Publications by authors named "Soham Mukherjee"

29 Publications

  • Page 1 of 1

Determining clinically relevant features in cytometry data using persistent homology.

bioRxiv 2021 Apr 27. Epub 2021 Apr 27.

Cytometry experiments yield high-dimensional point cloud data that is difficult to interpret manually. Boolean gating techniques coupled with comparisons of relative abundances of cellular subsets is the current standard for cytometry data analysis. However, this approach is unable to capture more subtle topological features hidden in data, especially if those features are further masked by data transforms or significant batch effects or donor-to-donor variations in clinical data. We present that persistent homology, a mathematical structure that summarizes the topological features, can distinguish different sources of data, such as from groups of healthy donors or patients, effectively. Analysis of publicly available cytometry data describing non-naïve CD8+ T cells in COVID-19 patients and healthy controls shows that systematic structural differences exist between single cell protein expressions in COVID-19 patients and healthy controls. Our method identifies proteins of interest by a decision-tree based classifier and passes them to a kernel-density estimator (KDE) for sampling points from the density distribution. We then compute persistence diagrams from these sampled points. The resulting persistence diagrams identify regions in cytometry datasets of varying density and identify protruded structures such as 'elbows'. We compute Wasserstein distances between these persistence diagrams for random pairs of healthy controls and COVID-19 patients and find that systematic structural differences exist between COVID-19 patients and healthy controls in the expression data for T-bet, Eomes, and Ki-67. Further analysis shows that expression of T-bet and Eomes are significantly downregulated in COVID-19 patient non-naïve CD8+ T cells compared to healthy controls. This counter-intuitive finding may indicate that canonical effector CD8+ T cells are less prevalent in COVID-19 patients than healthy controls. This method is applicable to any cytometry dataset for discovering novel insights through which may be difficult to ascertain otherwise with a standard gating strategy or in the presence of large batch effects.

Author Summary: Identifying differences between cytometry data seen as a point cloud can be complicated by random variations in data collection and data sources. We apply used in to describe the shape and structure of the data representing immune cells in healthy donors and COVID-19 patients. By looking at how the shape and structure differ between healthy donors and COVID-19 patients, we are able to definitively conclude how these groups differ despite random variations in the data. Furthermore, these results are novel in their ability to capture shape and structure of cytometry data, something not described by other analyses.
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http://dx.doi.org/10.1101/2021.04.26.441473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095200PMC
April 2021

Dipeptidyl peptidase-4 inhibitor use and mortality in COVID-19 patients with diabetes mellitus: an updated systematic review and meta-analysis.

Ther Adv Endocrinol Metab 2021 20;12:2042018821996482. Epub 2021 Feb 20.

Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.

Background: Few observational studies have shown a beneficial effect of dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with coronavirus disease 2019 (COVID-19), although results are not consistent. The present systematic review and meta-analysis was undertaken to provide a precise summary of the effect of DPP4i use (preadmission or in-hospital) and mortality in COVID-19 patients with diabetes mellitus (DM).

Methods: PubMed and Google Scholar databases were systematically searched using appropriate keywords to 4 January 2021, to identify observational studies reporting mortality in COVID-19 patients with DM using DPP4i those not using DPP4i. Preadmission and in-hospital use of DPP4i were considered. Study quality was assessed using the Newcastle-Ottawa Scale. Unadjusted and adjusted pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Subgroup analysis was performed for studies reporting preadmission and in-hospital use of DPP4i.

Results: We identified nine observational studies of high quality pooling data retrieved from 7008 COVID-19 patients with DM. The pooled analysis of unadjusted and adjusted data did not show any significant association between DPP4i use and mortality in COVID-19 patients with DM. However, on subgroup analysis, we found that in-hospital (and not preadmission) DPP4i use was associated with reduced mortality (unadjusted OR 0.37, 95% CI 0.23, 0.58,  < 0.0001,  = 0% and adjusted OR 0.27, 95% CI 0.13, 0.55,  = 0.0003,  = 12%).

Conclusions: In-hospital use of DPP4i is associated with a significant reduction in COVID-19 mortality. Hence, it would be prudent to initiate or continue DPP4i in COVID-19 patients with DM if not contraindicated.
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http://dx.doi.org/10.1177/2042018821996482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897812PMC
February 2021

Parathyroid Carcinoma: An Experience from the Indian Primary Hyperparathyroidism Registry.

Endocr Pract 2021 Jan 27. Epub 2021 Jan 27.

Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: To describe the details of widely invasive parathyroid carcinoma (WIPC) patients admitted in the Endocrinology department of our institute during the last 22 years and to compare their clinical, biochemical, and hormonal profile with minimally invasive parathyroid carcinoma (MIPC) and sporadic parathyroid adenoma patients.

Methods: This is a retrospective analysis of data from the Indian primary hyperparathyroidism registry.

Results: Of the 547 primary hyperparathyroidism patients in the registry, 5 (2 men and 3 women) had WIPC (0.9%) and 7 (1 man and 6 women) had MIPC (1.3%), with median ages of 45 (interquartile range, 41-51) years and 47 (interquartile range, 28-48) years, respectively. Among the patients with WIPC, renal manifestations were present in 5 patients, skeletal manifestations in 4 patients, and palpable neck masses in 4 patients. Three patients had distant metastases and 2 had cervical lymph node involvement. All 5 patients had surgical resection of their cancers, with persistent disease in 4 patients, but all patients died within 2 years after surgery. One patient with MIPC had a palpable parathyroid nodule; none had lymph nodal or distant metastases. None of the patients with MIPC died during the median follow-up of 18 (interquartile range, 12-18) months. Patients with WIPC had significantly higher serum calcium level compared with sporadic parathyroid adenoma patients with skeletal and renal manifestations.

