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Biomedical subjects

A Basu

Publications and source records attributed to A Basu.

At least 55 records · Page 3Linked to original sources

Weak and strong dynamic scaling in a one-dimensional driven coupled-field model: effects of kinematic waves.

We study the coupled dynamics of the displacement fields in a one-dimensional coupled-field model for drifting crystals, first proposed by Lahiri and Ramaswamy [Phys. Rev. Lett. 79, 1150 (1997)]. We present some exact results for the steady state and the current in the lattice version of the model for a special subspace in the parameter space, within the region where the model displays kinematic waves. We use these results to construct the effective continuum equations corresponding to the lattice model. These equations decouple at the linear level in terms of the eigenmodes. We examine the long-time, large-distance properties of the correlation functions of the eigenmodes by using symmetry arguments, Monte Carlo simulations, and self-consistent mode-coupling methods. For most parameter values, the scaling exponents of the Kardar-Parisi-Zhang equation are obtained. However, for certain symmetry-determined values of the coupling constants the two eigenmodes, although nonlinearly coupled, are characterized by two distinct dynamic exponents. We discuss the possible application of the dynamic renormalization group in this context.

Journal Article↗

Differential sensitivity of breast cancer cells to tumor necrosis factor-alpha: involvement of protein kinase C.

We have compared several breast cancer cell lines that differ in their responsiveness to TNF to determine the involvement of PKC isozymes in regulating sensitivity of breast cancer cells to TNF. While MCF-7 and BT-20 cells were responsive to TNF without any metabolic inhibitors, CAMA-1 and SKBR-3 cells responded to TNF in the presence of cycloheximide; MDA-MB-231 and Hs578t cells were resistant to TNF even in the presence of cycloheximide. Bisindolylmaleimide (BIM), an inhibitor of PKC, either alone (MCF-7 and BT-20) or in combination with cycloheximide enhanced sensitivity of these cells to TNF. The PKC isozyme profile of MCF-7 cells was similar to BT-20 cells and that of CAMA-1 cells was similar to SKBR-3 cells. MCF-7, BT-20 and MDA-MB-231 cells that were most responsive to BIM-mediated sensitization to TNF contained relatively high level of PKC epsilon and proteolytic cleavage of PKC epsilon correlated with TNF-induced cell death. BIM did not inhibit NF-kappa B activation by TNF but caused activation of caspases and enhanced cleavage of PKC delta and -epsilon. These results suggest that proteolytic cleavage of PKC epsilon may be associated with PKC inhibitor mediated sensitization of breast cancer cells to TNF.

Antimetabolites↗

Type I diabetes mellitus does not alter initial splanchnic glucose extraction or hepatic UDP-glucose flux during enteral glucose administration.

AIMS/HYPOTHESIS: Our aim was to determine whether an alteration in splanchnic glucose metabolism could contribute to postprandial hyperglycaemia in people with Type I (insulin-dependent) diabetes mellitus. METHODS: Splanchnic glucose extraction, hepatic glycogen synthesis and endogenous glucose production were compared in 8 Type I diabetic patients and in 11 control subjects. Endogenous hormone secretion was inhibited with somatostatin while insulin (approximately 550 pmol/l) and glucagon (approximately 130 ng/l) concentrations were matched with exogenous hormone infusions. Glucose containing [3-3H] glucose was infused into the duodenum at a rate of 20 micromol.kg(-1).min(-1). Plasma glucose concentrations were maintained at about 8.5 mmol/l in both groups by means of a separate variable intravenous glucose infusion. RESULTS: Initial splanchnic glucose uptake, calculated by subtracting the systemic rate of appearance of [3-3H] glucose from the rate of infusion of [3-3H] glucose into the duodenum, did not differ in the diabetic and non-diabetic patients (4.1 +/- 0.8 vs 3.0 +/- 1.0 micromol/kg/min). In addition, hepatic glycogen synthesis, measured using the acetaminophen glucuronide method did not differ (10.7 +/- 2.4 vs 10.1 +/- 2.7 micromol.kg(-1).min(-1)). On the other hand, suppression of endogenous glucose production, measured by an intravenous infusion of [6,6-2H2] glucose, was greater (p < 0.05) in the diabetic than in the non-diabetic subjects (1.7 +/- 1.6 vs 5.8 +/- 1.9 micromol.kg(-1).min(-1)). CONCLUSION/INTERPRETATION: When glucose, insulin and glucagon concentrations are matched in individuals with relatively good chronic glycaemic control, Type I diabetes does not alter initial splanchnic glucose uptake of enterally delivered glucose or hepatic glycogen synthesis. Alterations in splanchnic glucose metabolism are not likely to contribute to postprandial hyperglycaemia in people with well controlled Type I diabetes.

