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Biomedical subjects

Ying Zhang

Publications and source records attributed to Ying Zhang.

At least 271 records · Page 15Linked to original sources

Tempol reduces reperfusion-induced arrhythmias in anaesthetized rats.

The generation of reactive oxygen species (ROS) contributes to reperfusion-induced arrhythmias. In the present study, the antiarrhythmic effects of tempol and tiron, two membrane-permeable radical scavengers, on reperfusion-induced arrhythmias in rats in vivo were investigated. The anaesthetized rats were subjected to 5 min of left descending coronary artery (LAD) occlusion followed by 30 min of reperfusion. All rats pretreated with saline developed ventricular tachycardia (VT) and ventricular fibrillation (VF) at the onset of reperfusion, and most of the rats died from irreversible VF at the end of reperfusion. However, pretreatment with tempol (30 or 100 mg kg(-1)) 5 min before reperfusion reduced mortality, arrhythmia score and the incidence and duration of VT and VF. In the rats pretreated with high dose of tempol (100 mg kg(-1)), no VF happened and all rats were alive at the end of the experiment. The arrhythmia score was also significantly decreased compared with that of rats pretreated with saline (0.80 +/- 0.4 versus 5.6 +/- 0.4, P < 0.01). Tiron also provided nearly complete protection against reperfusion-induced arrhythmias when given 2 min before reperfusion. On the other hand, intravenous administration of tempol induced decreases in mean arterial pressure (MAP), heart rate (HR) and pressure rate index (PRI), a relative indicator of myocardial oxygen consumption. In order to determine whether the antiarrhythmic effects of tempol were secondary to the reduction of myocardial oxygen consumption, continuous electrical stimulation of the aortic depressor nerve (3 V, 10 ms and 10 Hz) was carried out in a group of rats to induce decreases in MAP, HR and PRI similar to those in the high dose of Tempol group. However, these rats did not show significant changes in the severity of reperfusion-induced arrhythmias. We conclude that both tempol and tiron significantly reduce reperfusion-induced arrhythmias in rats, and this protective action is independent of hemodynamic effects.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

Monitoring of trifluoroacetic acid concentration in environmental waters in China.

It is critically important and extremely meaningful to determine the concentration of TFA in the environmental water in China. This will create background reference for the effects of analyzing the extensive employment of the substitutes to CFCs in China. In this paper a set of analytical methods was described for use in monitoring of trifluoroacetic acid (TFA) concentration of environmental waters including collecting, pre-treatment measures, preserving, concentrating and derivatization of samples from different kinds of environmental waters. The GC with electrical capture detector (ECD) and headspace auto sampler were used in the analysis. The lowest detection limit of the instrument is 0.0004 ng methyl trifluoroacetic acid (MTFA), and the lowest detected concentration with the method is 3.0 ng/ml TFA. TFA collected in various environmental water samples (including rainfall, inland surface water, ground water, and waste water) from nine provinces and autonomous regions in China have been determined by applying the analytical methods created and defined in this work. The results indicate that the concentrations of TFA in nine rainfalls and three snowfalls through the period from 2000 to 2001 ranged from 25 to 220 ng/l, the TFA concentration in the inland surface water samples ranged from 4.7 to 221 ng/l, the concentration of TFA in groundwater samples collected in Beijing was 10 ng/l, and the TFA concentration in coastal water samples ranged from 4.2 to 190.1 ng/l.

China↗

Regional heterogeneity for the intracranial self-administration of ethanol and acetaldehyde within the ventral tegmental area of alcohol-preferring (P) rats: involvement of dopamine and serotonin.

