogs 1-3 were subjected to an estimation of physicochemical properties and chemical stability. However, no correlation was found to exist between the biological activity/inactivity and the physicochemical properties of the analogs. The analogs were evaluated for ex vivo hydrolysis using rabbit aqueous humor (AH), corneal (C) homogenate and iris-ciliary body (ICB) homogenate. For all tissues, the rate of enzymatic hydrolysis increased significantly with an increasing ester chain length. The ICB-mediated hydrolysis was the fastest among the three tissues for all of the analogs. The relationship between the rate constants for the tissue-mediated hydrolyses were: analog 1, ICB>C>AH; analog 2, ICB>C=AH and analog 3, ICB>AH>C. Apparent Michaelis-Menten kinetic parameters were determined for the three analogs using corneal homogenate. Analog 2 showed the highest v0 for all substrate concentrations studied. The conventional Michaelis-Menten equation did not fit the data as well as a sigmoidal model. Both fits of the data showed the fastest enzyme-mediated hydrolysis for analog 2. The parameters of the sigmoidal fit of the data correlated with the activity/inactivity of the analogs. The data indicate that the major factors responsible for the observed activity/inactivity are the differences in the corneal enzymatic hydrolysis of the esters in conjunction with the rapid dynamics of ocular prodrug absorption.

Administration, Topical↗

PubMed1981

Bone mineral content of the radius: good correlations with physicochemical determinations in iliac crest trabecular bone of normal and osteoporotic subjects.

Specific gravity, porosity index (physical parameters), hydroxyproline, calcium, magnesium, and phosphorus (chemical parameters) were determined in iliac crest trabecular bone of normal and osteoporotic subjects. These physical and chemical parameters were compared to bone mineral contents (BMC) measurements by x-ray photodensitometry of the radius. BMC values correlated negatively with porosity index, specific gravity, and degree of mineralization of trabecular bone matrix, which all increase with osteoporosis. There was a negative correlation between calcium and magnesium contents per net bone volume. "Distal" scans of the radius reflected better the axial skeleton mass than "proximal" scans, and physicochemical data correlated better with bone mineral content values than with bone mineral mass (BMM) values.

Adult↗

PubMed2002

A comprehensive endocrine description of Kennedy's disease revealing androgen insensitivity linked to CAG repeat length.

Our study aims to provide a comprehensive view of the endocrine features in Kennedy's disease (KD). Twenty-two men with KD underwent detailed endocrine investigations. Clinical signs of partial androgen resistance were present in more than 80% of the patients, with gynecomastia being the most prominent. Gynecomastia was postpubertal but appeared before muscular weakness in most cases. Thirteen patients had alteration of testicular exocrine function. Hormonal profile of partial androgen resistance was present in 86% of the patients, with an elevated testosterone level in 68%. Androgen insensitivity seems to appear later in life in KD, similar to the development of neurological signs. Although we confirm the previously reported correlation between the CAG repeat length and the early onset of the neurological disease, we describe a significant correlation between repeat length and the age of onset of gynecomastia as well as biological indexes of androgen insensitivity. This is supported by numerous in vitro data correlating variations in the CAG tract with androgen receptor activity; the longer the CAG repeats, the weaker the receptor transactivation. Ours is the first study to show such a clear and prominent pattern of androgen insensitivity in KD. In clinical practice, KD patients are often misdiagnosed as having amyotrophic lateral sclerosis. Careful examination of the endocrine component could avoid such a deleterious misdiagnosis.

Adult↗

PubMed1976

Female responsiveness to erotic films and the "ideal" erotic film from a feminine perspective.

Subjects were 20 volunteers randomly selected from all female undergraduate students attending a local university, who were 21 years of age or older, and living off campus. The stimuli consisted of seven films, of approximately 5 minutes duration each, which depicted various types of human sexual behavior. Themes included "romantic" heterosexual behavior, primarily genital heterosexual behavior, a mild, and an explicit form of group-sex behavior, a mild and explicit form of heterosexual sadomasochistic behavior, and male homosexuality. Subjects rated the degree of sexual arousal experienced for each film on a 50-point Likert scale. The order of presentation of the films for each subject was randomized, and all subjects participated individually with only a female experimenter present. Following the rating period, subjects completed the Sex Knowledge and Attitude Test (9). Finally, a structured interview was conducted to probe specific likes and dislikes with respect to the content of the films viewed. Results indicated that rank order ratings of the films, from most to least sexually stimulating, was: heterosexual, romantic; group-sex mild (two males and one female); heterosexual-genital; group-sex explicit (three males and three females); sadomasochism (mild); sadomasochism-explicit (forcing and brutal); and male homosexuality. One conclusion that the data led to was that females preferred and were significantly more sexually stimulated by films in which a male related to a female (even if the male was treating the female cruelly) than they were by homosexual stimuli involving two males together. Correlational data between the rating responses and the Sex Knowledge and Attitude Test yielded much information including significant negative correlations between ratings of both group-sex films and rejection of sexual myths. Also, significant positive correlations were found between rated degree of sexual stimulation for the heterosexual and the group-sex films and the consideration of pre- and extramarital relations as acceptable or even desirable.