Blood Glucose↗

Genomic structures and population histories of linguistically distinct tribal groups of India.

There are various conflicting hypotheses regarding the origins of the tribal groups of India, who belong to three major language groups--Austro-Asiatic, Dravidian and Tibeto-Burman. To test some of the major hypotheses we designed a genetic study in which we sampled tribal populations belonging to all the three language groups. We used a set of autosomal DNA markers, mtDNA restriction-site polymorphisms (RSPs) and mtDNA hypervariable segment-1 (HVS-1) sequence polymorphisms in this study. Using the unlinked autosomal markers we found that there is a fair correspondence between linguistic and genomic affinities among the Indian tribal groups. We reconstructed mtDNA RSP haplotypes and found that there is extensive haplotype sharing among all tribal populations. However, there is very little sharing of mtDNA HVS-1 sequences across populations, and none across language groups. Haplogroup M is ubiquitous, and the subcluster U2i of haplogroup U occurs in a high frequency. Our analyses of haplogroup and HVS-1 sequence data provides evidence in support of the hypothesis that the Austro-Asiatic speakers are the most ancient inhabitants of India. Our data also support the earlier finding that some of the western Eurasian haplogroups found in India may have been present in India prior to the entry of Aryan speakers. However, we do not find compelling evidence to support the theory that haplogroup M was brought into India on an "out of Africa" wave of migration through a southern exit route from Ethiopia. On the contrary, our data raise the possibility that this haplogroup arose in India and was later carried to East Africa from India.

DNA, Mitochondrial↗

Genetic toxicology of a paradoxical human carcinogen, arsenic: a review.

Arsenic is widely distributed in nature in air, water and soil in the form of either metalloids or chemical compounds. It is used commercially, as pesticide, wood preservative, in the manufacture of glass, paper and semiconductors. Epidemiological and clinical studies indicate that arsenic is a paradoxical human carcinogen that does not easily induce cancer in animal models. It is one of the toxic compounds known in the environment. Intermittent incidents of arsenic contamination in ground water have been reported from several parts of the world. Arsenic containing drinking water has been associated with a variety of skin and internal organ cancers. The wide human exposure to this compound through drinking water throughout the world causes great concern for human health. In the present review, we have attempted to evaluate and update the mutagenic and genotoxic effects of arsenic and its compounds based on available literature.

Animals↗

Involvement of protein kinase C-delta in DNA damage-induced apoptosis.

We have previously shown that the protein kinase C (PKC) signal transduction pathway regulates cell death by the DNA damaging agent cis-diamminedichloroplatinum(II) (cDDP). In the present study we have investigated how PKC influences the sequence of events that are triggered by cDDP-induced DNA damage. cDDP caused activation of caspases-8, -9, -3, -7 and cleavage of PKCdelta. Rottlerin, a selective inhibitor of novel PKCdelta, blocked activation of caspases, proteolytic activation of PKCdelta and cell death induced by cDDP. In contrast, Gö 6976, an inhibitor of conventional PKCalpha and betaI, did not prevent cDDP-induced caspase activation and cDDP cytotoxicity. In HeLa cells, PKCdelta was distributed both in the cytosol and heavy membrane (HM) fraction containing mitochondria. While caspase-8 was primarily cytosolic, a small amount of caspases-9, -7 and -3 could be detected in the HM fraction. cDDP caused a time-dependent increase in Cytochrome c release from the mitochondria and processing of both cytosolic and membrane-associated caspases, as well as proteolytic cleavage of PKCdelta. Rottlerin attenuated late but not early release of Cytochrome c by cDDP. It, however, inhibited activation of caspases and proteolytic cleavage of PKCdelta in both cytosolic and HM fractions. The antiapoptotic effect of rottlerin was evident when it was added together with or following cDDP addition but not when added after cDDP was removed from the medium. Thus, the PKCdelta inhibitor acts at an early stage of the cDDP-induced cell death pathway that precedes caspase activation.