Conclusion: Accurate histopathologic classification of parathyroid carcinoma is important as WIPC is associated with a more aggressive clinical course and a higher risk of mortality than MIPC.
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http://dx.doi.org/10.1016/j.eprac.2021.01.014DOI Listing
January 2021

Impaired anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with diabetes mellitus: A preliminary report.

Diabetes Metab Syndr 2021 Jan-Feb;15(1):193-196. Epub 2020 Dec 25.

Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. Electronic address:

Background And Aims: Patients with diabetes mellitus (DM) often demonstrate impaired antibody response to influenza/hepatitis B vaccines. Hence, we compared anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with and without type 2 diabetes mellitus (T2DM).

Methods: Records of non-severe COVID-19 patients admitted at our institution between April 10, 2020 and May 20, 2020 were retrieved. Qualitative detection of total (IgG + IgM) anti-SARS-CoV-2 antibody was performed using electrochemiluminescence immunoassay in plasma samples collected at least 14 days post-polymerase chain reaction (PCR) confirmation of diagnosis.

Results: Thirty-one non-severe COVID-19 patients were included. Nine patients (29%) had T2DM with mean HbA at admission of 8.3 ± 1.0%. Anti-SARS-CoV-2 antibody was estimated at a median of 16 (14-17) days post-PCR confirmation of COVID-19 diagnosis. Only three patients (10%) were seronegative, and all had T2DM. Patients with T2DM were more likely to have non-detectable anti-SARS-CoV-2 antibodies than those without DM (p = 0.019).

Conclusions: COVID-19 patients with T2DM may not undergo seroconversion even after two weeks of diagnosis. Impaired seroconversion could theoretically increase the risk of reinfections in patients with DM. However, the finding requires validation in large-scale studies involving serial estimations of anti-SARS-CoV-2 antibodies in patients with and without DM.
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http://dx.doi.org/10.1016/j.dsx.2020.12.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762626PMC
March 2021

Stabilization of a potential anticancer thiosemicarbazone derivative in Sudlow site I of human serum albumin: In vitro spectroscopy coupled with molecular dynamics simulation.

Biophys Chem 2021 Feb 30;269:106509. Epub 2020 Nov 30.

Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra 440010, India. Electronic address:

Human Serum Albumin (HSA) is the most important protein in human blood plasma and can acts as a major transporting agent for various drug molecules with flexible binding interaction. To elucidate the interaction of a newly designed potential anticancer thiosemicarbazone based luminophore (E)-1-(4-(diethylamino)-2-hydroxybenzylidene)-4,4-dimethyl-thiosemicarbazide (DAHTS) with HSA under physiological condition, in vitro optical spectroscopic experiments viz UV-Vis absorption, steady state fluorescence, fluroscence anisotropy, time resolved fluorscence (TRF) and cicular dichroism (CD) spectroscopy have been scrutinised. The experimental findings have been corroborated with in silico molecular docking analysis and Molecular Dynamics (MD) simulation. The spectroscopic results demonstrated that the conventionally anion-favouring Sudlow site I of HSA copiously adapt neutral DAHTS molecule with moderate binding affinity. The mean fluorescence lifetime of the sole tryptophan (Trp-214) present in the macromolecule experiences an appreciable diminution with an increase in concentration of the synthesized molecule. DAHTS localize itself close to Trp-214 within subdomain IIA (Sudlow site I) and surrounded by multiple hydrophobic amino acid residues (Val-235, Val-231, Ala-229, Phe-228, Val-325, Phe-326, Leu-327, Met-329, Phe-330, Leu-331, Tyr-332, Leu-346, Leu-347, Val-482, Leu-349, Ala-350, Ala-210, Trp-214, Ala- 213 and Val-216) in HSA. The distinct fluorescence lifetime, diverse pathways and changing rate of population indicates that the rotamerisation of Trp-214 residue is controlled by the guest molecule. Sudlow site I of HSA behaves flexibly and induces an allosteric modulation in the macromolecule resulting a minor deformation in the protein secondary structure as observed in CD (observed 11% change of α-helix content) as well as in MD simulation. The integrated multi-spectroscopic research described herein provides several important information about the binding interaction of a thiosemicarbazone Schiff base with HSA, which can be very significant for thiosemicarbazone based drug designing for academia as well as industry.
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http://dx.doi.org/10.1016/j.bpc.2020.106509DOI Listing
February 2021

A Novel Near Infrared Spectroscopy Based Device for Albumin Estimation.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:6123-6126

In this paper we have proposed a fluorescence based spectroscopy device which can be used to quantitatively estimate the amount of albumin that gets excreted out of our body. Albumin is a significant protein in bio-fluids and performs a wide range of metabolic functions. The dye that has been used as a fluorescent indicator for the presence of albumin in this study has been earlier tested with bovine serum albumin (BSA) and human serum albumin (HSA) with satisfactory results. The method is based on principle of fluorescence in near infrared range (NIR) of 700 to 850 nm by using a novel dye with the test mixture. The chosen near infrared range has a benefit of absence of the auto fluorescence of the bio-molecules present in urine other than the albumin molecules. The system consists of: light source, spectroscopic chamber, sensing and computational unit. The study shows the stability and reproducibility of device so as to avoid fluctuations of voltage and other undesirables. The optimization with bovine serum albumin and human serum albumin has been done and the device can sense as low as 100 nM concentration precisely and accurately.Clinical Relevance-The system being presented is intended for developing a low cost point of care testing device for determining albumin concentration in urine.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176046DOI Listing
July 2020

Progressive rise in the prevalence of asymptomatic primary hyperparathyroidism in India: Data from PHPT registry.

J Bone Miner Metab 2021 Mar 7;39(2):253-259. Epub 2020 Sep 7.

Bone and Mineral Research Laboratory, Henry Ford Hospital, Detroit, USA.

