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Journal articles on the topic 'HMATE1'

Author: Grafiati

Published: 4 June 2021

Last updated: 12 February 2022

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1

Ohta, Kin-ya, Katsuhisa Inoue, Tomoya Yasujima, Munenori Ishimaru, and Hiroaki Yuasa. "Functional Characteristics of Two Human MATE Transporters: Kinetics of Cimetidine Transport and Profiles of Iinhibition by Various Compounds." Journal of Pharmacy & Pharmaceutical Sciences 12, no. 3 (January 6, 2010): 388. http://dx.doi.org/10.18433/j3r59x.

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Purpose. Human multidrug and toxin extrusion protein 1 (hMATE1) and hMATE2-K are organic cation/H+ antiporters that have recently been identified and suggested to be involved in the renal brush border secretion of various organic cations. Information about functional characteristics of them has been accumulating, but still insufficient to fully understand their functions and respective roles. The present study was conducted to help clarify them. Methods. The cDNA of hMATE1 was isolated from human brain cDNA by RT-PCR and hMATE2-K cDNA was from human kidney cDNA. HEK293 cells were stably transfected with hMATE1 and hMATE2-K, and the cellular uptakes of [3H]cimetidine and [14C]tetraethylammonium (TEA) were evaluated. Results. It was first found that both hMATE1 and hMATE2-K can transport cimetidine with high affinities, indicated by small Michaelis constants of 8.00 mM and 18.18 mM, respectively. These were much smaller than those for TEA (366 mM and 375 mM, respectively, for hMATE1 and hMATE2-K). Subsequent investigation using cimetidine as a probe substrate into the profiles of inhibition of the two hMATEs by various compounds indicated that they are similar in principle but different to some extent in substrate recognition, reflecting the modest differences in amino acid sequences between them. In fact, cimetidine transport by hMATE1 was correlated to that by hMATE2-K, which is 65% similar to hMATE1, but not as good as to that by rat MATE1, which is 86% similar. Conclusions. Cimetidine was demonstrated to be a high affinity substrate of both hMATEs. Subsequent evaluation of the inhibition of hMATEs by various compounds indicated no major difference in function or role between hMATE1 and hMATE2-K.

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2

Kantauskaitė, Marta, Anna Hucke, Moritz Reike, Sara Ahmed Eltayeb, Chuyan Xiao, Vivien Barz, and Giuliano Ciarimboli. "Rapid Regulation of Human Multidrug and Extrusion Transporters hMATE1 and hMATE2K." International Journal of Molecular Sciences 21, no. 14 (July 21, 2020): 5157. http://dx.doi.org/10.3390/ijms21145157.

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Vectorial transport of organic cations (OCs) in renal proximal tubules is mediated by sequential action of human OC transporter 2 (hOCT2) and human multidrug and toxic extrusion protein 1 and 2K (hMATE1 and hMATE2K), expressed in the basolateral (hOCT2) and luminal (hMATE1 and hMATE2K) plasma membranes, respectively. It is well known that hOCT2 activity is subjected to rapid regulation by several signaling pathways, suggesting that renal OC secretion may be acutely adapted to physiological requirements. Therefore, in this work, the acute regulation of hMATEs stably expressed in human embryonic kidney cells was characterized using the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) as a marker. A specific regulation of ASP+ transport by hMATE1 and hMATE2K measured in uptake and efflux configurations was observed. In the example of hMATE1 efflux reduction by inhibition of casein kinase II, it was also shown that this regulation is able to modify transcellular transport of ASP+ in Madin–Darby canine kidney II cells expressing hOCT2 and hMATE1 on the basolateral and apical membrane domains, respectively. The activity of hMATEs can be rapidly regulated by some intracellular pathways, which sometimes are common to those found for hOCTs. Interference with these pathways may be important to regulate renal secretion of OCs.

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3

Dangprapai, Yodying, and Stephen H. Wright. "Interaction of H+ with the extracellular and intracellular aspects of hMATE1." American Journal of Physiology-Renal Physiology 301, no. 3 (September 2011): F520—F528. http://dx.doi.org/10.1152/ajprenal.00075.2011.

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Human multidrug and toxin extrusion 1 (hMATE1, SLC47A1) is a major candidate for being the molecular identity of organic cation/proton (OC/H+) exchange activity in the luminal membrane of renal proximal tubules. Although physiological function of hMATE1 supports luminal OC efflux, the kinetics of hMATE1-mediated OC transport have typically been characterized through measurement of uptake, i.e., the interaction between outward-facing hMATE1 and OCs. To examine kinetics of hMATE1-mediated transport in a more physiologically relevant direction, i.e., an interaction between inward-facing hMATE1 and cytoplasmic substrates, we measured the time course of hMATE1-mediated efflux of the prototypic MATE1 substrate, [3H]1-methyl-4-phenylpyridinium, under a variety of intra- and extracellular pH conditions, from Chinese hamster ovary cells that stably expressed the transporter. In this study, we showed that an IC50/ Ki for interaction between extracellular H+ and outward-facing hMATE1 determined from conventional uptake experiments [12.9 ± 1.23 nM (pH 7.89); n = 9] and from the efflux protocol [14.7 ± 3.45 nM (pH 7.83); n = 3] was not significantly different ( P = 0.6). Furthermore, kinetics of interaction between intracellular H+ and inward-facing hMATE1 determined using the efflux protocol revealed an IC50 for H+ of 11.5 nM (pH 7.91), consistent with symmetrical interactions of H+ with the inward-facing and outward-facing aspects of hMATE1.

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4

Yin, Jia, David J. Wagner, Bhagwat Prasad, Nina Isoherranen, Kenneth E. Thummel, and Joanne Wang. "Renal secretion of hydrochlorothiazide involves organic anion transporter 1/3, organic cation transporter 2, and multidrug and toxin extrusion protein 2-K." American Journal of Physiology-Renal Physiology 317, no. 4 (October 1, 2019): F805—F814. http://dx.doi.org/10.1152/ajprenal.00141.2019.