Acetophenones↗

Glucose effectiveness: measurement in diabetic and nondiabetic humans.

It is well established that under the conditions of daily living, insulin secretion and insulin action determine glucose tolerance in nondiabetic humans both in the post-absorptive and post-prandial states. However, in recent years, glucose effectiveness (i.e., the ability of glucose per se to stimulate its own uptake and to suppress its own release) has also been shown to influence glucose tolerance in both diabetic and nondiabetic individuals. In states of deficient insulin action, e.g., in individuals with type 2 diabetes, glucose effectiveness assumes a greater role in determining glucose tolerance both during fasting and post-prandial conditions. A mathematical model (Minimal Model) of glucose turnover has been applied to estimate glucose effectiveness in both diabetic and nondiabetic individuals. Several investigators have demonstrated reduced glucose effectiveness in people with type 2 diabetes mellitus. However, measurements of glucose effectiveness by the traditional single compartment minimal model approach have been fraught with errors when compared to model independent estimates, especially in the diabetic population. This has led investigators to modify the parameters of the model with the incorporation of glucose tracers and the use of two-compartment model of glucose kinetics. Although this has made the indices of glucose effectiveness more robust, proper validation experiments are necessary before widespread application of these methods.

Animals↗

Electrophysiologic evidence for increased endogenous gabaergic but not glycinergic inhibitory tone in the rat spinal nerve ligation model of neuropathy.

BACKGROUND: Changes in the inhibitory activity mediated by gamma-aminobutyric acid (GABA) and glycine, acting at spinal GABAA receptors and strychnine-sensitive glycine receptors, are of interest in the development of neuropathic pain. There is anatomic evidence for changes in these transmitter systems after nerve injuries, and blocking either GABAA or glycine receptors has been shown to produce allodynia-like behavior in awake normal animals. METHODS: In this study, the possible changes in GABAergic and glycinergic inhibitory activity in the spinal nerve ligation model of neuropathic pain were studied by comparing the effects of the GABAA-receptor antagonist bicuculline and the glycine-receptor antagonist strychnine in neuropathic rats to their effects in sham-operated and nonoperated control rats. RESULTS: Bicuculline produced a dose-related facilitation of the Adelta-fiber-evoked activity in all study groups and increased C-fiber-mediated activity in the spinal nerve ligation group but not in either of the control groups. There were no differences in the effect of bicuculline on low threshold responses between the study groups. The glycine receptor antagonist strychnine did not have a statistically significant effect on any of the parameters studied in any of the control groups. CONCLUSIONS: These results support the idea of an increased GABAergic inhibitory tone in the spinal cord of neuropathic rats, possibly as compensation for increased excitability after nerve injury.

Animals↗

Systemic and regional free fatty acid metabolism in type 2 diabetes.

To determine whether type 2 diabetes mellitus alters systemic and regional free fatty acid ([3H]palmitate) metabolism, 14 nondiabetic (ND) and 14 type 2 diabetic (D) subjects underwent hyperinsulinemic-hyperglycemic (approximately 9.3 mM) clamps. The subjects were matched for age, body mass index, percent body fat, and fat-free mass. D subjects had more (P < 0.05) visceral fat than ND. During somatostatin, replacement growth hormone, and glucagon infusions, insulin was infused to achieve moderate (approximately 75 pmol/l) and high (approximately 150 pmol/l) physiological insulin levels. D subjects had greater (P < 0.02) systemic and regional (splanchnic and leg) palmitate release than ND subjects during both insulin infusion intervals. The relative contributions of splanchnic, leg, and nonsplanchnic upper body regions to systemic palmitate release did not differ between groups, although the last contributed the most (approximately 75%) to systemic palmitate release. Visceral fat area correlated with systemic palmitate flux (r = 0.45, P < 0.03) during both insulin infusions. We conclude that type 2 diabetes is associated with a generalized impairment in insulin suppression of lipolysis compared with equally obese ND individuals.