Abortion, Spontaneous↗

PubMed1997

Tissue and species distribution of mRNA for the IKr-like K+ channel, erg.

The human K+ channel gene, HERG, has been linked to the type 2 form of the autosomal dominant long-QT syndrome and has been suggested to encode the fast component of the delayed rectifier K+ current (IKr) found in heart. To date, the published electrophysiological and pharmacological data on the Xenopus-expressed HERG are very similar but are not identical to those of the endogenous IKr. In an effort to provide a different type of correlative data on the relationship between erg and IKr. cDNA fragments of erg homologues from guinea pig, rabbit, human, dog, and rat were cloned and used to test for the presence of erg mRNA in cardiac tissue. RNase protection assays reveal that erg message is found in the hearts of all five species and that it is expressed uniformly throughout the heart. The erg transcript is expressed at relatively high levels, being approximately 50% more abundant than the most prevalent Kv-class K+ channel transcript in canine ventricle (Kv4.3) erg transcripts were found to have a wide tissue distribution in rat and are abundant in the brain, retina, thymus, and adrenal gland and are also found in skeletal muscle, lung, and cornea. Since there were no published reports of an IKr-like current in the rat heart, electrophysiological studies were performed to test whether the significant level of erg message in rat heart was correlated with the presence of an IKr-like current in rat. In isolated rat ventricular myocytes, an E-4031-sensitive current was observed, which is consistent with the presence of IKr. These results strengthen the link between erg and the native IKr in heart and suggest that erg may play an important role in other noncardiac tissues.

Amino Acid Sequence↗

PubMed1993

An evaluation of sexual behaviour change using statistical and cognitive models. The AIDS Community Demonstration Projects.

We evaluate sexual behaviour change among homosexual men enrolled in the cohorts in four AIDS Community Demonstration Projects. Behaviour change is classified following the stages of behaviour change model and described using a Markov model. Predictors of behaviour change are identified and evaluated using logit models for correlated data. Sexual behaviour change within the cohort could be modelled as a first-order Markov process. In addition, predictors suggested by models of health behaviour were correlated with particular patterns of sexual behaviour change. Our evaluation revealed a variety of patterns of sexual behaviour change in the cohorts and suggests multi-faceted interventions for promotion of behaviour change.

Adult↗

PubMed2006

Prediction of breast tumor size by mammography and sonography--A breast screen experience.

Concise preoperative assessment of breast Tumor size is important when considering surgical approach and the staging of breast cancer. A retrospective study of 400 uni-focal, invasive ductal carcinomas compared the accuracy of sonographic and mammographic measuring modalities with histological size. Sub-groups for tumor size, type and grade, with other variables, were also considered in intra-modal correlations of lesion dimension. Mammography (R2=0.74), although slightly over estimating tumor size, appeared to be more useful than sonography (R2=0.60) following logistical analysis of the data. Correlational significance for both imaging modalities decreased for tumors larger than 20mm. Sonography under estimated lesions in over 50% of cases; the average underestimate being 9.9 mm, and ranging from 1mm to 30 mm. Consideration of both imaging measurements in cohort should improve the accuracy of radiological reporting of pre-surgical tumor size.

Adult↗

PubMed2005

Biosorption of nickel(II) ions onto Sargassum wightii: application of two-parameter and three-parameter isotherm models.

Biosorption of nickel(II) ions from aqueous solution onto Sargassum wightii has been studied and the equilibrium isotherms were determined. The experimental data obtained at different pH conditions (pH 3.0-4.5) have been analyzed using five two-parameter models (Langmuir, Freundlich, Temkin, Dubinin-Radushkevich and Flory-Huggins) and five three-parameter models (Redlich-Peterson, Sips, Khan, Radke-Prausnitz and Toth). In order to determine the best fit isotherm, three error analysis methods were used to evaluate the data: correlation coefficient, residual root mean square error and chi-square test. The error analysis demonstrated that the three-parameter models better described the nickel biosorption data compared to two-parameter models. In particular, Toth equation provided the best model for nickel biosorption data at all pH conditions examined.