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Hydrochlorothiazide (HCTZ) is the most widely used thiazide diuretic for the treatment of hypertension either alone or in combination with other antihypertensives. HCTZ is mainly cleared by the kidney via tubular secretion, but the underlying molecular mechanisms are unclear. Using cells stably expressing major renal organic anion and cation transporters [human organic anion transporter 1 (hOAT1), human organic anion transporter 3 (hOAT3), human organic cation transporter 2 (hOCT2), human multidrug and toxin extrusion 1 (hMATE1), and human multidrug and toxin extrusion 2-K (hMATE2-K)], we found that HCTZ interacted with both organic cation and anion transporters. Uptake experiments further showed that HCTZ is transported by hOAT1, hOAT3, hOCT2, and hMATE2-K but not by hMATE1. Detailed kinetic analysis coupled with quantification of membrane transporter proteins by targeted proteomics revealed that HCTZ is an excellent substrate for hOAT1 and hOAT3. The apparent affinities ( Km) for hOAT1 and hOAT3 were 112 ± 8 and 134 ± 13 μM, respectively, and the calculated turnover numbers ( kcat) were 2.48 and 0.79 s−1, respectively. On the other hand, hOCT2 and hMATE2-K showed much lower affinity for HCTZ. The calculated transport efficiency ( kcat/ Km) at the single transporter level followed the rank order of hOAT1> hOAT3 > hOCT2 and hMATE2-K, suggesting a major role of organic anion transporters in tubular secretion of HCTZ. In vitro inhibition experiments further suggested that HCTZ is not a clinically relevant inhibitor for hOAT1 or hOAT3. However, strong in vivo inhibitors of hOAT1/3 may alter renal secretion of HCTZ. Together, our study elucidated the molecular mechanisms underlying renal handling of HCTZ and revealed potential pathways involved in the disposition and drug-drug interactions for this important antihypertensive drug in the kidney.

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5

Yang, Xi, Zhiyuan Ma, Sisi Zhou, Yayun Weng, Hongmei Lei, Su Zeng, Liping Li, and Huidi Jiang. "Multiple Drug Transporters Are Involved in Renal Secretion of Entecavir." Antimicrobial Agents and Chemotherapy 60, no. 10 (August 8, 2016): 6260–70. http://dx.doi.org/10.1128/aac.00986-16.

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ABSTRACTEntecavir (ETV) is a first-line antiviral agent for the treatment of chronic hepatitis B virus infection. Renal excretion is the major elimination path of ETV, in which tubular secretion plays the key role. However, the secretion mechanism has not been clarified. We speculated that renal transporters mediated the secretion of ETV. Therefore, the aim of our study was to elucidate which transporters contribute to the renal disposition of ETV. Our results revealed that ETV (50 μM) remarkably reduced the accumulation of probe substrates in MDCK cells stably expressing human multidrug and toxin efflux extrusion proteins (hMATE1/2-K), organic cation transporter 2 (hOCT2), and carnitine/organic cation transporters (hOCTNs) and increased the substrate accumulation in cells transfected with multidrug resistance-associated protein 2 (hMRP2) or multidrug resistance protein 1 (hMDR1). Moreover, ETV was proved to be a substrate of the above-described transporters. In transwell studies, the transport of ETV in MDCK-hOCT2-hMATE1 showed a distinct directionality from BL (hOCT2) to AP (hMATE1), and the cellular accumulation of ETV in cells expressing hMATE1 was dramatically lower than that of the mock-treated cells. The accumulation of ETV in mouse primary renal tubular cells was obviously affected by inhibitors of organic anion transporter 1/3 (Oat1/3), Oct2, Octn1/2, and Mrp2. Therefore, the renal uptake of ETV is likely mediated by OAT1/3 and OCT2 while the efflux is mediated by MATEs, MDR1, and MRP2, and OCTN1/2 may participate in both renal secretion and reabsorption.

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6

Kajiwara, Moto, Tomohiro Terada, Jun-ichi Asaka, Ken Ogasawara, Toshiya Katsura, Osamu Ogawa, Atsushi Fukatsu, Toshio Doi, and Ken-ichi Inui. "Critical roles of Sp1 in gene expression of human and rat H+/organic cation antiporter MATE1." American Journal of Physiology-Renal Physiology 293, no. 5 (November 2007): F1564—F1570. http://dx.doi.org/10.1152/ajprenal.00322.2007.

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A H+/organic cation antiporter (multidrug and toxin extrusion 1: MATE1/SLC47A1) plays important roles in the tubular secretion of various clinically important cationic drugs such as cimetidine. We have recently found that the regulation of this transporter greatly affects the pharmacokinetic properties of cationic drugs in vivo. No information is available about the regulatory mechanisms for the MATE1 gene. In the present study, therefore, we examined the gene regulation of human (h) and rat (r) MATE1, focusing on basal expression. A deletion analysis suggested that the regions spanning −65/−25 and −146/−38 were essential for the basal transcriptional activity of the hMATE1 and rMATE1 promoter, respectively, and that both regions contained putative Sp1-binding sites. Functional involvement of Sp1 was confirmed by Sp1 overexpression, a mutational analysis of Sp1-binding sites, mithramycin A treatment, and an electrophoretic mobility shift assay. Furthermore, we found a single nucleotide polymorphism (SNP) in the promoter region of hMATE1 (G−32A), which belongs to a Sp1-binding site. The allelic frequency of this rSNP was 3.7%, and Sp1-binding and promoter activity were significantly decreased. This is the first study to clarify the transcriptional mechanisms of the MATE1 gene and to identify a SNP affecting the promoter activity of hMATE1.

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7

Sato, Tomoko, Satohiro Masuda, Atsushi Yonezawa, Yuko Tanihara, Toshiya Katsura, and Ken-ichi Inui. "Transcellular transport of organic cations in double-transfected MDCK cells expressing human organic cation transporters hOCT1/hMATE1 and hOCT2/hMATE1." Biochemical Pharmacology 76, no. 7 (October 2008): 894–903. http://dx.doi.org/10.1016/j.bcp.2008.07.005.

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8

zhang, xiaohong, and Stephen H. Wright. "Determination of hMATE1 Turnover Rate Using Quantitative Western Analysis." FASEB Journal 34, S1 (April 2020): 1. http://dx.doi.org/10.1096/fasebj.2020.34.s1.09360.