Introduction: Primary hyperparathyroidism (PHPT), a third common endocrine disorder, varies from asymptomatic disease, mostly seen in the West where routine biochemical screening is practiced, to the classical symptomatic disease mostly seen in the Eastern countries. We aimed to compare the demographic, clinical, biochemical measurements in patients with asymptomatic and symptomatic PHPT from the Indian PHPT registry.

Material And Methods: Data of PHPT patients from the last 25 years (1995-2019) were analyzed for demographic, clinical presentation and biochemical measurements, and compared these characteristics between asymptomatic and symptomatic PHPT patients.

Results: Of the 554 patients, 54 (10%) patients had asymptomatic PHPT. There was a sharp rise in the proportion of asymptomatic PHPT patients of 3% in the first decade to 13% in the second decade of the century (p = 0.003). Patients with asymptomatic PHPT were significantly older (50 vs. 42 years; p < 0.0001) and had higher mean body mass index (27.8 vs. 23.5 kg/m; p < 0.0001) compared to the symptomatic PHPT group. In addition, asymptomatic PHPT patients had significantly lower median plasma iPTH (180 vs. 370 pg/mL; p < 0.0001), serum alkaline phosphatase (119 vs. 172 IU/L; p < 0.0001), and parathyroid adenoma weight (1.0 vs. 2.62 g; p = 0.006) compared to the symptomatic PHPT group.

Conclusion: Although symptomatic PHPT is still most prevalent (> 90%) in India with higher indices of the disease and tumor weights, there is a progressive rise in the prevalence of asymptomatic PHPT patients in the last decade. Improvements in calcium and vitamin D nutrition might account for this change as in the Western series.
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http://dx.doi.org/10.1007/s00774-020-01142-wDOI Listing
March 2021

Persistence of "non-dipping" pattern in blood pressure after curative parathyroidectomy in apparently normotensive patients with symptomatic primary hyperparathyroidism.

Minerva Endocrinol 2020 Sep 28;45(3):181-188. Epub 2019 Nov 28.

Departments of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: The prevalence of hypertension in primary hyperparathyroidism (PHPT) varies from 20-80% with data being based on office-based blood pressure measurements. Little is known about ambulatory monitoring of blood pressure (AMBP) in PHPT and changes in blood pressure (BP) variables post-curative parathyroidectomy. Hence, we conducted a prospective study wherein we performed AMBP in apparently normotensive patients with PHPT and reevaluated them 3 months post-curative parathyroidectomy.

Methods: Consecutive patients with symptomatic PHPT aged 20 years and above underwent 24 hours AMBP at enrollment and at 3 months after successful parathyroidectomy. Pre- and postoperative BP variables were compared and correlated with serum calcium, creatinine and intact parathyroid hormone (iPTH) levels.

Results: After exclusion, 17 symptomatic PHPT patients were enrolled in the study. AMBP detected hypertension in 4 (23.5%) patients. There was a significant reduction in the average nighttime systolic (P=0.007) and diastolic BP (P=0.034) after parathyroidectomy. However, the average 24 hours systolic/diastolic BP, daytime systolic/diastolic BP and average 24 hours mean arterial pressure did not differ before and after surgery. Non-dipping blood pressure pattern was seen in 53% of patients at presentation and persisted in 50% of cases after successful surgery. None of the biochemical parameters significantly correlated with any BP variable.

Conclusions: AMBP can help detect hypertension in patients with PHPT that remains unrecognized with routine office-based blood pressure measurement. In addition, AMBP detects loss of normal dipping pattern in BP that persists in almost half of the patients even after successful parathyroidectomy, perhaps because of permanent vascular damage induced by PHPT.
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http://dx.doi.org/10.23736/S0391-1977.19.03104-3DOI Listing
September 2020

Entrapment in micellar assemblies switches the excimer population of potential therapeutic luminophore azapodophyllotoxin.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Mar 9;228:117723. Epub 2019 Nov 9.

Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra, 440010, India. Electronic address:

Azapodophyllotoxin is a new class of anti-tumor agent with brilliant therapeutic activity and understanding its physicochemical nature in bio-mimetic microenvironments may provide substantial importance in context of its intercellular localization, efficacy as well as delivery. The present work epitomizes environment-sensitive fluorescence modulation of a prodigy, 4-(2-Hydroxyethyl)-10-phenyl-3,4,6,7,8,10- hexahydro-1H-cyclopenta[g]furo[3,4-b]quinoline-1-one (HPFQ) from the class of anti-cancer agent Azapodophyllotoxin, in differently charged model bio-mimetic micellar microenvironment of cationic CTAB, anionic SDS and neutral Triton X-100 using UV-visible absorption, steady state fluorescence, time-resolved fluorescence and fluorescence anisotropy studies. As a distinct phenomenon, anticancer HPFQ exhibits prolific fluorescence in solvents of varying polarity, originating from a mixed contribution of locally excited, charge transfer and excimer emission. A dramatic modulation in the photophysics of HPFQ has been observed in two types of surfactant consortiums: pre-micellar and post-micellar at physiological and anoxic pH. On photo-excitation, anti-cancer HPFQ exists in monomer-excimer equilibrium with varying ratios in different polarity regions. The marked enhancement in fluorescence intensity of HPFQ in post-micellar region of the surfactant under study probably arises due to regeneration of the monomer from its excimer. This reoccurrence reduces the possibility of Förster resonance energy transfer (FRET) from monomer to excimer, which essentially increases the desired emission intensity. Localization of HPFQ in micellar systems highly depends on polarity gradient inside the micelle, electrostatic, hydrophobic and intermolecular hydrogen bonding interactions. Further corroboration with the polarity sensitive experiments in dioxane-water mixture indicates towards spatial localization of the probe molecule in the stern layer of cationic CTAB, sheer surface of neutral TX100 and outer Gouy-Chapman layer in anionic SDS micelles. A molecular binary logic gate correlates the dominance of micellization over the polarity factor, which enhances the fluorescence response of HPFQ. The enhancement of the emissive potential of anti-cancer HPFQ in biomimetic environments by switching its excimer population may have an immense importance to achieve the status of a dual therapeutic and imaging agent altogether in progressive biomedical research.
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http://dx.doi.org/10.1016/j.saa.2019.117723DOI Listing
March 2020

Association of Pseudohypoparathyroidism and Autoimmune Polyglandular Syndrome: Causal or Coincidental?