The meso-limbic dopamine (DA) system has an important role in regulating alcohol drinking. Previous findings from our laboratory indicated that Wistar rats self-administered ethanol (EtOH) directly into the posterior, but not anterior, ventral tegmental area (VTA), and that coadministration of a DA D(2,3) receptor agonist or a serotonin-3 (5-HT3) receptor antagonist blocked EtOH self-administration. In addition, we reported that alcohol-preferring (P) rats self-administered acetaldehyde (ACD), the first metabolite of EtOH, into the posterior VTA. The objectives of this study were to compare the reinforcing effects of EtOH and ACD within the VTA of P rats to examine the possibility that the reinforcing effects of EtOH within the VTA may be mediated by its conversion to ACD. Adult female P rats were stereotaxically implanted with guide cannulae aimed at either the posterior or anterior VTA. At 1 week after surgery, rats were placed in standard two-lever (active and inactive) experimental chambers for a total of seven to eight sessions. The 4-h sessions were conducted every other day. The results indicated that (a) 75-300 mg% (17-66 mM) EtOH and 6-90 microM ACD were self-administered into the posterior, but not anterior, VTA; (b) the self-administration of 150 mg% EtOH was not altered by coinfusion of a catalase inhibitor; (c) coadministration of the D(2/3) agonist quinpirole (100 microM) blocked the self-infusions of 150 mg% EtOH and 23 microM ACD into the posterior VTA; and (d) coadministration of 200 microM ICS205,930 (5-HT3 receptor antagonist) prevented the self-infusion of 150 mg% EtOH, whereas concentrations of ICS 205,930 up to 400 microM had no effect on the self-infusion of 23 microM ACD into the posterior VTA. Overall, the results of this study indicate that EtOH and ACD can independently produce reinforcing effects within the posterior VTA, and that activation of DA neurons mediates these effects. Furthermore, activation of 5-HT3 receptors within the posterior VTA is involved in the self-infusion of EtOH, but not ACD.

Acetaldehyde↗

Molecular character of the recombinant antitumor lectin from the edible mushroom Agrocybe aegerita.

The lectin from Agrocybe aegerita (AAL) has been found to possess potent tumor-suppressing function and tumor cell apoptosis-inducing activity. In this paper, we report the full sequence, the active expression of the gene encoding AAL at a high level and bioassay of the binding property with lactose, apoptosis-inducing activity and DNase activity of recombinant AAL (rAAL). The results reveal that AAL is a member of the galectin family and the dimeric form is the active unit for the functional performance. The rAAL showed comparable tumor cell apoptosis-inducing activity with the wild AAL but no DNase activity at all. The molecular characters revealed by this study are significant for the in-depth investigation of the functional mechanism of this interesting protein.

Agaricales↗

Microarray-based pncA genotyping of pyrazinamide-resistant strains of Mycobacterium tuberculosis.

Drug-resistant Mycobacterium tuberculosis poses a significant threat to the treatment of tuberculosis (TB). The current susceptibility testing for the first-line TB drug pyrazinamide (PZA) is not only time-consuming but also difficult, due to the requirement for acid pH for drug activity. Predominantly, resistance to PZA in M. tuberculosis is caused by mutations in the pncA gene, and the detection of pncA mutations can be an indicator of PZA resistance. In this study, the use of a previously developed microarray method for the rapid detection of PZA-resistant M. tuberculosis based on identifying mutations in the pncA gene was evaluated. Microarray analysis was performed in a blind manner on 33 clinical isolates of M. tuberculosis for which the sequence of the pncA gene had not previously been determined. The results showed that all mutations in PZA-resistant strains identified by DNA sequencing could be unambiguously detected by the microarray method. It is concluded that the microarray method is a valuable tool for the rapid screening and genetic identification of potential PZA-resistant M. tuberculosis strains.

Amidohydrolases↗

Stochastic dietary restriction using a Markov-chain feeding protocol elicits complex, life history response in medflies.

Lifespan in individually housed medflies (virgins of both sexes) and daily reproduction for females were studied following one of 12 dietary restriction (DR) treatments in which the availability of high-quality food (yeast-sugar mixture) for each fly was based on a Markov chain feeding scheme--a stochastic dietary regime which specifies that the future dietary state depends only on the present dietary state and not on the path by which the present state was achieved. The stochastic treatments consisted of a combination of one of four values of a 'discovery' parameter and one of three values of a 'persistence' parameter. The results supported the hypotheses that: (i) longevity is extended in most medfly cohorts subject to stochastic DR; and (ii) longevity is more affected by the patch discovery than the patch persistence parameter. One of the main conclusions of the study is that, in combination with the results of earlier dietary restriction studies on the medfly, the results reinforce the concept that the details of the dietary restriction protocols have a profound impact on the sign and magnitude of the longevity extension relative to ad libitum cohorts and that a deeper understanding of the effect of food restriction on longevity is not possible without an understanding of its effect on reproduction.

