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Article: Physiological Appetite Regulation and Bariatric Surgery.

Ramasamy, Indra

2024 Volume 13, Issue 5

Abstract: Obesity remains a common metabolic disorder and a threat to health as it is associated with numerous complications. Lifestyle modifications and caloric restriction can achieve limited weight loss. Bariatric surgery is an effective way of achieving ... ...

Abstract	Obesity remains a common metabolic disorder and a threat to health as it is associated with numerous complications. Lifestyle modifications and caloric restriction can achieve limited weight loss. Bariatric surgery is an effective way of achieving substantial weight loss as well as glycemic control secondary to weight-related type 2 diabetes mellitus. It has been suggested that an anorexigenic gut hormone response following bariatric surgery contributes to weight loss. Understanding the changes in gut hormones and their contribution to weight loss physiology can lead to new therapeutic treatments for weight loss. Two distinct types of neurons in the arcuate hypothalamic nuclei control food intake: proopiomelanocortin neurons activated by the anorexigenic (satiety) hormones and neurons activated by the orexigenic peptides that release neuropeptide Y and agouti-related peptide (hunger centre). The arcuate nucleus of the hypothalamus integrates hormonal inputs from the gut and adipose tissue (the anorexigenic hormones cholecystokinin, polypeptide YY, glucagon-like peptide-1, oxyntomodulin, leptin, and others) and orexigeneic peptides (ghrelin). Replicating the endocrine response to bariatric surgery through pharmacological mimicry holds promise for medical treatment. Obesity has genetic and environmental factors. New advances in genetic testing have identified both monogenic and polygenic obesity-related genes. Understanding the function of genes contributing to obesity will increase insights into the biology of obesity. This review includes the physiology of appetite control, the influence of genetics on obesity, and the changes that occur following bariatric surgery. This has the potential to lead to the development of more subtle, individualised, treatments for obesity.
Language	English
Publishing date	2024-02-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13051347
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Article: A Single Center Study Investigating Clinical Outcomes of Testing for Multiple Myeloma and Immune Deficiency at Low Globulin Levels.

Ramasamy, Indra

Journal of blood medicine

2023 Volume 14, Page(s) 345–358

Abstract: Background: Both primary (e.g. common variable immune deficiency, CVID) and secondary immune deficiency as well as multiple myeloma (MM) require medical intervention and treatment delay can exacerbate morbidity. This study investigated the potential ... ...

Abstract	Background: Both primary (e.g. common variable immune deficiency, CVID) and secondary immune deficiency as well as multiple myeloma (MM) require medical intervention and treatment delay can exacerbate morbidity. This study investigated the potential importance of low levels of calculated globulin to detect immune deficiency and MM associated with immunoparesis (light chain, non-secretory MM). Methods: One hundred and thirty-nine patient serum samples from community physicians and outpatient clinics for liver function tests with low calculated globulin (<16 g/L, RR 18-37 g/L) levels were screened for immunoglobulins and protein electrophoresis. Further, 110 patients with globulin levels ≤16 g/L with screening for immunoglobulin levels and protein electrophoresis, requested through routine clinical care, were included in the analysis. Results: Approximately 47% of patients in this cohort had secondary antibody deficiency as a result of hematological malignancy. Secondary iatrogenic (immunosuppressants, antiepileptic drugs) immune deficiency was detected in 20% of patients and a significant percentage of the patients were found by reflex testing at globulin levels <16 g/L. During the study period the screening detected new light chain and non-secretory MM in 2.2% of patients. Three patients with CVID and six patients with light chain myeloma were previously detected by screening, consequently alerting clinicians and reducing delay in treatment. A further 23% with several co-morbid conditions showed unexpected hypogammaglobulinemia; in this category, the study identified a subgroup that required further investigation. Conclusion: Investigation of low globulin levels detects patients with primary and secondary immune deficiency and MM. Optimizing treatment for decreased immunoglobulins in patients with other clinical co-morbidities may require increased clinician awareness and watchful clinical and laboratory assessment.
Language	English
Publishing date	2023-05-30
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2587464-0
ISSN	1179-2736
ISSN	1179-2736
DOI	10.2147/JBM.S409234
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Article: Highly sensitive troponin I assay in the diagnosis of coronary artery disease in patients with suspected stable angina.

Ramasamy, Indra

World journal of cardiology

2021 Volume 13, Issue 12, Page(s) 745–757

Abstract: Background: Evaluation of suspected stable angina patients with probable coronary artery disease (CAD) in the community is challenging. In the United Kingdom, patients with suspected stable angina are referred by community physicians to be assessed by ... ...