Indian J Clin Biochem 2019 Oct 10;34(4):490-492. Epub 2018 Dec 10.

2Department of Endocrinology, PGIMER, Chandigarh, India.

Pseudohypoparathyroidism (PHP) is a state of parathyroid hormone resistance and is characterised by low serum calcium, and elevated serum phosphate and parathyroid hormone level. Association of PHP with autoimmune disorders is rare and seldom reported in the literature. Here we describe a case of PHP who subsequently developed multiple autoimmune disorders (type 3 polyglandular autoimmune syndrome), which has not been reported so far.
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http://dx.doi.org/10.1007/s12291-018-0802-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801268PMC
October 2019

Cesium Bismuth Iodide Solar Cells from Systematic Molar Ratio Variation of CsI and BiI.

Inorg Chem 2019 Sep 4;58(18):12040-12052. Epub 2019 Sep 4.

Ångström Laboratory, Division of Physical Chemistry, Department of Chemistry , Uppsala University , Box 523 , SE-75120 Uppsala , Sweden.

Metal halide compounds with photovoltaic properties prepared from solution have received increased attention for utilization in solar cells. In this work, low-toxicity cesium bismuth iodides are synthesized from solution, and their photovoltaic and optical properties as well as electronic and crystal structures are investigated. The X-ray diffraction patterns reveal that a CsI/BiI precursor ratio of 1.5:1 can convert pure rhombohedral BiI to pure hexagonal CsBiI, but any ratio intermediate of this stoichiometry and pure BiI yields a mixture containing the two crystalline phases CsBiI and BiI, with their relative fraction depending on the CsI/BiI ratio. Solar cells from the series of compounds are characterized, showing the highest efficiency for the compounds with a mixture of the two structures. The energies of the valence band edge were estimated using hard and soft X-ray photoelectron spectroscopy for more bulk and surface electronic properties, respectively. On the basis of these measurements, together with UV-vis-near-IR spectrophotometry, measuring the band gap, and Kelvin probe measurements for estimating the work function, an approximate energy diagram has been compiled clarifying the relationship between the positions of the valence and conduction band edges and the Fermi level.
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http://dx.doi.org/10.1021/acs.inorgchem.9b01233DOI Listing
September 2019

Minimally invasive parathyroid carcinoma-A missing entity between parathyroid adenoma and carcinoma: Scintigraphic and histological features.

Clin Endocrinol (Oxf) 2019 12 3;91(6):842-850. Epub 2019 Oct 3.

Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Purpose: Minimally invasive parathyroid carcinoma (MIPC) is clinically and biochemically comparable with parathyroid adenoma (PA) though histopathologically differ from PA. MIPC is an intermediate of PA and parathyroid carcinoma (PC). In literature, there is no definite criterion to diagnose MIPC. Our aim was to evaluate and characterize the imaging and biochemical parameters with histological characteristics of MIPC.

Methodology: Ten patients with MIPC were recruited from (single centre) Indian PHPT registry (www.indianphptregistry.com) from January 2014 to July 2018. Clinical, biochemical, imaging and histological features of MIPC patients were reviewed.

Results: The mean age of MIPC patients (n = 10; 3 males) was 39.9 ± 11.3 years (range: 17-50). All patients had an elevated preoperative parathyroid hormone (iPTH) level ranging from 427 to 2138 pg/mL (median: 1328). MIBI scan showed intensely avid and enlarged parathyroid tumours in all patients; LIPT in 6, RIPT in 3 and ectopic mediastinal in 1 with mean size of the tumours was 2.8 ± 1.1 cm. The mean of maximum standardized uptake value (SUVmax) of MIPC in F-18 fluorocholine PET/CT was 6.7 ± 1.1 (range 6.0-8.3). The mean tumour weight was 12 ± 9.5 g (range: 1.09-28). All MIPC patients had identified capsular invasion in 80% and vascular invasion in 50% only but there was no local invasion, lymph nodal or distant metastasis. The mean Ki-67 labelling index was 3.2 ± 2.7 (range 1.1-10).

Conclusion: The study concluded that MIPC patients are less aggressive (on the basis of imaging and histopathological findings) and should be differentiated from parathyroid adenoma and carcinoma.
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http://dx.doi.org/10.1111/cen.14088DOI Listing
December 2019

Neuron-Astrocyte Liaison to Maintain Lipid Metabolism of Brain.

Trends Endocrinol Metab 2019 09 8;30(9):573-575. Epub 2019 Aug 8.

Centre for Brain Research (CBR), Indian Institute of Science (IISc), Bangalore-560012, India. Electronic address:

Neuron-astrocyte crosstalk is a tightly regulated process that is essential for overall proper functioning of the brain. Maria S. Ioannou et al. (Cell, 2019) revealed a novel and compelling function of neuron-astrocyte crosstalk that explains how neurons cope with their accumulating toxic lipid particles under various scenarios.
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http://dx.doi.org/10.1016/j.tem.2019.07.018DOI Listing
September 2019

The consequences of adopting therapeutic luminophore azapodophyllotoxin into BSA: a molecular regulator to control emissive population of two tryptophan residues in carrier protein.

J Biomol Struct Dyn 2020 May 22;38(8):2338-2351. Epub 2019 Jun 22.

Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra, India.