Age Factors↗

Characteristics of Chinese patients with Wegener's granulomatosis with anti-myeloperoxidase autoantibodies.

BACKGROUND: Cytoplasmic antineutrophil cytoplasmic autoantibodies (cANCA)/proteinase-3(PR3)-ANCA was considered the serologic diagnostic marker for Wegener's granulomatosis (WG). However, Chinese patients with MPO-ANCA positive WG were frequently diagnosed. We now analyze the characteristics of patients with MPO-ANCA positive WG and investigate the difference between patients with MPO-ANCA and PR3-ANCA. METHODS: Patients with WG were selected according to both Chapel Hill Consensus Conference definition and American College of Rheumatology (ACR) classification criteria in 500 Chinese patients with ANCA-associated systemic vasculitides. The clinical manifestions were compared between patients with MPO-ANCA and with PR3-ANCA. RESULTS: Eight-nine patients fulfilled the diagnostic criteria of WG: 54/89(60.7%) were MPO-ANCA positive, 34/89(38.2%) were PR3-ANCA positive. Patients with MPO-ANCA were predominantly female compared with patients with PR3-ANCA. Patients with MPO-ANCA also had multisystem involvement. However, the prevalences of arthagia, skin rash, ophthalmic and ear involvement were significantly lower in patients with MPO-ANCA than those in patients with PR3-ANCA (46.3% vs. 70.6%, P < 0.05; 20.4% vs. 44.1%, P < 0.05; 27.8% vs. 58.8%, P < 0.01; 40.7% vs. 67.6%, P < 0.05, respectively). The prevalence of elevated initial serum creatinine was significantly higher in patients with MPO-ANCA than that in patients with PR3-ANCA (81.5% vs. 61.8%, chi(2) = 4.20, P < 0.05). CONCLUSION: Patients with MPO-ANCA positive WG were not rare in Chinese.

Adolescent↗

Nursing home practitioner survey of diagnostic criteria for urinary tract infections.

OBJECTIVES: To identify clinical and laboratory criteria used by nursing home practitioners for diagnosis and treatment of urinary tract infections (UTIs) in nursing home residents. To determine practitioner knowledge of the most commonly used consensus criteria (i.e., McGeer criteria) for UTIs. DESIGN: Self-administered survey. SETTING: Three New Haven-area nursing homes. PARTICIPANTS: Physicians (n=25), physician assistants (PAs, n=3), directors/assistant directors of nursing (n=8), charge nurses (n=37), and infection control practitioners (n=3). MEASUREMENTS: Open- and closed-ended questions. RESULTS: Nineteen physicians, three PAs, and 41 nurses completed 63 of 76 (83%) surveys. The five most commonly reported triggers for suspecting UTI in noncatheterized residents were change in mental status (57/63, 90%), fever (48/63, 76%), change in voiding pattern (44/63, 70%), dysuria (41/63, 65%), and change in character of urine (37/63, 59%). Asked to identify their first diagnostic step in the evaluation of UTIs, 48% (30/63) said urinary dipstick analysis, and 40% (25/63) said urinalysis and urine culture. Fourteen of 22 (64%) physicians and PAs versus 40 of 40 (100%) nurses were aware of the McGeer criteria for noncatheterized patients (P<.001); 12 of 22 (55%) physicians and PAs versus 38 of 39 (97%) nurses used them in clinical practice (P<.001). CONCLUSION: Although surveillance and treatment consensus criteria have been developed, there are no universally accepted diagnostic criteria. This survey demonstrated a distinction between surveillance criteria and criteria practitioners used in clinical practice. Prospective data are needed to develop evidence-based clinical and laboratory criteria of UTIs in nursing home residents that can be used to identify prospectively tested treatment and prevention strategies.

Aged↗

A chart-based method for identification of delirium: validation compared with interviewer ratings using the confusion assessment method.