Abstract	Background: Evaluation of suspected stable angina patients with probable coronary artery disease (CAD) in the community is challenging. In the United Kingdom, patients with suspected stable angina are referred by community physicians to be assessed by specialists within the hospital system in rapid access chest pain clinics (RACPC). The role of a highly sensitive troponin I (uscTnI) assay in the diagnosis of suspected CAD in a RACPC in a "real-life" setting in a non-academic hospital has not been explored. Aim: To examine the diagnostic value of uscTnI (detection limit 0.12 ng/L, upper reference range 8.15 ng/L, and detected uscTnI in 96.8% of the reference population), in the evaluation of stable CAD in a non-selected patient group, with several co-morbidities, who presented to the RACPC. Methods: One hundred and seventy two RACPC patients were assigned to either functional or anatomical testing according to the hospital protocol. Results: The investigations offered to patients were exercise tolerance test 7.6%, 24 h ECG 1.2%, Echocardiogram 14.5%, stress echocardiogram 8.1%, coronary computed tomography angiography (CCTA) 12.8%, coronary angiogram 13.4%, 17.4% were diagnosed with non-cardiac chest pain, 3.5% treated as stable angina, 8.2% reviewed by cardiologists, electronic medical records were not available in 10.4%. Receiver operating characteristic curves for CAD used uscTnI values measured in patients who underwent functional testing, angiogram or CCTA. Values > 0.52 ng/L showed 100% sensitivity and at > 11.6 ng/L showed 100% specificity. In the range > 0.52-11.6 ng/L, uscTnI may not have the same diagnostic potential. In patients assigned to coronary angiogram higher concentrations of uscTnI was associated with severe CAD. Low levels of uscTnI and low pre-test probability of CAD (QRISK3) may decrease patient numbers assigned to CCTA. Conclusion: The uscTnI diagnostic cut-off values in a RACPC will depend on patient population and their presenting co-morbidity. In the presence of clinical comorbidities and previous CAD the uscTnI needs to be used in conjunction with clinical assessment.
Language	English
Publishing date	2021-12-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2573665-6
ISSN	1949-8462
ISSN	1949-8462
DOI	10.4330/wjc.v13.i12.745
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Article ; Online: Atypical hereditary spherocytosis phenotype associated with pseudohypokalaemia and a new variant in the band 3 protein.

Ramasamy, Indra

BMJ case reports

2020 Volume 13, Issue 12

Abstract: Red blood cell (RBC) membrane disorders are predominantly caused by mutations resulting in decreased RBC deformability and permeability. We present a family in which, the proband and his daughter presented with pseudohypokalaemia. Studies on the ... ...

Abstract	Red blood cell (RBC) membrane disorders are predominantly caused by mutations resulting in decreased RBC deformability and permeability. We present a family in which, the proband and his daughter presented with pseudohypokalaemia. Studies on the temperature dependence of pseudohypokalaemia suggested a maximum decrease in serum potassium when whole blood is stored at 37°C. Routine haematology suggested mild haemolysis with a hereditary spherocytosis phenotype. These two cases present a novel variant in temperature-dependent changes in potassium transport. A new variant was identified in the SLC4A1 gene which codes for band 3 protein (anion exchanger 1) in RBC membrane which may contribute to the phenotype. This is the first report of familial pseudohypokalaemia associated with changes in RBC membrane morphology. The clinical implications of pseudohypokalaemia are that it can lead to inappropriate investigation or treatment. However, many questions remain to be solved and other RBC membrane protein genes should be studied.
MeSH term(s)	Anion Exchange Protein 1, Erythrocyte/genetics ; Erythrocytes/metabolism ; Erythrocytes/pathology ; Humans ; Hypokalemia/blood ; Male ; Middle Aged ; Mutation ; Phenotype ; Potassium/blood ; Spherocytosis, Hereditary/blood ; Spherocytosis, Hereditary/genetics ; Spherocytosis, Hereditary/pathology
Chemical Substances	Anion Exchange Protein 1, Erythrocyte ; SLC4A1 protein, human ; Potassium (RWP5GA015D)
Language	English
Publishing date	2020-12-09
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2020-238428
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Article: Vitamin D Metabolism and Guidelines for Vitamin D Supplementation.

Ramasamy, Indra

The Clinical biochemist. Reviews

2020 Volume 41, Issue 3, Page(s) 103–126

Abstract: Vitamin D is essential for bone health and is known to be involved in immunomodulation and cell proliferation. Vitamin D status remains a significant health issue worldwide. However, there has been no clear consensus on vitamin D deficiency and its ... ...