Bovine serum albumin (BSA) is a widely recognized plasma protein for its ubiquitous function as one of the paramount transporter of different drugs and enzymes inside biological systems. HPFQ, a member of azapodophyllotoxin family, has been observed to be highly bioactive against a majority of cancer cell lines; while subsequently showing impressive fluorescent properties throughout the polarity scale. However, further pursuit into compliance of this bioactive fluorophore with carrier protein remains imperative for excavating its suitable transporter inside human body. The present biophysical spectroscopic study attempts to exhibit the adaptability of BSA towards a potential therapeutic fluorophore (HPFQ) by combining optical spectroscopy and molecular docking. The competitive site-binding studies demonstrated that BSA nurtures neutral anti-cancer fluorophore HPFQ into Sudlow site I, where it experiences varying interactions with surrounding hydrophobic amino acid residues Phe 205, Trp 213, Ala 209, Leu 330, Ala 349, Leu 480 etc. HPFQ gets accommodated at the vicinity of Trp-213 in BSA and initiates operation of FRET between them. Adaptation of HPFQ encourages an allosteric modulation, leading to a minor deformation in secondary protein structure, which probably allows the invading water molecules to increase the micropolarity of the adjacent environment around Trp-213. HPFQ assumes to administer conformational alteration in BSA and regulate emissive population of two tryptophan residues Trp-134 and Trp-213. The amalgamated spectroscopic investigation described herein may encourage design of azapodophyllotoxin based potential therapeutic agents for effective bio-circulation using BSA-based drug distribution systems.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2019.1630320DOI Listing
May 2020

Frequency & predictors of pancreatitis in symptomatic primary hyperparathyroidism.

Indian J Med Res 2018 Dec;148(6):721-727

Department of Endocrinology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Background & Objectives: The frequency and predictors of pancreatitis in primary hyperparathyroidism (PHPT) are not well understood. The objective of the present study was to evaluate the frequency of pancreatitis in patients with PHPT and its association with clinical and biochemical parameters of the disease.

Methods: In this retrospective study all consecutive patients with PHPT registered in the PHPT registry (www.indianphptregistry.com) from the year 2004 to 2013 were included. The clinical, biochemical and radiological parameters related to pancreatitis were evaluated in histologically proven PHPT patients.

Results: A total of 218 patients (63 men; mean age: 40.6±14.4 yr) underwent surgery for PHPT during the study. Pancreatitis occurred in 35 [16%, 18 acute and 17 chronic pancreatitis (CP)] patients and male:female ratio was 1:0.94. Skeletal manifestations were seen less frequently in PHPT with pancreatitis as compared to that of PHPT without pancreatitis. PHPT with pancreatitis had significantly higher serum calcium (12.4±2.0 vs. 11.7±1.5 mg/dl, P <0.05) in comparison to PHPT without pancreatitis. PHPT with acute pancreatitis (AP) had higher serum calcium (P <0.05) and parathyroid hormone (PTH) (P <0.05) levels than PHPT with CP. Curative parathyroidectomy improved the symptoms associated with pancreatitis as there was no recurrence in AP group, whereas recurrence was observed only in about 10 per cent patients of the CP group.

Interpretation & Conclusions: Pancreatitis was observed in 16 per cent of PHPT patients with male predominance in the study population. No recurrence of AP was observed after curative surgery. It may be proposed that serum amylase with calcium and PTH should be measured in all patients of PHPT with pain abdomen to rule out pancreatitis.
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http://dx.doi.org/10.4103/ijmr.IJMR_353_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396558PMC
December 2018

Revealing the role of microstructure architecture on strength and ductility of Ni microwires by in-situ synchrotron X-ray diffraction.

Sci Rep 2019 Jan 11;9(1):79. Epub 2019 Jan 11.

Institut Pprime, CNRS - ENSMA - Université de Poitiers, Département Physique et Mécanique des Matériaux, 86961, Futuroscope, France.

Deformation mechanisms of cold drawn and electropolished nickel microwires are studied by performing in-situ monotonous and cyclic tensile tests under synchrotron radiation. X-ray diffraction tests allow probing elastic strains in the different grain families and establishing a link with the deformation mechanisms taking place within the microwires. The measurements were carried out on several microwires with diameters ranging from as-drawn 100 µm down to 40 µm thinned down by electropolishing. The as-drawn wires exhibit a core-shell microstructure with <111> fiber texture dominant in core and heterogeneous dual fiber texture <111> and <100> in the shell. Reduction of specimen size by electropolishing results in a higher yield stress and tensile strength along with reduced ductility. In-situ XRD analysis revealed that these differences are linked to the global variation in microstructure induced by shell removal with electropolishing, which in turn affects the load sharing abilities of grain families. This study thus proposes a new way to increase ductility and retain strength in nickel microwires across different diameters by tuning the microstructure architecture.
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http://dx.doi.org/10.1038/s41598-018-36472-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329826PMC
January 2019

A rare complication of bedside tracheotomy: Thyroid crisis.

Lung India 2019 Jan-Feb;36(1):77-79

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.4103/lungindia.lungindia_238_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330806PMC
January 2019

Switching of Trp-214 intrinsic rotamer population in human serum albumin: An insight into the aftermath of embracing therapeutic bioorganic luminophore azapodophyllotoxin into sudlow site I.

Bioorg Chem 2019 03 16;84:63-75. Epub 2018 Nov 16.

Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra 440010, India. Electronic address:

Human serum albumin is perceived to be the most abundant protein in human blood plasma and functions as a major carrier of different enzymes and drugs inside human body. The present article puts in an effort to demonstrate the attitude adopted by human serum albumin towards a potential therapeutic luminophore 4-(2-Hydroxyethyl)-10-phenyl-3,4,6,7,8,10-hexahydro-1H-cyclopenta[g]furo[3,4-b]quinoline-1-one (HPFQ). HPFQ is a prodigy from azapodophyllotoxin class of compounds, which have been synthesized from the perspective of improved bioactivity than its prologue podophyllotoxins. While, HPFQ has proved to be highly bioactive against most cancer cell lines with best GI values of <0.1 µM for a major number of cell lines; it also showed terrific fluorescent properties throughout the polarity scale, worthy of a promising imaging agent. The binding mechanism of HPFQ with HSA has been established by combining in vitro spectroscopic techniques, in silico molecular docking and induced fit docking (IFD). The competitive site-binding studies demonstrated that the otherwise anion-receptor sudlow site I of HSA nurtures neutral HPFQ with prudent affinity (Binding constant, K = 0.74 × 10 M). The time-resolve fluorescence studies reveal an appreciable reduction in HSA average radiative lifetime against an increase in HPFQ concentration and provided evidence for Forster's resonance energy transfer (FRET) being responsible for the dominant quenching mechanism, escorted by minor structural deformations in the backbone of protein structure. HPFQ institutes itself near Trp-214 within protein matrix, and subsequently the "hydrophobic amino acids" dominated cybotactic environment of Trp-214 experiences a reduction in the micropolarity. The allosteric modulation triggered by the stronger association of HPFQ with HSA leads towards minor deformation in secondary structure of protein. Sudlow site I of HSA proficiently embraces a favourable conformation like malleable dough to furnish space for arriving bioactive HPFQ molecule. HPFQ is also believed to administer the conformational regulation in HSA domain by affecting inter-conversion of HSA rotamers, which may prove to be an enlightening area to decode the preferable interaction between them. The juxtaposed spectroscopic research described herein is expected to embolden design of azapodophyllotoxin based anti-proliferative clinical agents for efficient in vivo bio-distribution employing HSA-centred drug delivery and administration systems.
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http://dx.doi.org/10.1016/j.bioorg.2018.11.015DOI Listing
March 2019

Realizing an Asymmetric Supercapacitor Employing Carbon Nanotubes Anchored to MnO Cathode and FeO Anode.

ACS Appl Mater Interfaces 2018 Dec 30;10(49):42484-42493. Epub 2018 Nov 30.

Solid State and Structural Chemistry Unit , Indian Institute of Science , Bengaluru 560012 , India.

A facile route to anchor pseudocapacitive materials on multiwalled carbon nanotubes (CNTs) to realize high-performance electrode materials for asymmetric supercapacitors (ASCs) is reported. The anchoring process is developed after direct decomposition of metal-hexacyanoferrate complex on the CNT surface. Transmission electron microscopy (TEM) analysis reveals that the nanoparticles (NPs) are discretely attached over the CNT surface without forming a uniform layer, thus making most of the entire NP surface available for electrochemical reactions. Accordingly, CNT-MnO nanocomposite cathode shows significantly improved capacitive performance as compared to pristine CNT electrode, validating the efficacy of designing the composite electrode. With CNT-FeO nanocomposite as the paired anode, the hybrid ASC delivers a specific capacitance of 135.2 F/g at a scan rate of 10 mV/s within a potential window of 0-1.8 V in the aqueous electrolyte and retains almost 100% of its initial capacitance after 15,000 cycles. The serially connected ASCs can power commercial light-emitting diodes (LEDs) and mobile phones, reflecting their potential in next-generation storage applications.
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http://dx.doi.org/10.1021/acsami.8b16639DOI Listing
December 2018

PRIMARY HYPERPARATHYROIDISM IN THE YOUNG: COMPARISON WITH ADULT PRIMARY HYPERPARATHYROIDISM.

Endocr Pract 2018 Dec 5;24(12):1051-1056. Epub 2018 Oct 5.

Objective: Primary hyperparathyroidism (PHPT) is relatively common among adults but rarely encountered in children and adolescents. According to the western literature, young PHPT is different from adult PHPT and is associated with more severe hypercalcemia. PHPT in the adult Indian population is different from its western counterpart. Here we present the clinical, biochemical, and surgical characteristics of young patients with PHPT treated at our tertiary care center.

Methods: PHPT patients were divided into adult (≥25 years) and young (<25 years) groups. The clinical, biochemical, hormonal, and histopathologic characteristics and treatment outcomes in the groups were compared.

Results: Out of 358 patients, 47 patients were young and 311 patients were adults. The mean ages of the groups were 19 ± 4 and 45 ± 12 years, respectively. The corresponding female-to-male ratios were 1.24:1 and 3.38:1 ( P<.05). The nature and frequency of presenting symptoms were comparable between the 2 groups. The most common symptom in young patients with PHPT was bone pain and was not significantly different from adults (57% vs. 61%, respectively). The most common symptom in adult PHPT was fatigue, which was also not significantly different from young patients (63% vs. 53%, respectively), The serum calcium, phosphate, 25-hydroxyvitamin D levels; alkaline phosphatase Z-score; and parathyroid hormone levels were comparable between the 2 groups. Parathyroid adenoma was the most common histopathologic finding, while hyperplasia was rare in both groups.

Conclusion: We observed that young PHPT is not markedly different from its adult counterpart in an Indian population.

Abbreviations: ALP = alkaline phosphatase; Ca = calcium; Cr = creatinine; iPTH = intact parathyroid hormone; 25(OH)D = 25-hydroxyvitamin D; P = phosphate; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; RR = reference range; Tc sestamibi = technetium sestamibi; USG = ultrasonography.
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http://dx.doi.org/10.4158/EP-2018-0268DOI Listing
December 2018

Evolution of the Local Structure within Chromophoric Mn-O Trigonal Bipyramids in YMnIn O with Composition.

Inorg Chem 2018 Aug 23;57(15):9012-9019. Epub 2018 Jul 23.

Solid State and Structural Chemistry Unit , Indian Institute of Science , Bengaluru 560012 , India.