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9

Yang, Hong, Shiwei Zhou, Dong Guo, Obinna N. Obianom, Qing Li, and Yan Shu. "Divergent Regulation of OCT and MATE Drug Transporters by Cadmium Exposure." Pharmaceutics 13, no. 4 (April 13, 2021): 537. http://dx.doi.org/10.3390/pharmaceutics13040537.

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Coordinated transcellular transport by the uptake via organic cation transporters (OCTs) in concert with the efflux via multidrug and toxin extrusion proteins (MATEs) is an essential system for hepatic and renal drug disposition. Despite their clinical importance, the regulation of OCTs and MATEs remains poorly characterized. It has been reported that cadmium (Cd2+) increase the activities of OCTs while being a substrate of MATEs. Here, we found that human (h) OCT2 protein, as compared with hMATE1, was more active in trafficking between the plasma membrane and cytoplasmic storage pool. Cd2+ exposure could significantly enhance the translocation of hOCT2 and hOCT1, but not hMATE1, to the plasma membrane. We further identified that candesartan, a widely prescribed angiotensin II receptor blocker, behaved similarly toward OCT2 and MATE1 as Cd2+ did. Importantly, Cd2+ and candesartan treatments could lead to an enhanced accumulation of metformin, which is a well-characterized substrate of OCTs/MATEs, in mouse kidney and liver, respectively. Altogether, our studies have uncovered possible divergent regulation of OCTs and MATEs by certain xenobiotics, such as Cd2+ and candesartan due to the different cellular trafficking of these two families of transporter proteins, which might significantly affect drug disposition in the liver and kidney.

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10

Matsumoto, Takuya, Takuji Kanamoto, Masato Otsuka, Hiroshi Omote, and Yoshinori Moriyama. "Role of glutamate residues in substrate recognition by human MATE1 polyspecific H+/organic cation exporter." American Journal of Physiology-Cell Physiology 294, no. 4 (April 2008): C1074—C1078. http://dx.doi.org/10.1152/ajpcell.00504.2007.

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Human multidrug and toxic compound extrusion 1 (hMATE1) is an electroneutral H+/organic cation exchanger responsible for the final excretion step of structurally unrelated toxic organic cations in kidney and liver. To elucidate the molecular basis of the substrate recognition by hMATE1, we substituted the glutamate residues Glu273, Glu278, Glu300, and Glu389, which are conserved in the transmembrane regions, for alanine or aspartate and examined the transport activities of the resulting mutant proteins using tetraethylammonium (TEA) and cimetidine as substrates after expression in human embryonic kidney 293 (HEK-293) cells. All of these mutants except Glu273Ala were fully expressed and present in the plasma membrane of the HEK-293 cells. TEA transport activity in the mutant Glu278Ala was completely absent. Both Glu300Ala and Glu389Ala and all aspartate mutants exhibited significantly decreased activity. Glu273Asp showed higher affinity for cimetidine, whereas it has reduced affinity to TEA. Glu278Asp showed decreased affinity to cimetidine. Both Glu300Asp and Glu389Asp had lowered affinity to TEA, whereas the affinity of Glu389Asp to cimetidine was fourfold higher than that of the wild-type transporter with about a fourfold decrease in Vmax value. Both Glu273Asp and Glu300Asp had altered pH dependence for TEA uptake. These results suggest that all of these glutamate residues are involved in binding and/or transport of TEA and cimetidine but that their individual roles are different.

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11

Hiasa, Miki, Takuya Matsumoto, Toshinori Komatsu, and Yoshinori Moriyama. "Wide variety of locations for rodent MATE1, a transporter protein that mediates the final excretion step for toxic organic cations." American Journal of Physiology-Cell Physiology 291, no. 4 (October 2006): C678—C686. http://dx.doi.org/10.1152/ajpcell.00090.2006.

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MATE1 was the first mammalian example of the multidrug and toxin extrusion (MATE) protein family to be identified. Human MATE1 (hMATE1) is predominantly expressed and localized to the luminal membranes of the urinary tubules and bile canaliculi and mediates H+-coupled electroneutral excretion of toxic organic cations (OCs) into urine and bile (Otsuka M, Matsumoto T, Morimoto R, Arioka S, Omote H, and Moriyama Y. Proc Natl Acad Sci USA 102: 17923–17928, 2005). mMATE1, a mouse MATE ortholog, is also predominantly expressed in kidney and liver, although its transport properties are not yet characterized. In the present study, we investigated the transport properties and localization of mMATE1. Upon expression of this protein in HEK-293 cells, mMATE1 mediated electroneutral H+/tetraethylammonium exchange and showed a substrate specificity similar to that of hMATE1. Immunological techniques with specific antibodies against mMATE1 combined with RT-PCR revealed that mMATE1 is also expressed in various cells, including brain glia-like cells and capillaries, pancreatic duct cells, urinary bladder epithelium, adrenal gland cortex, α cells of the islets of Langerhans, Leydig cells, and vitamin A-storing Ito cells. These results indicate that mMATE1 is a polyspecific H+/OC exchanger. The unexpectedly wide distribution of mMATE1 suggests involvement of this transporter protein in diverse biological functions other than excretion of OCs from the body.

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12

Chen, Ying, Kristen Teranishi, Shuanglian Li, Sook Wah Yee, Stephanie Hesselson, Doug Stryke, Susan J. Johns, Thomas E. Ferrin, Pui Kwok, and Kathleen M. Giacomini. "Genetic variants in multidrug and toxic compound extrusion-1, hMATE1, alter transport function." Pharmacogenomics Journal 9, no. 2 (January 27, 2009): 127–36. http://dx.doi.org/10.1038/tpj.2008.19.

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13

Shinya, Susumu, Kentaro Kawai, Atsushi Tarui, Yukiko Karuo, Kazuyuki Sato, Masaya Matsuda, Kazuyuki Kitatani, et al. "Importance of the Azole Moiety of Cimetidine Derivatives for the Inhibition of Human Multidrug and Toxin Extrusion Transporter 1 (hMATE1)." Chemical and Pharmaceutical Bulletin 69, no. 9 (September 1, 2021): 905–12. http://dx.doi.org/10.1248/cpb.c21-00429.