Adsorption↗

PubMed2005

Porcine endogenous retroviruses PERV-A and PERV-B infect neither mouse cells in vitro nor SCID mice in vivo.

OBJECTIVE: Porcine endogenous retroviruses (PERVs) pose a risk for xenotransplantations using pig materials as they are present in the genome of all pigs and are able to infect human cells in vitro. Until recently, transmission of PERVs in vivo was only described in severe combined immunodeficient (SCID) and nude mice inoculated with PERV-producing cells. However, in this series of experiments microchimerism could not be excluded. To overcome this problem, the risk of PERV infection was addressed in a similar way but using cell-free inoculation of mouse cells in vitro and SCID mice in vivo. METHODS: Mouse cell lines and primary cells were incubated in vitro with PERV-A, with a recombinant PERV-A/C and with PERV-B. Provirus integration was assessed by PCR. Reverse transcriptase activity was measured in the cell supernatants. SCID mice were inoculated in vivo with cell-free virus at high titers. RESULTS: None of the mouse cell lines and primary cells could be infected by PERV and no provirus integration was observed in different organs of the inoculated SCID mice. CONCLUSION: The data indicate that PERV-A, PERV-A/C and PERV-B could not infect different mouse cells. These data correlate with the recent finding that mouse cells lack a functional receptor for PERV-A. Although the receptor for PERV-B is still unknown, these data suggest that previously reported PERV transmissions to SCID and nude mice in vivo might be due to microchimerism or pseudotyping with murine viruses and indicate that normal mice are an inappropriate model for the study of PERV infection and pathogenesis.

3T3 Cells↗

PubMed1984

Assay of metronidazole by HPLC compared with microbial method.

A high-performance liquid chromatography (HPLC) method for the assay of metronidazole and its 2-hydroxymethyl metabolite in sera was compared with a microbiological method, an agar well diffusion technique with Clostridium perfringens as indicator strain. The HPLC technique involves separation of metronidazole from its two active major metabolites (the 2-hydroxymethyl and the 1-carboxymethyl derivatives) on a mu-Bondapak C18 column and UV detection at 313 nm. The mobile phase was 35% acetonitrile in 0.02 M acetate buffer pH 4 with a low rate 2.0 ml/min. Tinidazole was used as an internal standard and metronidazole and its 2-hydroxymethyl metabolite quantitated by peak height ratios. The 1-carboxymethyl derivative was well separated from the other peaks. The HPLC procedure proved to be superior with respect to sensitivity (detection limits: 0-1 microgram/ml serum for both compounds), speed and precision. It discriminates between metronidazole and its two major active metabolites and quantitates the total amounts present. The microbial technique codetermines all antibacterial active compounds and monitors the free, not protein bound moieties. Published data on the activity of the 2-hydroxymethyl metabolite against Cl. perfringens relative to metronidazole and published results on the protein binding of metronidazole were used to correlate data from the two methods on individual serum samples collected during the early, intermediate and late periods after a single intravenous dose of metronidazole to volunteers.

Bacteriological Techniques↗

PubMed1998

Isozyme-selective metabolism of ethyl carbamate by cytochrome P450 (CYP2E1) and carboxylesterase (hydrolase A) enzymes in murine liver microsomes.

Cytochrome P450 and carboxylesterase enzymes have been implicated in the metabolism of the carcinogen ethyl carbamate (EC). In this study, we have used a murine liver microsomal system to investigate the relative contributions of P450 and carboxylesterase isozymes to hepatic metabolism of EC. N-Nitrosodimethylamine (NDMA) demethylation and p-nitrophenyl acetate (PNA) hydrolysis were used as catalytic markers of CYP2E1 and carboxylesterase enzymes, respectively. Incubation of liver microsomes with EC (1 mM) produced slight but significant decreases in NDMA demethylation and PNA hydrolysis activities. Incubation of microsomes with paraoxon (PAX), a general carboxylesterase inhibitor, or phenylmethylsulfonyl fluoride (PMSF), a specific inhibitor of hydrolase A, produced decreases of 85 and 45%, respectively, in carboxylesterase activities; neither of the inhibitors elicited alterations in levels of NDMA demethylation. Reaction of microsomes with either PAX or PMSF and then with EC exacerbated the reduction (285%) of NDMA demethylation, and this loss corresponded to decreases in immunodetectable CYP2E1 content. The reduction in PNA hydrolysis activity induced by PAX, PMSF, or EC correlated with decreased immunodetectable hydrolase A in liver microsomes; however, reaction with PAX and not PMSF or EC resulted in loss of immunoreactivity for hydrolase B. These data correlated with levels of covalent binding of [ethyl-14C]EC to liver microsomes, which were significantly elevated in incubations conducted with PAX or PMSF. Antibody inhibition of the CYP2E1 enzyme significantly reduced levels of binding to microsomal proteins, compared with control levels. These results are consistent with the premise that EC is metabolized by CYP2E1 and hydrolase A in liver microsomes of mice.