Abstract	Vitamin D is essential for bone health and is known to be involved in immunomodulation and cell proliferation. Vitamin D status remains a significant health issue worldwide. However, there has been no clear consensus on vitamin D deficiency and its measurement in serum, and clinical practice of vitamin D deficiency treatment remains inconsistent. The major circulating metabolite of vitamin D, 25-hydroxyvitamin D (25(OH)D), is widely used as a biomarker of vitamin D status. Other metabolic pathways are recognised as important to vitamin D function and measurement of other metabolites may become important in the future. The utility of free 25(OH)D rather than total 25(OH)D needs further assessment. Data used to estimate the vitamin D intake required to achieve a serum 25(OH)D concentration were drawn from individual studies which reported dose-response data. The studies differ in their choice of subjects, dose of vitamin D, frequency of dosing regimen and methods used for the measurement of 25(OH)D concentration. Baseline 25(OH)D, body mass index, ethnicity, type of vitamin D (D
Language	English
Publishing date	2020-11-18
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	1018054-0
ISSN	1838-0212 ; 0159-8090
ISSN (online)	1838-0212
ISSN	0159-8090
DOI	10.33176/AACB-20-00006
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Article: A Single-Center Retrospective Study to Investigate the Follow-Up of Patients with Monoclonal Proteinemia by Community Physicians in the UK.

Ramasamy, Indra

Journal of blood medicine

2020 Volume 11, Page(s) 191–203

Abstract: Background: We determined the detection rate of monoclonal gammopathy of undetermined significance (MGUS) and follow-up of MGUS patients in a center that uses reflex testing at globulin levels outside the reference range as part of its routine service ... ...

Abstract	Background: We determined the detection rate of monoclonal gammopathy of undetermined significance (MGUS) and follow-up of MGUS patients in a center that uses reflex testing at globulin levels outside the reference range as part of its routine service to detect monoclonal protein (M-protein). We recorded the natural history and follow-up of these patients. This is one of the first reports on the diagnosis and follow-up of MGUS patients within the UK. Patients and methods: A total of 163 patients diagnosed in 2006 and 393 patients with M-protein on long-term follow-up in 2006 were followed over a period of 10 years (y) by community physicians with laboratory support. Results: In 2006, newly diagnosed patients with an M-protein and total number of patients as a percentage of the Worcestershire population were, respectively, 0.025%, 0.045% (at 45-49y); 0.1%, 0.25% (at 60-64y); and 0.26%, 1.12% (at 75-79y). Patients with M-protein had a survival of 35.5% at 10 y and 43.5% at >10y follow-up. Kaplan-Meier analysis of patients with an M-protein showed that lymphoplasma-cell proliferative disorders (LPD)-free survival was 91% for both 10y and >10y follow-up. LPD-free survival decreased to approximately 73% when competing causes (death due to unrelated causes, transient M-protein, loss to follow-up) were censored. Progression to LPD occurred at initial M-protein values of 3g/L at diagnosis. During follow-up, 38.3% died without evidence of LPD, 12% were diagnosed with transient M-protein, 8.7% developed LPD, 10.9% had stable M-protein, 4.9% showed increasing M-protein, and 25.2% were lost to follow-up. Survival curves showed that M-protein isotype contributed to LPD-free survival in the order IgG=IgM>IgA>biclonal M-protein. Conclusion: Geographical variations in the diagnosis and follow-up of MGUS patients in the UK need investigation. From public health viewpoint, it is essential to determine MGUS follow-up to improve clinical care and individualise risk-based follow-up of patients.
Language	English
Publishing date	2020-06-11
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2587464-0
ISSN	1179-2736
ISSN	1179-2736
DOI	10.2147/JBM.S255390
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Article ; Online: Recent advances in physiological lipoprotein metabolism.

Ramasamy, Indra

Clinical chemistry and laboratory medicine

2014 Volume 52, Issue 12, Page(s) 1695–1727

Abstract: Research into lipoprotein metabolism has developed because understanding lipoprotein metabolism has important clinical indications. Lipoproteins are risk factors for cardiovascular disease. Recent advances include the identification of factors in the ... ...