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14

Yin, Jia, Haichuan Duan, and Joanne Wang. "Impact of Substrate-Dependent Inhibition on Renal Organic Cation Transporters hOCT2 and hMATE1/2-K-Mediated Drug Transport and Intracellular Accumulation." Journal of Pharmacology and Experimental Therapeutics 359, no. 3 (October 6, 2016): 401–10. http://dx.doi.org/10.1124/jpet.116.236158.

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15

Ogawa, R., T. Mikami, M. Takahashi, and H. Echizen. "PP137—Effects of the genetic polymorphisms of human multidrug and toxin extrusion 1 (HMATE1/SLC47A1) transporter on the renal tubular secretion of N1-methylnicotinamide." Clinical Therapeutics 35, no. 8 (August 2013): e58-e59. http://dx.doi.org/10.1016/j.clinthera.2013.07.159.

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16

Xue, Weiwei, Tingting Fu, Guoxun Zheng, Gao Tu, Yang Zhang, Fengyuan Yang, Lin Tao, Lixia Yao, and Feng Zhu. "Recent Advances and Challenges of the Drugs Acting on Monoamine Transporters." Current Medicinal Chemistry 27, no. 23 (July 1, 2020): 3830–76. http://dx.doi.org/10.2174/0929867325666181009123218.

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Background: The human Monoamine Transporters (hMATs), primarily including hSERT, hNET and hDAT, are important targets for the treatment of depression and other behavioral disorders with more than the availability of 30 approved drugs. Objective: This paper is to review the recent progress in the binding mode and inhibitory mechanism of hMATs inhibitors with the central or allosteric binding sites, for the benefit of future hMATs inhibitor design and discovery. The Structure-Activity Relationship (SAR) and the selectivity for hit/lead compounds to hMATs that are evaluated by in vitro and in vivo experiments will be highlighted. Methods: PubMed and Web of Science databases were searched for protein-ligand interaction, novel inhibitors design and synthesis studies related to hMATs. Results: Literature data indicate that since the first crystal structure determinations of the homologous bacterial Leucine Transporter (LeuT) complexed with clomipramine, a sizable database of over 100 experimental structures or computational models has been accumulated that now defines a substantial degree of structural variability hMATs-ligands recognition. In the meanwhile, a number of novel hMATs inhibitors have been discovered by medicinal chemistry with significant help from computational models. Conclusion: The reported new compounds act on hMATs as well as the structures of the transporters complexed with diverse ligands by either experiment or computational modeling have shed light on the poly-pharmacology, multimodal and allosteric regulation of the drugs to transporters. All of the studies will greatly promote the Structure-Based Drug Design (SBDD) of structurally novel scaffolds with high activity and selectivity for hMATs.

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17

Deng, Yuehua, and Yani Li. "Surface-Bound Humic Acid Increased Propranolol Sorption on Fe3O4/Attapulgite Magnetic Nanoparticles." Nanomaterials 10, no. 2 (January 24, 2020): 205. http://dx.doi.org/10.3390/nano10020205.

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This study explored the feasibility of utilizing a novel sorbent humic acid (HA) coated Fe3O4/attapulgite (MATP) magnetic nanoparticles (HMATP) for the sorption of propranolol from aqueous solutions. MATP and bare Fe3O4 nanoparticles were also synthesized under similar preparation conditions. The FTIR, Zeta potential, XRD, VSM, TEM, and TGA analyses were conducted to characterize the sorbent materials. The effects of pH, sorbent dosage, ionic strength, HA in the aqueous solution, contact time and initial sorbate concentration on sorption of propranolol were investigated using batch sorption experiments. The results suggested that the sorption capacity of HMATP showed little change from pH 4 to 10. Na+ and Ca2+ slightly inhibited the sorption of propranolol on HMATP. While HA in solution enhanced both MATP and HMATP, which indicated that HMATP can resist HA interference in water. Further, the less leaching amounts of Fe and HA suggested a good stability of HMATP. In all conditions, sorption capacity of propranolol on HMATP was obviously higher than that on MATP, which indicated that surface-coated HA played an important role in the propranolol sorption process. Electrostatic interaction, cation exchange, hydrogen bonding, and π–π electron donor acceptor interactions were considered as the sorption mechanisms.

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Hoyer, Joachim, Meike Kuehn, Christiane Degenhardt, Norbert Runkel, Martin Paul, MC Benjamin Franklin, and Ralf Koehler. "Expression of Ryanodine Receptor 3 and Trp Channels in Endothelium of Human Mesenteric Artery: A Single-Cell Rt-Pcr and Patch-Clamp Analysis in Situ ." Hypertension 36, suppl_1 (October 2000): 719. http://dx.doi.org/10.1161/hyp.36.suppl_1.719-d.

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P146 Ca 2+ mobilization plays an important role in endothelial function by stimulating Ca 2+ -dependent synthesis of vasodilating factors. In addition to InsP 3 - mediated Ca 2+ store depletion, Ca 2+ release from ryanodine-sensitive pools and Ca 2+ -influx through cation channels of the TRP-gene family have been suggested to be involved in endothelial Ca 2+ signaling. In cultured endothelial cells (EC) the function and expression of ryanodine-receptors (RyR) and TRP channels might differ substantially from those in native endothelium of human blood vessels. We, therefore, characterized expression and function of RyR and TRP channels in EC of small human mesenteric artery (MA) by use of single-cell RT-PCR and patch-clamp techniques in situ. MA were isolated from colon specimens of patients subjected to hemicolectomy. For single-cell RT-PCR and PC experiments single human mesenteric artery EC (HMAEC) were harvested directly from the luminal vessel with the patch pipette. Expression of the RyR subtype 3, but not of the RyR1 and RyR2 subtpyes was detected in 25% of HMAEC samples. Correspondingly, in PC experiments in HMAEC, application of caffeine (0.5 mM) induced Ca 2+ -release from ryanodine-sensitive stores and subsequently activation of Ca 2+ -activated K + channels leading to a sustained endothelial hyperpolarization from a resting potential of 28 ± 3 mV to -46 ± 4 mV. Single HMAEC expressed the TRP subtypes, TRP1 and TRP3, but not TRP 4 and 6. The TRP1 was the predominantly expressed TRP subtype as expression was detected in 16% of HMAEC. TRP3 expression was detected in only 3% of HMAEC. In single-channel and whole-cell patch clamp experiments in HMAEC, InsP 3 -mediated Ca 2+ -store depletion in response to bradykinin (100 nM) activated TRP related nonselective cation currents leading to Ca 2+ entry. In conclusion, Ca 2+ release from ryanodine-sensitive stores mediated by RyR3 and Ca 2+ entry through TRP1 might represent important components of endothelial Ca 2+ signaling and thereby of endothelial function in intact human blood vessels.