Animals↗

PubMed2006

Hypothalamic abnormalities in schizophrenia: sex effects and genetic vulnerability.

BACKGROUND: This is a unique hypothalamic magnetic resonance imaging (MRI) study in schizophrenia, an important region in the limbic system. We hypothesized abnormal volumetric increases, with greater severity in multiplex families (more than one ill member) compared with simplex families (one ill). We tested the hypothesis that normal hypothalamic sexual dimorphism is disrupted in schizophrenia. METHODS: Eighty-eight DSM-III-R schizophrenia cases (40 simplex and 48 multiplex), 43 first-degree nonpsychotic relatives, and 48 normal comparisons systematically were compared. A 1.5-Tesla General Electric scanner was used to acquire structural MRI scans, and contiguous 3.1-mm slices were used to segment anterior and posterior hypothalamus. General linear model for correlated data and generalized estimating equations were used to compare cases, relatives, and controls on right and left hypothalamus, controlled for age, sex, and total cerebral volume. Spearman's correlations of hypothalamic volumes with anxiety were calculated to begin to examine arousal correlates with structural abnormalities. RESULTS: Findings demonstrated significantly increased hypothalamic volume in cases and nonpsychotic relatives, particularly in regions of paraventricular and mammillary body nuclei, respectively. This increase was linear from simplex to multiplex cases, was positively correlated with anxiety, and had a greater propensity in women. CONCLUSIONS: Findings suggest important implications for understanding genetic vulnerability of schizophrenia and the high rate of endocrine abnormalities.

Adult↗

PubMed2006

Prediction of thermodynamic derivative properties of pure fluids through the Soft-SAFT equation of state.

We present in this work the application of the soft-SAFT equation of state (EoS) to the calculation of some main derivative properties, including heat capacities, reduced bulk modulus, Joule-Thomson coefficient, and speed of sound. Calculations have been performed analytically through the derivation of a primary thermodynamic potential function. The application to the n-alkanes, n-alkenes, and 1-alkanols families has been done in a semipredictive manner, with the molecular parameters of the equation obtained from previous fitting to vapor-liquid equilibrium data of the same compounds. The equation is able to capture the typical extrema isothermal derivative properties exhibit with respect to density, providing quantitative agreement with experimental (or correlation) data in some cases. Results in the vicinity of the critical point are improved by adding a crossover treatment to take into account the long-range fluctuations present in this region. By taking advantage of the molecular nature of the equation, we have been able to separate and quantify the different contributions (reference fluid, chain, and association) to the total derivative properties. The association plays a predominant role in energetic properties, such as the heat capacities, while there is a competition between association and chain length as the chain length of the compound increases for volumetric properties, such as the isothermal compressibility. These results act in favor of the molecular-based equations, like soft-SAFT, as predictive tools for several applications.

Journal Article↗

PubMed1985

Menaquinone composition of mycolic acid-containing actinomycetes and some sporoactinomycetes.

The menaquinones of 141 actinomycetes representing the genera Caseobacter, Mycobacterium, Nocardia, Rhodococcus and some related taxa lacking mycolic acids were examined by mass spectrometry. The mycolic acid-containing strains were assigned to four groups on the basis of the predominant isoprenologue detected: Rhodococcus coprophilus, R. equi, R. erythropolis, R. globerulus, R. rhodnii, R. rhodochrous and R. ruber contained dihydrogenated menaquinones with eight isoprene units; Nocardia asteroides, N. brasiliensis, N. carnea, N. otitidis-caviarum and N. transvalensis contained tetrahydrogenated menaquinones with eight isoprene units; Caseobacter polymorphus, R. bronchialis, R. rubropertinctus and R. terrae and representatives of twenty-one approved species of Mycobacterium contained dihydrogenated menaquinones with nine isoprene units; a single strain of 'Mycobacterium album', contained unsaturated menaquinones with nine isoprene units. Actinomycetes containing meso-diaminopimelic acid, arabinose and galactose in the wall peptidoglycan but lacking mycolic acids were recovered in two groups: tetrahydrogenated menaquinones with eight isoprene units were the main components from 'Nocardia' autotrophica and Pseudonocardia thermophila whereas Saccharopolyspora hirsuta and Pseudonocardia spp. contained tetrahydrogenated menaquinones with nine isoprene units. Promicromonospora citrea and 'skin coryneforms' with LL-diaminopimelic acid and glycine in the wall peptidoglycan also contained tetrahydrogenated menaquinones with nine isoprene units as the major isoprenologue. In contrast, representatives of the genera Kitasatoa, Microellobosporia, Streptomyces and Streptoverticillium were characterized by the presence of complex mixtures of tetra-, hexa- and octa-hydrogenated menaquinones with nine isoprene units. The menaquinone data correlate well with other developments in actinomycete systematics and confirm earlier suggestions that menaquinone analyses are of value in both the classification and identification of actinomycetes. Indeed, the data suggest that minimal descriptions of wall chemotype IV taxa should ideally include information on menaquinone composition.