OBJECTIVES: To validate a chart-based method for identification of delirium and compare it with direct interviewer assessment using the Confusion Assessment Method (CAM). DESIGN: Prospective validation study. SETTING: Teaching hospital. PARTICIPANTS: Nine hundred nineteen older hospitalized patients. MEASUREMENTS: A chart-based instrument for identification of delirium was created and compared with the reference standard interviewer ratings, which used direct cognitive assessment to complete the CAM for delirium. Trained nurse chart abstractors were blinded to all interview data, including cognitive and CAM ratings. Factors influencing the correct identification of delirium in the chart were examined. RESULTS: Delirium was present in 115 (12.5%) patients according to the CAM. Sensitivity of the chart-based instrument was 74%, specificity was 83%, and likelihood ratio for a positive result was 4.4. Overall agreement between chart and interviewer ratings was 82%, kappa=0.41. By contrast, using International Classification of Diseases, Ninth Revision, Clinical Modification, administrative codes, the sensitivity for delirium was 3%, and specificity was 99%. Independent factors associated with incorrect chart identification of delirium were dementia, severe illness, and high baseline delirium risk. With all three factors present, the chart instrument was three times more likely to identify patients incorrectly than with none of the factors present. CONCLUSION: A chart-based instrument for delirium, which should be useful for patient safety and quality-improvement programs in older persons, was validated. Because of potential misclassification, the chart-based instrument is not recommended for individual patient care or diagnostic purposes.

Aged↗

Consequences of preventing delirium in hospitalized older adults on nursing home costs.

OBJECTIVES: To determine whether costs of long-term nursing home (NH) care for patients who received a multicomponent targeted intervention (MTI) to prevent delirium while hospitalized were less than for those who did not receive the intervention. DESIGN: Longitudinal follow-up from a randomized trial. SETTING: Posthospital discharge settings: community-based care and NHs. PARTICIPANTS: Eight hundred one hospitalized patients aged 70 and older. MEASUREMENTS: Patients were followed for 1 year after discharge, and measures of NH service use and costs were constructed. Total long-term NH costs were estimated using a two-part regression model and compared across intervention and control groups. RESULTS: Of the 400 patients in the intervention group and 401 patients in the matched control group, 153 (38%) and 148 (37%), respectively, were admitted to a NH during the year, and 54 (13%) and 51 (13%), respectively, were long-term NH patients. The MTI had no effect on the likelihood of receiving long-term NH care, but of patients receiving long-term NH care, those in the MTI group had significantly lower total costs, shorter length of stay and lower cost per survival day. Adjusted total costs were $50,881 per long-term NH patient in the MTI group and $60,327 in the control group, a savings of 15.7% (P=.01). CONCLUSION: Active methods to prevent delirium are associated with a 15.7% decrease in long-term NH costs. Shorter length of stay of patients receiving long-term NH services was the primary source of these savings.

Activities of Daily Living↗

Time-varying functional regression for predicting remaining lifetime distributions from longitudinal trajectories.

A recurring objective in longitudinal studies on aging and longevity has been the investigation of the relationship between age-at-death and current values of a longitudinal covariate trajectory that quantifies reproductive or other behavioral activity. We propose a novel technique for predicting age-at-death distributions for situations where an entire covariate history is included in the predictor. The predictor trajectories up to current time are represented by time-varying functional principal component scores, which are continuously updated as time progresses and are considered to be time-varying predictor variables that are entered into a class of time-varying functional regression models that we propose. We demonstrate for biodemographic data how these methods can be applied to obtain predictions for age-at-death and estimates of remaining lifetime distributions, including estimates of quantiles and of prediction intervals for remaining lifetime. Estimates and predictions are obtained for individual subjects, based on their observed behavioral trajectories, and include a dimension-reduction step that is implemented by projecting on a single index. The proposed techniques are illustrated with data on longitudinal daily egg-laying for female medflies, predicting remaining lifetime and age-at-death distributions from individual event histories observed up to current time.

Animals↗

Evaluation of recombinant lipidated P2086 protein as a vaccine candidate for group B Neisseria meningitidis in a murine nasal challenge model.