Abdomen↗

Effect of glucagon-like peptide-1(7-36)-amide on initial splanchnic glucose uptake and insulin action in humans with type 1 diabetes.

In vitro studies indicate that glucagon-like peptide-1(7-36)-amide (GLP-1) can enhance hepatic glucose uptake. To determine whether GLP-1 increases splanchnic glucose uptake in humans, we studied seven subjects with type 1 diabetes on two occasions. On both occasions, glucose was maintained at approximately 5.5 mmo/l during the night using a variable insulin infusion. On the morning of the study, a somatostatin, glucagon, and growth hormone infusion was started to maintain basal hormone levels. Glucose (containing [3H]glucose) was infused via an intraduodenal tube at a rate of 20 micromol.kg(-1).min(-1). Insulin concentrations were increased to approximately 500 pmol/l while glucose was clamped at approximately 8.8 mmol/l for the next 4 h by means of a variable intravenous glucose infusion labeled with [6,6-2H2]glucose. Surprisingly, the systemic appearance of intraduodenally infused glucose was higher (P = 0.01) during GLP-1 infusion than saline infusion, indicating a lower (P < 0.05) rate of initial splanchnic glucose uptake (1.4 +/- 1.5 vs. 4.8 +/- 0.8 micromol.kg(-1).min(-1)). On the other hand, flux through the hepatic uridine-diphosphate- glucose pool did not differ between study days (14.2 +/- 5.5 vs. 13.0 +/- 4.2 micromol.kg(-1).min(-1)), implying equivalent rates of glycogen synthesis. GLP-1 also impaired (P < 0.05) insulin-induced suppression of endogenous glucose production (6.9 +/- 2.9 vs. 1.3 +/- 1.4 micromol.kg(-1).min(-1)), but caused a time-dependent increase (P < 0.01) in glucose disappearance (93.7 +/- 10.0 vs. 69.3 +/- 6.3 micromol.kg(-1).min(-1); P < 0.01) that was evident only during the final hour of study. We conclude that in the presence of hyperglycemia, hyperinsulinemia, and enterally delivered glucose, GLP-1 increases total body but not splanchnic glucose uptake in humans with type 1 diabetes.

Blood Glucose↗

Type 2 diabetes impairs splanchnic uptake of glucose but does not alter intestinal glucose absorption during enteral glucose feeding: additional evidence for a defect in hepatic glucokinase activity.

We have previously reported that splanchnic glucose uptake, hepatic glycogen synthesis, and hepatic glucokinase activity are decreased in people with type 2 diabetes during intravenous glucose infusion. To determine whether these defects are also present during more physiological enteral glucose administration, we studied 11 diabetic and 14 nondiabetic volunteers using a combined organ catheterization-tracer infusion technique. Glucose was infused into the duodenum at a rate of 22 micromol. kg(-1). min(-1) while supplemental glucose was given intravenously to clamp glucose at approximately 10 mmol/l in both groups. Endogenous hormone secretion was inhibited with somatostatin, and insulin was infused to maintain plasma concentrations at approximately 300 pmol/l (i.e., twofold higher than our previous experiments). Total body glucose disappearance, splanchnic, and leg glucose extractions were markedly lower (P < 0.01) in the diabetic subjects than in the nondiabetic subjects. UDP-glucose flux, a measure of glycogen synthesis, was approximately 35% lower (P < 0.02) in the diabetic subjects than in the nondiabetic subjects. This was entirely accounted for by a decrease (P < 0.01) in the contribution of extracellular glucose because the contribution of the indirect pathway to hepatic glycogen synthesis was similar between groups. Neither endogenous and splanchnic glucose productions nor rates of appearance of the intraduodenally infused glucose in the portal vein differed between groups. In summary, both muscle and splanchnic glucose uptake are impaired in type 2 diabetes during enteral glucose administration. The defect in splanchnic glucose uptake appears to be due to decreased uptake of extracellular glucose, implying decreased glucokinase activity. Thus, abnormal hepatic and muscle (but not gut) glucose metabolism are likely to contribute to postprandial hyperglycemia in people with type 2 diabetes.