We have investigated the local environment around Mn and In ions in YMnIn O chromophores to understand the origin of the intense blue color for small values of x in these solid solutions. While X-ray diffraction results provide an average description of the trigonal bipyramidal (TBP) units about Mn/In atoms with five oxygens surrounding the cation, the X-ray absorption near edge structure (XANES) as well as extended X-ray absorption fine structure (EXAFS) of these materials clearly suggest the presence of two different TBP environments, one of which is similar to MnO TBP in YMnO. EXAFS in conjunction with first-principles calculations show that replacing larger In ions by smaller Mn ones additionally gives rise to another TBP strongly distorted along the axial direction, expanding one of the axial Mn-O bonds by ∼11%. The relative fraction of these two environments changes in close agreement with the global stoichiometry with the elongated TBP, therefore, being dominant in the regime of the low Mn content. This local structural difference is responsible for the intense, but relatively narrow, absorption feature in the red-yellow region of the absorption spectrum, and hence YMnIn O appears blue for small Mn dopings. This distortion is relatively less abundant in Mn-rich compositions, and therefore, such compositions appear black, controlled by the wide absorption feature of the trigonal bipyramid coordination with Mn-O bond lengths that are essentially the same as those in YMnO, covering the entire visible range. The chromophore properties are, thus, governed by the ratio of these two MnO TBP environments, one with a characteristic optical absorption giving it a blue color and the other absorbing over the entire visible range.
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http://dx.doi.org/10.1021/acs.inorgchem.8b00997DOI Listing
August 2018

Fibrogenesis Imperfecta Ossium and Response to Human Growth Hormone: A Potential Therapy.

J Clin Endocrinol Metab 2017 05;102(5):1750-1756

Bone and Mineral Research Laboratory, Henry Ford Health System, Detroit, Michigan 48202.

Context: Fibrogenesis imperfecta ossium (FIO) is a rare bone disease manifested by generalized bone pain, fragility fractures, progressive disability, and extensive mineralization defect seen in bone biopsy specimens. The pathogenesis of the disease is unknown and currently there is no effective treatment.

Objective: To report on the effect of recombinant human growth hormone (rhGH) therapy in FIO.

Design: An observational study in two patients.

Setting: Endocrinology clinic in an academic institution.

Patients Or Other Participants: Two siblings with FIO.

Intervention(s): rhGH was administered subcutaneously at a dose of 1 U daily for 1 year.

Main Outcome Measures: Changes in clinical, biochemical, radiological, and bone histological (i.e., light and transmission electron microscopy, and histomorphometry) investigations.

Results: Except for an elevated serum alkaline phosphatase level, results of routine biochemical, hematological, and hormonal investigations were normal in both patients. Radiographs showed pseudofractures and bone scans revealed a "beheaded" tracer activity pattern (i.e., superscan without uptake in the skull). Bone biopsy specimens showed severe mineralization defect simulating osteomalacia with disorganized collagen fibril alignment. Treatment with rhGH was followed by clinical, biochemical, and radiological improvement in both the patients, with substantial improvement in the mineralization defect, most likely due to rhGH-induced improvement in collagen fibril arrangement.

Conclusion: We report on two brothers with FIO and demonstrate clinical improvement and restoration of normal bone pathology with rhGH therapy. We suggest that rhGH is a potential therapy for FIO for which no effective therapy currently exists.
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http://dx.doi.org/10.1210/jc.2016-3055DOI Listing
May 2017

The microbiology of diabetic foot infections in patients recently treated with antibiotic therapy: A prospective study from India.

J Diabetes Complications 2017 Feb 9;31(2):407-412. Epub 2016 Nov 9.

Department of Endocrinology, PGIMER, Chandigarh, 160012, India. Electronic address:

Aim: Clinicians often treat clinically infected diabetic foot ulcers without information from cultures of the wound. The results of wound cultures may also be affected by previous antibiotic therapy. Thus, we aimed to study the microbial isolates, and antimicrobial sensitivity of previously treated patients with a clinically infected DFU.

Research Design And Methods: 293 consecutive patients with clinically infected DFU on prior antimicrobial treatment within the immediate past few days for a duration greater than one week were evaluated for microbial etiology, antibiotic sensitivity and final outcomes. Appropriate tissue samples i.e. purulent drainage, soft-tissue and/ or bone were obtained for aerobic/anaerobic cultures and antimicrobial sensitivities. 71 patients with missing prior antibiotic data were excluded.

Results: 313 tissue samples obtained from 222 patients isolated 317 causative organisms. Most of the culture results from tissue specimens were mono-microbial (93.2%) compared to 37% in our previous cohort of 60 patients. Pseudomonas aeruginosa was the most common organism isolated on culture of bone (26.9%) or soft tissue (23.2%) specimen, respectively. Only 23% and 64% of P. aeruginosa isolates and 5.6% and 44% of Acinetobacter sp. were sensitive to quinolones and cephalosporins, respectively.

Conclusions: Clinically infected DFU recently treated with antibiotics have predominant monomicrobial and multi drug-resistant infection. Quinolones as an empirical antibiotic choice may not be appropriate in this setting.
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http://dx.doi.org/10.1016/j.jdiacomp.2016.11.001DOI Listing
February 2017

Unusual cause of paraparesis in a patient with Cushing's syndrome.

BMJ Case Rep 2016 Sep 21;2016. Epub 2016 Sep 21.

Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Paraparesis is a rare manifestation in patients with Cushing's syndrome and the causes include vertebral compression fracture, hypokalaemia, spinal epidural lipomatosis, paraneoplastic syndrome and metastasis to the vertebrae and spinal cord. We report an unusual cause of paraparesis due to radiation-induced myelomalacia in a patient with adrenocortical carcinoma-associated Cushing's syndrome, who are predisposed to radiation-induced injury.
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http://dx.doi.org/10.1136/bcr-2016-217304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051364PMC
September 2016

Extra-Pituitary Birth Defects May Predict Diagnosis of Congenital Hypopituitarism in a Short Child.

J Assoc Physicians India 2015 08;63(8):28-36

Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh.