Neisseria meningitidis is a major causative agent of bacterial meningitis in human beings, especially among young children (</=2 years of age). Prevention of group B meningococcal disease represents a particularly difficult challenge in vaccine development, due to the inadequate immune response elicited against type B capsular polysaccharide. We have established an adult mouse intranasal challenge model for group B N. meningitidis to evaluate potential vaccine candidates through active immunization. Swiss Webster mice were inoculated intranasally with meningococci, and bacteria were recovered from the noses for at least 3 days postchallenge. Iron dextran was required in the bacterial inoculum to ensure sufficient meningococcal recovery from nasal tissue postchallenge. This model has been utilized to evaluate the potential of a recombinant lipidated group B meningococcal outer membrane protein P2086 (rLP2086) as a vaccine candidate. In this study, mice were immunized subcutaneously with purified rLP2086 formulated with or without an attenuated cholera toxin as an adjuvant. The mice were then challenged intranasally with N. meningitidis strain H355 or M982, and the colonization of nasal tissue was determined by quantitative culture 24 h postchallenge. We demonstrated that immunization with rLP2086 significantly reduced nasal colonization of mice challenged with the two different strains of group B N. meningitidis. Mice immunized with rLP2086 produced a strong systemic immunoglobulin G response, and the serum antibodies were cross-reactive with heterologous strains of group B N. meningitidis. The antibodies have functional activity against heterologous N. meningitidis strain, as demonstrated via bactericidal and infant rat protection assays. These results suggest that rLP2086 is a potential vaccine candidate for group B N. meningitidis.

Adoptive Transfer↗

PppA, a surface-exposed protein of Streptococcus pneumoniae, elicits cross-reactive antibodies that reduce colonization in a murine intranasal immunization and challenge model.

The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine. However, serotypes not covered by the present conjugate vaccine may still cause pneumococcal disease. To address these serotypes, and the remaining otitis media due to Streptococcus pneumoniae, efforts have been devoted to identifying protective protein antigens. Immunity to conserved surface proteins important for adhesion, nutrient acquisition, or other functions could result in a reduction of colonization and a lower disease potential. We have been searching for conserved surface-exposed proteins from S. pneumoniae that may be involved in pathogenesis to test as vaccine candidates. Here, an approximately 20-kDa protein that has significant homology to a nonheme iron-containing ferritin protein from Listeria innocua and other bactoferritins was identified as pneumococcal protective protein A (PppA). We expressed and purified recombinant PppA (rPppA) and evaluated its potential as a vaccine candidate. The antibodies elicited by purified rPppA were cross-reactive with PppA from multiple strains of S. pneumoniae and were directed against surface-exposed epitopes. Intranasal immunization of BALB/c mice with PppA protein and either a synthetic monophosphoryl lipid A analog, RC529AF, or a cholera toxin mutant, CT-E29H, used as an adjuvant reduced nasopharyngeal colonization in mice following intranasal challenge with a heterologous pneumococcal strain. PppA-specific systemic and local immunoglobulin G (IgG) and IgA antibody responses were induced. The antisera reacted with whole cells of a heterologous S. pneumoniae type 3 strain. These observations indicate that PppA may be a promising candidate for inclusion in a vaccine against pneumococcal otitis media.

Administration, Intranasal↗

Coordinated changes in DNA methylation and histone modifications regulate silencing/derepression of luteinizing hormone receptor gene transcription.

We have previously demonstrated that transcription of the luteinizing hormone receptor (LHR) gene is subject to repression by histone deacetylation at its promoter region, where a histone deacetylase (HDAC)/mSin3A complex is anchored at a proximal Sp1 site. The present studies have shown that epigenetic silencing and activation of the LHR gene is achieved through coordinated regulation at both the histone and DNA levels. The HDAC inhibitor trichostatin A (TSA) evoked robust but significantly lower activation of the LHR gene in JAR than in MCF-7 cells. This effect was localized to the 176-bp promoter region, which is highly methylated in JAR and lightly methylated in MCF-7 cells. Consequently, TSA and the DNA demethylating reagent 5-azacytidine (5-AzaC) caused marked synergistic activation of the LHR gene in JAR but not in MCF-7 cells. Multiple site-specific lysine acetylation of H3/H4 is associated with such LHR gene activation. Methylation or acetylation of H3 at K9 is present at the silenced and derepressed LHR promoter, respectively. While DNA methylation levels did not affect the histone code of the LHR gene promoter, demethylation of the promoter CpG sites was necessary for maximal stimulation of this gene. Mechanistically, the combined actions of TSA and 5-AzaC, but not either 5-AzaC or TSA alone, resulted in complete demethylation of the LHR gene promoter in JAR cells. Release of the repressive HDAC/mSin3A complex from the LHR gene promoter in both cell types required both TSA-induced changes of histone modifications and, concurrently, a demethylated promoter. Also, Dnmt1 was largely dissociated from the LHR gene promoter in the presence of TSA or TSA plus 5-AzaC, and binding of MBD2 in JAR cells was diminished upon conversion of the promoter to a demethylated state. Such changes induced a more permissive chromatin where recruitment of polymerase II and TFIIB to the promoter was significantly increased. The activated state of the LHR gene induced by TSA and 5-AzaC in JAR and MCF-7 cells was observed basally in LHR-expressing PLC cells, in which the promoter is unmethylated and associated with hyperacetylated histones. Consequently, PLC cells are unresponsive to drug treatment. These findings have elucidated a regulatory mechanism whereby concurrent dissociation of repressors and association of activators and basal transcriptional components, resulting from coordinated histone hyperacetylation and DNA demethylation, lead to derepression of the LHR gene expression.