Absorption↗

Neuroblastoma cell lines--a versatile in vitro model in neurobiology.

Neuroblastoma (NB) cell lines are transformed, neural crest derived cells, capable of unlimited proliferation in vitro. These cell lines retain the ability of differentiation into neuronal cell types on treatment with various agents. This ability of NB cells to proliferate as well as to differentiate makes it an excellent in vitro system for various studies. This review article focuses on the applications and potential uses of murine and human NB cell lines. NB cells are extensively used for testing neurotoxicity of putative drugs such as antimalarial or anticancer agents. NB cell lines have wide applications in virus research to understand various aspects of virus-host cell interactions at the molecular and cellular levels. They have been used to dissect the relationships between proliferation, differentiation and apoptosis. This feature has been useful in understanding the pediatric cancer--neuroblastoma and for development of newer therapies.

Animal Testing Alternatives↗

Horizontal and vertical transmission of dengue virus type 2 in highly and lowly susceptible strains of Aedes aegypti mosquitoes.

Isofemale lines of Aedes aegypti mosquitoes highly and lowly susceptible to dengue type 2 (DEN-2) virus (DEN(h) and DEN(l), respectively) were established by oral feeding and individual rearing. The susceptibility at F13 generation was found to be 61% and 25% for the DEN(h) and DEN(l) line, respectively. The virus-infected mosquito females were allowed to probe on bovine albumin phosphate saline pH 7.2 (BAPS) through membrane feeders. The presence of virus in the probed BAPS was determined either by ELISA or by intrathoracic (i.t.) inoculation of mosquitoes or by both methods. The rate of oral transmission of virus was found to be 2 times higher in the DEN(h) isofemale line than in the DEN(l) one. Similarly, vertical transmission rate of the virus was found to be 7 times higher in the DEN(h) line. When batches of eggs obtained from infected female mosquitoes were allowed to hatch after two months the vertical transmission rate of the virus was very high. It is possible that, at room temperature, the virus gets an opportunity to multiply and increase its copy number in the quiescent embryos. The progeny obtained from the infected mosquitoes was found to be capable of transmitting the virus horizontally when allowed to probe on BAPS through the membrane feeder. This is the first report demonstrating horizontal transmission of DEN-2 virus by mosquitoes infected through vertical transmission. The higher vertical transmission rate of the virus in the progeny obtained from the eggs dessicated for a longer time and the horizontal transmission of the virus from the progeny is of very high epidemiological significance.

Aedes↗

Overexpression of protein kinase C-eta attenuates caspase activation and tumor necrosis factor-alpha-induced cell death.

The protein kinase C (PKC) signal transduction pathway regulates cell death by tumor necrosis factor-alpha (TNF). We previously showed that the induction of novel PKC eta isozyme by PKC activators correlated with their ability to protect MCF-7 breast cancer cells against TNF cytotoxicity. In the present study, we have transfected PKC eta in MCF-7 cells to directly examine its involvement in cell death by TNF. Overexpression of PKC eta delayed TNF-induced cell death in MCF-7 cells. TNF caused a rapid activation of caspase-8 and -7 in cells transfected with a vector. The activation of these caspases was potentiated by the PKC inhibitor bisindolylmaleimide (BIM) which downregulates PKC eta and sensitizes cells to TNF. Overexpression of PKC eta delayed the activation of caspase-8 and -7 by both TNF and the combination of BIM and TNF. These results suggest that PKC eta protects MCF-7 cells against TNF-induced cell death by preventing the activation of caspases.

Caspase 7↗

Functional features of hepatitis C virus glycoproteins for pseudotype virus entry into mammalian cells.