Abstract	Research into lipoprotein metabolism has developed because understanding lipoprotein metabolism has important clinical indications. Lipoproteins are risk factors for cardiovascular disease. Recent advances include the identification of factors in the synthesis and secretion of triglyceride rich lipoproteins, chylomicrons (CM) and very low density lipoproteins (VLDL). These included the identification of microsomal transfer protein, the cotranslational targeting of apoproteinB (apoB) for degradation regulated by the availability of lipids, and the characterization of transport vesicles transporting primordial apoB containing particles to the Golgi. The lipase maturation factor 1, glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 and an angiopoietin-like protein play a role in lipoprotein lipase (LPL)-mediated hydrolysis of secreted CMs and VLDL so that the right amount of fatty acid is delivered to the right tissue at the right time. Expression of the low density lipoprotein (LDL) receptor is regulated at both transcriptional and post-transcriptional level. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a pivotal role in the degradation of LDL receptor. Plasma remnant lipoproteins bind to specific receptors in the liver, the LDL receptor, VLDL receptor and LDL receptor-like proteins prior to removal from the plasma. Reverse cholesterol transport occurs when lipid free apoAI recruits cholesterol and phospholipid to assemble high density lipoprotein (HDL) particles. The discovery of ABC transporters (ABCA1 and ABCG1) and scavenger receptor class B type I (SR-BI) provided further information on the biogenesis of HDL. In humans HDL-cholesterol can be returned to the liver either by direct uptake by SR-BI or through cholesteryl ester transfer protein exchange of cholesteryl ester for triglycerides in apoB lipoproteins, followed by hepatic uptake of apoB containing particles. Cholesterol content in cells is regulated by several transcription factors, including the liver X receptor and sterol regulatory element binding protein. This review summarizes recent advances in knowledge of the molecular mechanisms regulating lipoprotein metabolism.
MeSH term(s)	ATP-Binding Cassette Transporters/metabolism ; Apolipoproteins/biosynthesis ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/pathology ; Cholesterol Ester Transfer Proteins/metabolism ; Chylomicrons/metabolism ; Humans ; Lipoproteins/metabolism ; Lipoproteins, HDL/biosynthesis ; Lipoproteins, VLDL/biosynthesis ; Phospholipid Transfer Proteins/metabolism ; Receptors, Scavenger/metabolism
Chemical Substances	Apolipoproteins ; Cholesterol Ester Transfer Proteins ; Chylomicrons ; Lipoproteins ; Lipoproteins, HDL ; Lipoproteins, VLDL ; Phospholipid Transfer Proteins ; Receptors, Scavenger
Language	English
Publishing date	2014-12
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2013-0358
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Article ; Online: Ligand-Dependent Downregulation of Guanylyl Cyclase/Natriuretic Peptide Receptor-A: Role of miR-128 and miR-195.

Khurana, Madan L / Mani, Indra / Kumar, Prerna / Ramasamy, Chandramohan / Pandey, Kailash N

International journal of molecular sciences

2022 Volume 23, Issue 21

Abstract: Cardiac hormones act on the regulation of blood pressure (BP) and cardiovascular homeostasis. These hormones include atrial and brain natriuretic peptides (ANP, BNP) and activate natriuretic peptide receptor-A (NPRA), which enhance natriuresis, diuresis, ...

Abstract	Cardiac hormones act on the regulation of blood pressure (BP) and cardiovascular homeostasis. These hormones include atrial and brain natriuretic peptides (ANP, BNP) and activate natriuretic peptide receptor-A (NPRA), which enhance natriuresis, diuresis, and vasorelaxation. In this study, we established the ANP-dependent homologous downregulation of NPRA using human embryonic kidney-293 (HEK-293) cells expressing recombinant receptor and MA-10 cells harboring native endogenous NPRA. The prolonged pretreatment of cells with ANP caused a time- and dose-dependent decrease in
MeSH term(s)	Humans ; Guanylate Cyclase/genetics ; Guanylate Cyclase/metabolism ; Atrial Natriuretic Factor/genetics ; Atrial Natriuretic Factor/pharmacology ; Atrial Natriuretic Factor/metabolism ; Ligands ; Down-Regulation ; HEK293 Cells ; Cyclic GMP/metabolism ; MicroRNAs/genetics ; Natriuretic Peptide, Brain/metabolism
Chemical Substances	Guanylate Cyclase (EC 4.6.1.2) ; Atrial Natriuretic Factor (85637-73-6) ; Iodine-125 (GVO776611R) ; Ligands ; Cyclic GMP (H2D2X058MU) ; MicroRNAs ; Natriuretic Peptide, Brain (114471-18-0) ; MIRN128 microRNA, human ; MIRN195 microRNA, human
Language	English
Publishing date	2022-11-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232113381
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Article ; Online: Ligand-Dependent Downregulation of Guanylyl Cyclase/Natriuretic Peptide Receptor-A