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Law, Brian J. C., Anna-Winona Struck, Matthew R. Bennett, Barrie Wilkinson, and Jason Micklefield. "Site-specific bioalkylation of rapamycin by the RapM 16-O-methyltransferase." Chemical Science 6, no. 5 (2015): 2885–92. http://dx.doi.org/10.1039/c5sc00164a.

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Characterisation of a rapamycin O-methyltransferase (RapM) and its utilisation in coupled reactions, with an improved variant of the human methionine adenosyl transferase (hMAT2A), results in new regioselectively alkylated rapamycin derivatives.

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hmamed_abdelaziz,F.Tadeo, Chakir_elkasri,. "C. El-Kasri, A. Hmamed, E. H. Tissir." International Journal of Computer Applications 44, no. 18 (April 30, 2012): 13–21. http://dx.doi.org/10.5120/6362-7604.

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21

Zeng, Ping, Jing Dai, Siyi Jin, and Xiang Zhou. "Aggregating multiple expression prediction models improves the power of transcriptome-wide association studies." Human Molecular Genetics 30, no. 10 (February 22, 2021): 939–51. http://dx.doi.org/10.1093/hmg/ddab056.

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Abstract Transcriptome-wide association study (TWAS) is an important integrative method for identifying genes that are causally associated with phenotypes. A key step of TWAS involves the construction of expression prediction models for every gene in turn using its cis-SNPs as predictors. Different TWAS methods rely on different models for gene expression prediction, and each such model makes a distinct modeling assumption that is often suitable for a particular genetic architecture underlying expression. However, the genetic architectures underlying gene expression vary across genes throughout the transcriptome. Consequently, different TWAS methods may be beneficial in detecting genes with distinct genetic architectures. Here, we develop a new method, HMAT, which aggregates TWAS association evidence obtained across multiple gene expression prediction models by leveraging the harmonic mean P-value combination strategy. Because each expression prediction model is suited to capture a particular genetic architecture, aggregating TWAS associations across prediction models as in HMAT improves accurate expression prediction and enables subsequent powerful TWAS analysis across the transcriptome. A key feature of HMAT is its ability to accommodate the correlations among different TWAS test statistics and produce calibrated P-values after aggregation. Through numerical simulations, we illustrated the advantage of HMAT over commonly used TWAS methods as well as ad hoc P-value combination rules such as Fisher’s method. We also applied HMAT to analyze summary statistics of nine common diseases. In the real data applications, HMAT was on average 30.6% more powerful compared to the next best method, detecting many new disease-associated genes that were otherwise not identified by existing TWAS approaches. In conclusion, HMAT represents a flexible and powerful TWAS method that enjoys robust performance across a range of genetic architectures underlying gene expression.

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22

Korostenski, Jiri. "Cognitive aspects of touch as a source of linguistic reflection." XLinguae 10, no. 2 (April 2017): 125–33. http://dx.doi.org/10.18355/xl.2017.10.02.11.

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23

Joyner, D. E., T. A. Damron, A. Aboulafia, W. Bokor, J. D. Bastar, and R. L. Randall. "Heterogeneous expression of melanoma antigen (hMAGE) mRNA in mesenchymal neoplasia." Tissue Antigens 68, no. 1 (July 2006): 19–27. http://dx.doi.org/10.1111/j.1399-0039.2006.00618.x.

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24

Ouyang, Wei, Guo Feng Yu, and Fang Fang Zhu. "Research on Anti-Rutting Performance of High Modulus Asphalt Concrete Pavement." Advanced Materials Research 163-167 (December 2010): 4474–77. http://dx.doi.org/10.4028/www.scientific.net/amr.163-167.4474.

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The new ways of anti-rutting was put forward by improving modulus of asphalt concrete and the effect of HMAT(high modulus asphalt concrete) on rutting is studied in view of mechanics; The cause of asphalt pavement track is closely related to pavement structure under load. Starting from the mechanism of rutting, the mechanical property of HMAT and the effect of modulus in middle layer on the rutting were analyzed; the dynamic stability and modulus of HMAC were analyzed by text and the result show that Increase of the dynamic stability and modulus of HMAC went against rutting; The mechanism of pavement structure was analyzed by the numerical analysis show that the maximum shear stress occurred in middle layer of pavement structure according to mechanical calculation. HMAC can raise modulus of elasticity of middle layer. HMAC can also improve stress state of pavement structure, reduce shear strain and prevent asphalt pavement track.

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Liang, J., F. Liu, J. Zou, H. H. K. Xu, Q. Han, Z. Wang, B. Li, et al. "pH-Responsive Antibacterial Resin Adhesives for Secondary Caries Inhibition." Journal of Dental Research 99, no. 12 (June 29, 2020): 1368–76. http://dx.doi.org/10.1177/0022034520936639.