Acetylation↗

The magic bullets and tuberculosis drug targets.

Modern chemotherapy has played a major role in our control of tuberculosis. Yet tuberculosis still remains a leading infectious disease worldwide, largely owing to persistence of tubercle bacillus and inadequacy of the current chemotherapy. The increasing emergence of drug-resistant tuberculosis along with the HIV pandemic threatens disease control and highlights both the need to understand how our current drugs work and the need to develop new and more effective drugs. This review provides a brief historical account of tuberculosis drugs, examines the problem of current chemotherapy, discusses the targets of current tuberculosis drugs, focuses on some promising new drug candidates, and proposes a range of novel drug targets for intervention. Finally, this review addresses the problem of conventional drug screens based on inhibition of replicating bacilli and the challenge to develop drugs that target nonreplicating persistent bacilli. A new generation of drugs that target persistent bacilli is needed for more effective treatment of tuberculosis.

Animals↗

Vasodilatation produced by orientin and its mechanism study.

In this paper we investigated the vascular activity and possible mechanism of Orientin, from bamboo leaves (Phyllostachys nigra), in isolated thoracic aortic rings from New Zealand rabbit. Among the four compounds, studied, only Orientin relaxed phenylephrine-induced contractions with an IC50 value of 2.28 microM in the endothelium intact and with an IC50 value around 7.27 microM in the endothelium removed aortic rings. The vasorelaxant effect of Orientin on endothelium-intact thoracic aortic rings was attenuated by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester, but not by indomethacin (a cyclooxygenase inhibitor), tetraethylammonium chloride (K+ channels inhibitor) or propranolol (beta-receptor inhibitor). Furthermore, Orientin inhibited norepinephrine (NE), CaCl2 and KCl-induced vasoconstriction concentration dependently in a non-competitive manner, and also reduced both the initial fast release and the sustained phases of phenylephrine-induced contractions. Orientin can stimulate NO production from endothelial cells. Orientin also increased cyclic guanosine 3,5-cyclic monophosphate (cGMP) levels without changes in adenosine-3',5'-cyclic phosphoric acid (cAMP) in rabbit aorta. The results showed that Orientin relaxed thoracic aortic rings by the nitric oxide-cGMP pathway, and in the vascular smooth muscle inhibited the contraction induced by the activation of receptor-operating and voltage-dependent Ca2+ channels. Cyclooxygenase pathway, potassium channels, beta-receptors and cAMP pathway, on the other hand, had no apparent roles. The inhibition of both intracellular Ca2+ release and extracellular Ca2+ influx may be one of the main vasorelaxant mechanisms of Orientin.

Animals↗

Adaptive autofocusing: a closed-loop perspective.

We present an adaptive autofocusing scheme. In this scheme, the focus measure is updated with focus tuning. To achieve this, we construct the focus measure by using image moments and develop an adaptive focus-tuning strategy to estimate the measure in closed loop. It is shown that the adaptive updating of the focus measure enables us to overcome the dependence of autofocusing on the image contents. Such an adaptive closed-loop focusing operation also effectively suppresses both the effect of the noise in optical imaging and the effect of time delay due to image processing time. Therefore a high accuracy of autofocusing is guaranteed. The effectiveness of the proposed scheme is demonstrated by simulations and experiments.

Algorithms↗