Actinomycetales↗

PubMed2005

Remote sensing of sediment density and velocity gradients in the transition layer.

The geoacoustic properties of marine sediments, e.g., bulk density and compressional velocity, commonly exhibit large variations in depth near the water-sediment interface. This layer, termed the transition layer, is typically of 0(10(-1)-10(0)) m in thickness. Depth variations within the transition layer may have important implications for understanding and modeling acoustic interaction with the seabed, including propagation and reverberation. In addition, the variations may contain significant clues about the underlying depositional or erosional processes. Characteristics of the transition layer can be measured directly (e.g., coring) or remotely. Remote measurements have the advantage of sampling without disturbing the sediment properties; they also have the potential to be orders of magnitude faster and less expensive than direct methods. It is shown that broadband seabed reflection data can be exploited to remotely obtain the depth dependent density and velocity profiles in the transition layer to high accuracy. A Bayesian inversion approach, which accounts for correlated data errors, provides estimates and uncertainties for the geoacoustic properties. These properties agree with direct (i.e., core) measurements within the uncertainty estimates.

Journal Article↗

PubMed1989

Application of an erythrocyte aluminum assay in the diagnosis of aluminum-associated microcytic anemia in patients undergoing dialysis and response to deferoxamine therapy.

A method for measuring erythrocyte aluminum content was developed. Erythrocyte aluminum levels correlated with plasma aluminum concentrations in normal controls and in patients undergoing dialysis (r = 0.90, p less than 0.001). In vitro studies showed that erythrocyte aluminum concentrations were not altered by contamination of blood samples, which is a common problem with plasma determinations. The need for anticoagulation and rapid processing were disadvantages of this assay. In the dialysis population studied, the correlative data between mean cell volume and both plasma and erythrocyte aluminum levels (r = -0.50, p less than 0.001; and r = -0.69, p less than 0.001) and lack of correlation with serum ferritin suggested that aluminum overload and not iron deficiency was the cause of microcytic anemia. Patients undergoing continuous ambulatory peritoneal dialysis had lower plasma and erythrocyte aluminum levels and absence of microcytic anemia compared with patients undergoing hemodialysis. Therapy with deferoxamine in 13 patients with aluminum-related microcytic anemia resulted in a decrease in erythrocyte and plasma aluminum content in all patients (265.5 +/- 69.2 micrograms/L to 22.6 +/- 9.7 micrograms/L and 196 +/- 30 micrograms/L to 129 +/- 13.8 micrograms/L). The relatively smaller decrease in plasma aluminum levels suggested mobilization of aluminum from tissues other than erythrocytes. Aluminum chelation most probably occurred from premature erythrocytes, because in vitro studies showed that deferoxamine was unable to chelate aluminum from mature erythrocytes. Hemoglobin level, hematocrit measurement, and mean cell volume showed significant improvement (p less than 0.001). Ten patients showed normalized mean cell volume after 6.2 +/- 2 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

PubMed2005

Correlation function bootstrapping in quantum chaotic systems.

We discuss a general and efficient approach for "bootstrapping" short-time correlation data in chaotic or complex quantum systems to obtain information about long-time dynamics and stationary properties, such as the local density of states. When the short-time data are sufficient to identify an individual quantum system, we obtain a systematic approximation for the spectrum and wave functions. Otherwise, we obtain statistical properties, including wave function intensity distributions, for an ensemble of all quantum systems sharing the given short-time correlations. The results are valid for open or closed systems, and are stable under perturbation of the short-time input data. Numerical examples include quantum maps and two-dimensional anharmonic oscillators.

Journal Article↗