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Secondary caries caused by dental plaque is one of the major reasons for the high failure rate of resin composite restoration. Although antimicrobial agent–modified dental restoration systems have been researched for years, few reported intelligent anticaries materials could respond to the change of the oral environment and help keep oral eubiosis. Herein, we report tertiary amine (TA)–modified resin adhesives (TA@RAs) with pH-responsive antibacterial effect to reduce the occurrence of secondary caries. Two kinds of newly designed TA monomers were synthesized: DMAEM (dodecylmethylaminoethyl methacrylate) and HMAEM (hexadecylmethylaminoethyl methacrylate). In the minimum inhibitory concentration and minimum bactericidal concentration test against Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii, they exhibited antibacterial effect only in acidic medium, which preliminarily verified the acid-activated effect of TAs. Then DMAEM and HMAEM were incorporated into adhesive resin at the mass fraction of 5%, yielding TA@RAs. In vivo and in vitro tests showed that the mechanical properties and biocompatibility of the adhesive were not affected. A S. mutans biofilm model in acidic and neutral medium was used and confirmed that TA@RAs could respond to the critical pH value of de-/remineralization and acquire reversible antibiofilm effect via the protonation and deprotonation of TAs. Meanwhile, the stability of antibacterial effect was confirmed via a 5-d pH-cycling experiment and a saliva-derived biofilm aging model. Furthermore, 16S rRNA gene sequencing showed that TA@RAs could increase the diversity of the saliva-derived biofilms, which implied that the novel materials could help regulate the microbial community to a healthy one. Finally, an in vitro demineralization model and in vivo secondary caries model were applied and demonstrated that TA@RAs could prevent secondary dental caries effectively. In summary, the reversible pH-responsive and non–drug release antibacterial resin adhesives ingeniously overcome the defect of the present materials and hold great promise for clinical application.

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Et al., Ngoc Hai Tran. "Information and Communication Technology application inpre-service teacher training programs in Vietnamese universities." Psychology and Education Journal 58, no. 1 (January 29, 2021): 895–910. http://dx.doi.org/10.17762/pae.v58i1.841.

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This study investigated how information and communication technologies are beingappliedinteachereducationprogramsinthreeuniversities including Tay Nguyen University, Ha Tinh University and Vinh UniversityinVietnam.Aquestionnaire handfacultybrochureswereusedtocollectdatafromfinalyearpre-service hteachers hinthose institutions hin hVietnam, hwhich hwere hpurposefullyselected.Thefindings hrevealed hthat hthe hthree hhigher heducation hinstitutions hare hnot hexposingpre-service hteachers hto hthe hculture hof he-learning; hpre-service hteachers hand heducational htechnologyteacher-educators hdo hnot hengage hin hreciprocal hintergenerational hmentoring; hdocument hanalysisrevealed hthat heducational htechnology hcourses hdoes hnot hcontain hadequate hICT-based hcontents handactivities; hand hthat heducation hmethod hcourses hdo hnot hinvolve hthe huse hof hICT-based htools hfordesigning hand hcreating hICT-based hactivities. hBased hon hthese hfindings, aaa number of recommendations hwere hmade to improve the ICT application in higher education institutions in Vietnam.

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Salter, B. J., V. Sarkar, L. Huang, P. Rassiah, H. Zhao, J. Huang, M. Szegedi, and D. K. Gaffney. "Hybrid Modulated Arc Therapy (HMAT) on an Artiste Linac." International Journal of Radiation Oncology*Biology*Physics 90, no. 1 (September 2014): S941. http://dx.doi.org/10.1016/j.ijrobp.2014.05.2660.

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XU, DAOYI. "Counter-example to a recent result on the decay rate for stable linear delay systems by A. Hmamed." International Journal of Control 44, no. 6 (December 1986): 1779–80. http://dx.doi.org/10.1080/00207178608933703.

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29

Hwang, Soo-in, Wen-Lin Kuo, Joanne F. Cochran, Raphael C. Guzman, Tetsuya Tsukamoto, Gautam Bandyopadhyay, Ken Myambo, and Colin C. Collins. "Assignment of HMAT1, the Human Homolog of the Murine Mammary Transforming Gene (MAT1) Associated with Tumorigenesis, to 1q21.1, a Region Frequently Gained in Human Breast Cancers." Genomics 42, no. 3 (June 1997): 540–42. http://dx.doi.org/10.1006/geno.1997.4768.

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30

Nomoto, Shuji, Nobuhiro Haruki, Takao Takahashi, Akira Masuda, Takashi Koshikawa, Toshitada Takahashi, Yoshitaka Fujii, Hirotaka Osada, and Takashi Takahashi. "Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers." Oncogene 18, no. 50 (November 1999): 7180–83. http://dx.doi.org/10.1038/sj.onc.1203141.

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31

Graillot, A., S. Djenadi, C. Faur, D. Bouyer, S. Monge, and J. J. Robin. "Removal of metal ions from aqueous effluents involving new thermosensitive polymeric sorbent." Water Science and Technology 67, no. 6 (March 1, 2013): 1181–87. http://dx.doi.org/10.2166/wst.2013.671.

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In this work, new thermosensitive copolymers bearing phosphonated groups were synthesized and used to remove metal pollution. Sorption properties are brought by hydrolyzed (dimethoxyphosphoryl)methyl 2-methylacrylate (hMAPC1) monomer. N-n-propylacrylamide (NnPAAm) led to the thermoresponsive properties of the copolymers. Low lower critical solution temperature (LCST) values were observed, ranging between 20 and 25 °C depending on the molar ratio of each monomer in the copolymer. Sorption properties of these copolymers towards nickel ions were evaluated for increasing temperatures (10–40 °C), Ni ion concentrations of 20 mg L−1 and pH values between 3 and 7. Best results were observed for temperatures just lower than the LCST (20 °C), when the copolymer was fully soluble in water solution. For temperature higher than the LCST, phosphonic diacid groups accessibility was considerably reduced by the precipitation of the thermosensitive part of the copolymer leading to lower sorption properties. In these conditions, the highest Ni removal by the copolymer was observed for pH = 7, when there was almost no competition between the sorption of H+ and Ni2+ ions on the phosphonic acid groups. These optimal conditions enabled removal of about 70% of the nickel in the synthetic effluent.

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32

Starheim, Kristian K., Darina Gromyko, Rune Evjenth, Anita Ryningen, Jan Erik Varhaug, Johan R. Lillehaug, and Thomas Arnesen. "Knockdown of Human Nα-Terminal Acetyltransferase Complex C Leads to p53-Dependent Apoptosis and Aberrant Human Arl8b Localization." Molecular and Cellular Biology 29, no. 13 (April 27, 2009): 3569–81. http://dx.doi.org/10.1128/mcb.01909-08.