Background: Extra-pituitary birth defect (EPBD) in children with congenital hypopituitarism is largely unknown.

Objective: The study aims to evaluate the incidence and pattern of EPBD in children with congenital hypopituitarism and to evaluate whether it can serve as a clue to diagnose this condition.

Patients And Methods: Retrospective analysis of hospital record of patients of short stature due to various etiology from which patients with congenital hypopituitarism with age ≥18 years were recruited for the analysis. Clinical, hormonal, radiological and ocular electrophysiological studies were done in all patients and all EPBD were noted.

Results: Twenty seven patients (79%) had multiple pituitary hormone deficiency (MPHD) of which growth hormone was universal followed by gonadotropin (62%), TSH (59%), ACTH (44%) and prolactin (12%). Nineteen patients (56%) had multiple EPBD in various combinations. Twenty three ocular abnormalities were present in 12 patients (35%). Nine patients (26%) had other associated EPBD along with ocular abnormalities while 3 had ocular abnormalities without any other associated birth defect. Skeletal defects were present in 10 patients (29.5%). On the contrary, 5 patients in the EPBD group had total 15 visual defects. The most common abnormality of the visual system were abnormal visual evoke response (VER, 18%), followed by strabismus (15%), visual acuity (VA, 12%), electroretinogram (ERG) and electrooculogram (EOG) 8% each and visual field defect 6%. There was a trend towards early age at presentation with EPBD.

Conclusions: Presence of EPBD in a short child is a sensitive marker to diagnose congenital hypopituitarism. Subtle abnormalities of visual pathway without absent septum pellucidum or midline brain defects were common.
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August 2015

An infant with diabetes mellitus: Is it always T1DM?

Diabetes Res Clin Pract 2017 Mar 28;125:62-64. Epub 2016 Jul 28.

Dept. of Endocrinology, PGIMER, Chandigarh, India. Electronic address:

Here we describe a 2month old infant with neonatal diabetes mellitus (NDM) who was initially misdiagnosed to have T1DM and initiated on insulin. He was found to have a novel heterozygous mutation Arg992Cys in ABCC 8 gene and successfully switched to oral anti-diabetic drug.
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http://dx.doi.org/10.1016/j.diabres.2016.07.014DOI Listing
March 2017

Spontaneous diabetic myonecrosis: report of four cases from a tertiary care institute.

Endocrinol Diabetes Metab Case Rep 2015 1;2015:150003. Epub 2015 May 1.

Department of Endocrinology , Post Graduate Institute of Medical Education and Research , Chandigarh, 160012 , India.

Unlabelled: Spontaneous diabetic muscle infarction (DMI) is a rare and under diagnosed complication of diabetes mellitus. Clinically it presents with acute to subacute onset swelling, pain and tenderness of muscle(s) without systemic manifestations. MRI is helpful in diagnosis, exclusion of other causes and for localization of affected muscle for biopsy in atypical cases. Muscles of the thighs are commonly affected in diabetic myonecrosis (DMN). Here we present the summary of four cases seen in the last 3 years in a tertiary care centre with simultaneous or sequential involvement of multiple groups of muscles or involvement of uncommon sites. All these patients had advanced duration of diabetes with microvascular complications and poor glycemic control. Conservative management including rest and analgesics is the treatment of choice. Short-term prognosis is good but there may be recurrence.

Learning Points: A high index of suspicion is required for the diagnosis of DMN which can avoid inadvertent use of antibiotics.Acute-subacute onset severe focal muscle pain in the absence of systemic symptoms in a female patient with long-standing diabetes with microvascular complications suggests DMI.MRI is the most sensitive test for diagnosis.Muscle biopsy should be reserved for atypical cases.Conservative management including rest and analgesics has good outcome.Improvement usually occurs within 6-8 weeks, but there may be recurrence.
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http://dx.doi.org/10.1530/EDM-15-0003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482157PMC
June 2015

Coexistence of two sclerotic bone diseases manifesting as spondyloarthropathy: Double trouble.

Bone Rep 2015 Jun 15;2:89-91. Epub 2015 May 15.

Dept. of Endocrinology, PGIMER, Chandigarh, India.

Hypoparathyroidism and fluorosis are two distinct sclerotic bone diseases. Both have high BMD but they behave differently. Fluorosis causes secondary hyperparathyroidism and has been reported to cause renal dysfunction. Here we discuss a case that coincidentally had both the disorders and their interaction.
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http://dx.doi.org/10.1016/j.bonr.2015.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365166PMC
June 2015

Efficient solid-state light-emitting CuCdS nanocrystals synthesized in air.

Angew Chem Int Ed Engl 2015 Feb 16;54(9):2643-8. Epub 2015 Jan 16.

Centre for Advanced Materials, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032 (India).

Semiconductor nanocrystals (NCs) possess high photoluminescence (PL) typically in the solution phase. In contrary, PL rapidly quenches in the solid state. Efficient solid state luminescence can be achieved by inducing a large Stokes shift. Here we report on a novel synthesis of compositionally controlled CuCdS NCs in air avoiding the usual complexity of using inert atmosphere. These NCs show long-range color tunability over the entire visible range with a remarkable Stokes shift up to about 1.25 eV. Overcoating the NCs leads to a high solid-state PL quantum yield (QY) of ca. 55% measured by using an integrating sphere. Unique charge carrier recombination mechanisms have been recognized from the NCs, which are correlated to the internal NC structure probed by using extended X-ray absorption fine structure (EXAFS) spectroscopy. EXAFS measurements show a Cu-rich surface and Cd-rich interior with 46% Cu(I) being randomly distributed within 84% of the NC volume creating additional transition states for PL. Color-tunable solid-state luminescence remains stable in air enabling fabrication of light-emitting diodes (LEDs).
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http://dx.doi.org/10.1002/anie.201409518DOI Listing
February 2015