Madan L. Khurana / Indra Mani / Prerna Kumar / Chandramohan Ramasamy / Kailash N. Pandey

International Journal of Molecular Sciences, Vol 23, Iss 13381, p

Role of miR-128 and miR-195

2022 Volume 13381

Abstract	Cardiac hormones act on the regulation of blood pressure (BP) and cardiovascular homeostasis. These hormones include atrial and brain natriuretic peptides (ANP, BNP) and activate natriuretic peptide receptor-A (NPRA), which enhance natriuresis, diuresis, and vasorelaxation. In this study, we established the ANP-dependent homologous downregulation of NPRA using human embryonic kidney-293 (HEK-293) cells expressing recombinant receptor and MA-10 cells harboring native endogenous NPRA. The prolonged pretreatment of cells with ANP caused a time- and dose-dependent decrease in 125 I-ANP binding, Guanylyl cyclase (GC) activity of receptor, and intracellular accumulation of cGMP leading to downregulation of NPRA. Treatment with ANP (100 nM) for 12 h led to an 80% decrease in 125 I-ANP binding to its receptor, and BNP decreased it by 62%. Neither 100 nM c-ANF (truncated ANF) nor C-type natriuretic peptide (CNP) had any effect. ANP (100 nM) treatment also decreased GC activity by 68% and intracellular accumulation cGMP levels by 45%, while the NPRA antagonist A71915 (1 µM) almost completely blocked ANP-dependent downregulation of NPRA. Treatment with the protein kinase G (PKG) stimulator 8-(4-chlorophenylthio)-cGMP (CPT-cGMP) (1 µM) caused a significant increase in 125 I-ANP binding, whereas the PKG inhibitor KT 5823 (1 µM) potentiated the effect of ANP on the downregulation of NPRA. The transfection of miR-128 significantly reduced NPRA protein levels by threefold compared to control cells. These results suggest that ligand-dependent mechanisms play important roles in the downregulation of NPRA in target cells.
Keywords	GC/NPRA ; HEK-293 cells ; MA-10 cells ; internalization ; ANP-NPRA/cGMP signaling ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Epigenetically modified nucleobases (5hmc, 5fc, and 5caC) interaction with boron and nitrogen doped porous graphene (B/N-pGr) as promising materials for biosensing application: A density functional theory calculations.

Saravanan, Vinnarasi / Rajamani, Akilan / Ramasamy, Shankar / Baazeem, Alaa / Upadhyaya, Indra Raj

Environmental research

2021 Volume 197, Page(s) 111133

Abstract: In this present work, porous graphene (pGr), boron (B-pGr), and nitrogen (N-pGr) doped porous sheets are explored as a bio-sensor device for sensing modified nucleobases (MBs) in cancer therapy using density functional theory (DFT). The obtained ... ...

Abstract	In this present work, porous graphene (pGr), boron (B-pGr), and nitrogen (N-pGr) doped porous sheets are explored as a bio-sensor device for sensing modified nucleobases (MBs) in cancer therapy using density functional theory (DFT). The obtained geometrical, energetic and electronic properties revealed that the B-pGr is highly reactive and it adsorbs MBs better than the pGr and N-pGr, because B atom holds empty p-orbitals which easily interact with partially filled p-orbital of N and O atom. Thus, the adsorption energies of 5hmc, 5caC, and 5fc on B-pGr are high rather than the pGr and N-pGr. The corresponding adsorption energies are -96.074, -77.0, and -60.721 kcal/mol for 5hmc, 5caC, and 5fc respectively. The positive signature of ΔN values (0.005 eV, 0.076 eV, and 0.047 in MBs on pGr and 0.171 eV, 0.252 eV and 0.205 eV in MBs on N-pGr) are obtained at MBs on pGr and N-pGr complex. The negative ΔN values (-0.141 eV, -0.032 eV, and -0.061 eV in MBs on B-pGr) are obtained at MBs of B-pGr. The calculated absorption values shows that the B-pGr is strongly adsorbed MBs at 342 nm. The obtained results exhibit that the B-pGr sheet retains significant therapeutic potential as a bio-sensing application for cancer therapy.
MeSH term(s)	Boron ; Density Functional Theory ; Graphite ; Nitrogen ; Porosity
Chemical Substances	Graphite (7782-42-5) ; Nitrogen (N762921K75) ; Boron (N9E3X5056Q)
Language	English
Publishing date	2021-04-18
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2021.111133
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