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ABSTRACT Protein Nα-terminal acetylation is one of the most common protein modifications in eukaryotic cells. In yeast, three major complexes, NatA, NatB, and NatC, catalyze nearly all N-terminal acetylation, acetylating specific subsets of protein N termini. In human cells, only the NatA and NatB complexes have been described. We here identify and characterize the human NatC (hNatC) complex, containing the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31. This complex associates with ribosomes, and hMak3 acetylates Met-Leu protein N termini in vitro, suggesting a model in which the human NatC complex functions in cotranslational N-terminal acetylation. Small interfering RNA-mediated knockdown of NatC subunits results in p53-dependent cell death and reduced growth of human cell lines. As a consequence of hMAK3 knockdown, p53 is stabilized and phosphorylated and there is a significant transcriptional activation of proapoptotic genes downstream of p53. Knockdown of hMAK3 alters the subcellular localization of the Arf-like GTPase hArl8b, supporting that hArl8b is a hMak3 substrate in vivo. Taken together, hNatC-mediated N-terminal acetylation is important for maintenance of protein function and cell viability in human cells.

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33

Voff, I. "About fallopian tube cysts." Journal of obstetrics and women's diseases 5, no. 5 (August 7, 2020): 491–500. http://dx.doi.org/10.17816/jowd55491-500.

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Already with a microscopic examination of the cut out bristles of the fallopian tubes, we notice that sometimes the mucous membrane is more changed, another muscle or only the peritoneal cover, sometimes all three layers of it are equally changed; The contents of these brushes are also very diverse, which is transparent like water and poor lumps, serous with an abundant amount of lumps, stained with blood, pure bloody, in various degrees of suppuration or decomposition, liquid or thick, curdled lime or sedimentary. Because of these data, it is impossible to describe all these conditions under one common name "cysts of fallopian tubes" and it has long been customary by the nature of the contents to divide these cysts into hydro, -hmato- and pyosalpinx; but even such a definition is not enough, since it does not indicate either the ethology or the pathological anatomy of these changes, therefore, when describing these brushes, attention should be paid to both the reasons for the formation of various accumulations of fluid, as well as the mechanism of formation of these brushes, stnkakh pipes and their pathological and anatomical consequences.

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34

Grimaldo-Pantoja, Graciela L., Genhua Niu, Youping Sun, Arturo Castro-Rocha, Emilio Álvarez-Parrilla, Juan P. Flores-Márgez, Baltazar Corral-Díaz, and Pedro Osuna-Ávila. "EFECTO NEGATIVO DEL RIEGO SALINO EN COMPONENTES DEL RENDIMIENTO Y FITOQUÍMICOS DE CHILE (Capsicum annuum) INOCULADO CON HONGOS MICORRÍCICOS ARBUSCULARES." Revista Fitotecnia Mexicana 40, no. 2 (June 20, 2017): 141–49. http://dx.doi.org/10.35196/rfm.2017.2.141-149.

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Se evaluó el efecto de dos consorcios de hongos micorrícicos arbusculares (HMA) aislados de plantas de huizache (Acacia sp.) (HMA1) y de una asociación entre Larrea tridentata y Opuntia sp. (HMA2), nativas del desierto Chihuahuense, en los componentes del rendimiento y fitoquímicos en plantas de chile Jalapeño var. M crecidas bajo estrés salino en condiciones de invernadero. El diseño experimental constó de dos factores: HMA (HMA-, HMA1 y HMA2), y salinidad (testigo, 4 y 8 dS m-1) de una solución de NaCl y CaCl2, con nueve repeticiones por tratamiento. El número de esporas fue contabilizado y las plantas se inocularon con 40,000 esporas. La solución salina se aplicó 30 d después de la inoculación durante ocho semanas. El fósforo se aplicó con una solución de 44 mg L-1 de KH2PO4 a las plantas sin inocular y de 22 mg L-1 a las plantas inoculadas. La micorrización al final del experimento osciló entre 22 y 32 % en las plantas inoculadas. La salinidad afectó significativamente el desarrollo y el verdor de las plantas. Aunque el factor HMA tuvo un efecto negativo en el número de frutos, no se afectó el rendimiento en el peso fresco de los frutos. La salinidad tuvo un efecto negativo en el peso fresco de los frutos. Los HMA incrementaron significativamente el contenido de fósforo y ácido ascórbico, sin verse afectados el desarrollo y fisiología de la planta a pesar de la reducción en la cantidad de fósforo exógeno aplicado. La concentración de fósforo en los frutos fue mayor en las plantas inoculadas con HMA2. A mayor salinidad, los frutos tuvieron menor concentración de ácido ascórbico pero mayor concentración de fenoles totales en los frutos. El contenido de capsaicinoides no fue afectado por ninguno de los factores estudiados.

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35

Falatehan, A. Faroby, and Adrianus Dwi Siswanto. "Nilai Ekonomi Penegakkan Disiplin Lalu Lintas Di Lampu Merah Bubulak, Kota Bogor Terhadap Pendapatan Daerah (Benchmarking Kasus Di Malaysia)." Warta Penelitian Perhubungan 24, no. 1 (May 9, 2019): 59. http://dx.doi.org/10.25104/warlit.v24i1.984.

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ABSTRACTTraffic violations is still not taken seriously in Indonesia, 111~for hmately gafe a big impact 011 regional income. This study discused about the impact tl1e implementation of traffic discipline on local income based on Law No. 21 of 2009. This study approaches the number of violations associated witli the penalties for violations. Observations was conducted in the morning, afternoon and evening for 2 hours which is a solid hour passengers. While the observations made to the vehicle who commits an offense within that period. Further estimated the average per day of violation for the incident and then calculated the amount of the fine revenue in certain periods. The results of the study found that the estimate of receipts relatively large fines which indicates the first violation ever occurred that indicate the presence of non-compliance of traffic regulations. The second penalty is the appropriate option to create a deterrent effect on the offense. Fines provide benefits to local government as a source of income as well as educate tire publictransportation drivers to obey the rules. In Malaysia, a fine policy can be effective because the workers are very disciplined and a beingof the rules. On the other hand it is designed with a simple mechanism in which fines violators will pay the fine at the time of extending the driver's license. This approach is effective for improving adherence offenders while keeping the fine revenue obviously go into the treasuryaccount.Key Words: traffic violations, discipline, Law No. 21 of 2009, revenues

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36

Boutigny, Sylvain, Emeline Sautron, Giovanni Finazzi, Corinne Rivasseau, Annie Frelet-Barrand, Marinus Pilon, Norbert Rolland, and Daphné Seigneurin-Berny. "HMA1 and PAA1, two chloroplast-envelope PIB-ATPases, play distinct roles in chloroplast copper homeostasis." Journal of Experimental Botany 65, no. 6 (February 7, 2014): 1529–40. http://dx.doi.org/10.1093/jxb/eru020.