We have previously reported the generation of pseudotype virus from chimeric gene constructs encoding the ectodomain of the E1 or E2 glycoprotein of hepatitis C virus (HCV) genotype 1a appended to the trans membrane domain and cytoplasmic tail of the vesicular stomatitis virus (VSV) G protein. Sera derived from chimpanzees immunized with homologous HCV glycoproteins neutralized pseudotype virus infectivity (L. M. Lagging et al., J. Virol. 72, 3539-3546, 1998). We have now extended this study to further understand the role of HCV glycoproteins in pseudotype virus entry. Although a number of mammalian epithelial cells were susceptible to VSV/HCV pseudotype virus infection, plaquing efficiency was different among host cell lines. Pseudotype virus adsorption at low temperature decreased plaque numbers. Treatment of E1 or E2 pseudotype virus in media between pH 5 and 8 before adsorption on cells did not significantly reduce plaque numbers. On the other hand, treatment of cells with lysosomotropic agents or inhibitors of vacuolar H(+) ATPases had an inhibitory role on virus entry. Concanavalin A, a plant lectin, exhibited neutralization of both HCV E1 and E2 pseudotype virus infectivity. However, mannose binding protein, a C-type mammalian lectin, did not neutralize virus in the absence or presence of serum complement. Pseudotype virus infectivity was only partially inhibited by heparin, a highly sulfated glycosaminoglycan, in a saturable manner. Additional studies suggested that low-density lipoprotein receptor related molecules partially inhibit E1 pseudotype virus infectivity, while CD81 related molecules interfere with E2 pseudotype virus infectivity. A further understanding of HCV entry and strategies appropriate for mimicking cell surface molecules may help in the development of new therapeutic modalities against HCV infection.

Antigens, CD↗

Developmental toxicity of valproic acid during embryonic chick vertebral chondrogenesis.

STUDY DESIGN: Valproic acid (2-n-propylpentanoic acid, VPA), an anticonvulsant drug, was studied for its effects on cartilage matrix gene expression using dot blot hybridization with cDNA probes during early chondrogenesis in the developing lumbar spine. OBJECTIVES: To determine the noncytotoxic effects of VPA on vertebral chondrocytes at various stages of embryonic chick spine development. SUMMARY OF BACKGROUND DATA: Clinical and epidemiologic studies have indicated that maternal use of valproic acid during early pregnancy causes an increased risk for spina bifida. METHODS: The sequence of chondrogenesis in the chick lumbar region was determined for stages HH23-32 and stage-correlated with matrix gene expression by dot blot hybridization analysis using cDNA probes for type II collagen, type IX collagen, and cartilage-specific aggrecan core protein. RESULTS: The mesenchymal stage of lumbar chondrogenesis in the chick spine occurs from HH23-26, the prechondrogenic stage between HH27-28, and the chondrogenic period from HH29-32. Stabilization of the cartilage phenotype in the lumbar region is evident at HH-29. Type IX collagen and aggrecan core protein mRNA levels were significantly reduced (P < 0.01) after 48 hours of incubation of the lumbar spines from HH29-31 in the presence of 200 microg/mL and 300 microg/mL valproic acid. Lumbar spines cultured for an additional 24 hours after removal of valproic acid showed only an isolated instance of escape from the inhibitory action of 200 microg/mL valproic acid for type IX collagen at HH31. CONCLUSIONS: Valproic acid significantly alters cartilage matrix gene expression during embryonic lumbar vertebral chondrogenesis. The alteration in gene expression for critical matrix proteins during vertebral chondrogenesis may be related to mechanisms underlying the failure of neural arch development in lumbar spina bifida.

Abnormalities, Drug-Induced↗

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Animals↗

Diversity in the arrangement of the CTX prophages in classical strains of Vibrio cholerae O1.

This study reports the results of a molecular analysis of the CTX prophages in classical biotype strains of Vibrio cholerae O1 of clinical origin isolated between 1970 and 1979 in India. All strains were sensitive to group IV classical phage and polymyxin B but resistant to group 5 El Tor phage. These phenotypic traits are consistent to that exhibited by the classical biotype. PCR studies reconfirmed their biotype assignment and showed the presence of intact CTX prophages and the presence of the recently described toxin linked cryptic plasmid. Restriction fragment length polymorphism of rRNA genes and pulsed-field gel electrophoresis showed clonal diversity among the strains. The most notable observation was the finding that one strain (GP13) has three CTX prophages while another (GP147) has four CTX prophages. This is the first time heterogeneity is reported in the arrangement of the CTX prophages among classical strains of V. cholerae O1.

Bacteriophage Typing↗