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37

Chamizo-Ampudia, Alejandro, Aurora Galvan, Emilio Fernandez, and Angel Llamas. "The Chlamydomonas reinhardtii Molybdenum Cofactor Enzyme crARC Has a Zn-Dependent Activity and Protein Partners Similar to Those of Its Human Homologue." Eukaryotic Cell 10, no. 10 (July 29, 2011): 1270–82. http://dx.doi.org/10.1128/ec.05096-11.

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ABSTRACT The ARC (amidoxime reducing component) proteins are molybdenum cofactor (Moco) enzymes named hmARC1 and hmARC2 (human ARCs [hmARCs]) in humans and YcbX in Escherichia coli. They catalyze the reduction of a broad range of N-hydroxylated compounds (NHC) using reducing power supplied by other proteins. Some NHC are prodrugs or toxic compounds. YcbX contains a ferredoxin (Fd) domain and requires the NADPH flavin reductase CysJ to reduce NHC. In contrast, hmARCs lack the Fd domain and require a human cytochrome b5 (hCyt b5 ) and a human NADH Cyt b5 reductase (hCyt b5- R) to reduce NHC. The ARC proteins in the plant kingdom are uncharacterized. We demonstrate that Chlamydomonas reinhardtii mutants defective in Moco biosynthesis genes are sensitive to the NHC N 6 -hydroxylaminopurine (HAP). The Chlamydomonas reinhardtii ARC protein crARC has been purified and characterized. The six Chlamydomonas Fds were isolated, but none of them are required by crARC to reduce HAP. We have also purified and characterized five C. reinhardtii Cyt b5 (crCyt b5 ) and two flavin reductases, one that is NADPH dependent (crCysJ) and one that is NADH dependent (crCyt b5 -R). The data show that crARC uses crCyt b5 - 1 and crCyt b5 -R to reduce HAP. The crARC has a Zn-dependent activity, and the presence of Zn increases its V max more than 14-fold. In addition, all five cysteines of crARC were substituted by alanine, and we demonstrate that the fully conserved cysteine 252 is essential for both Moco binding and catalysis. Therefore, it is proposed that crARC belongs to the sulfite oxidase family of Moco enzymes.

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38

Rugmini Ammal, P., M. Prajila, and Abraham Joseph. "Physicochemical studies on the inhibitive properties of a 1,2,4-triazole Schiff’s base, HMATD, on the corrosion of mild steel in hydrochloric acid." Egyptian Journal of Petroleum 27, no. 3 (September 2018): 307–17. http://dx.doi.org/10.1016/j.ejpe.2017.05.002.

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39

Ramya, K., and Abraham Joseph. "Dependence of temperature on the corrosion protection properties of vanillin and its derivative, HMATD, towards copper in nitric acid: theoretical and electroanalytical studies." Research on Chemical Intermediates 41, no. 2 (June 5, 2013): 1053–77. http://dx.doi.org/10.1007/s11164-013-1254-5.

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40

Camp, Claire L., Eslam M. Moustafa, Helen J. Reid, Barry L. Sharp, and Tamer Shoeib. "An ICP-MS, ESI-MS and molecular modelling investigation of homogeneous gallium affinity tagging (HMAT) of phosphopeptides." International Journal of Mass Spectrometry 341-342 (May 2013): 18–27. http://dx.doi.org/10.1016/j.ijms.2013.03.007.

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41

Parshall, Karen V. H. "Note from the managing editor." Historia Mathematica 22, no. 3 (1995): 225. http://dx.doi.org/10.1006/hmat.1995.1023.

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42

Hedman, Bruce A. "An Earlier Date for “Cramer's Rule”." Historia Mathematica 26, no. 4 (November 1999): 365–68. http://dx.doi.org/10.1006/hmat.1999.2247.

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43

Zitarelli, David E. "ABSTRACTS." Historia Mathematica 26, no. 3 (August 1999): 295–308. http://dx.doi.org/10.1006/hmat.1999.2248.

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44

Gupta, R. C. "Indian doctoral theses in the field of history of mathematics." Historia Mathematica 20, no. 3 (August 1993): 310–14. http://dx.doi.org/10.1006/hmat.1993.1027.

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45

Silva, Clóvis Pereira Da. "The research group on history of mathematics at the Federal University of Paraná." Historia Mathematica 20, no. 3 (August 1993): 318–19. http://dx.doi.org/10.1006/hmat.1993.1028.

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46

Rowe, David E. "Revolutions in mathematics." Historia Mathematica 20, no. 3 (August 1993): 320–23. http://dx.doi.org/10.1006/hmat.1993.1029.

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47

Ferreirós, José. "On the relations between Georg Cantor and Richard Dedekind." Historia Mathematica 20, no. 4 (November 1993): 343–63. http://dx.doi.org/10.1006/hmat.1993.1030.

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48

Rider, Robin E. "Reviews." Historia Mathematica 21, no. 1 (February 1994): 95–96. http://dx.doi.org/10.1006/hmat.1994.1012.

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49

Meskens, Ad. "Wine gauging in late 16th- and early 17th-century antwerp." Historia Mathematica 21, no. 2 (May 1994): 121–47. http://dx.doi.org/10.1006/hmat.1994.1013.

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50

Erlichson, Herman. "The visualization of quadratures in the mystery of corollary 3 to proposition 41 of Newton's Principia." Historia Mathematica 21, no. 2 (May 1994): 148–61. http://dx.doi.org/10.1006/hmat.1994.1014.

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