Thalappil Pradeep

Bio: Thalappil Pradeep is an academic researcher from Indian Institute of Technology Madras. The author has contributed to research in topics: Cluster (physics) & Mass spectrometry. The author has an hindex of 76, co-authored 581 publications receiving 24664 citations. Previous affiliations of Thalappil Pradeep include DST Systems & Lawrence Berkeley National Laboratory.

Monitoring of changes in lipid profiles during PLK1 knockdown in cancer cells using DESI MS

Abstract: The importance of the polo-like kinase 1 (PLK1) gene is increasing substantially both as a biomarker and as a target for highly specific cancer therapy. This is due to its involvement in multiple points of cell progression and carcinogenesis. PLK1 inhibitors’ efficacy in treating human cancers has been limited due to the lack of a specific targeting strategy. Here, we describe a method of targeted downregulation of PLK1 in cancer cells and the concomitant rapid detection of surface lipidomic perturbations using desorption electrospray ionization mass spectrometry (DESI MS). The efficient delivery of siRNA targeting PLK1 gene selectively to the cancer cells is achieved by targeting overexpressed cell surface epithelial cell adhesion molecule (EpCAM) by the EpDT3 aptamer. The chimeric aptamer (EpDT3-siPLK1) showed the knockdown of PLK1 gene expression and PLK1 protein levels by quantitative PCR and western blotting, respectively. The abundant surface lipids, phosphatidylcholines (PCs), such as PC(32:1) (m/z 754.6), PC(34:1) (m/z 782.6), and PC(36:2) (m/z 808.6), were highly expressed in MCF-7 and WERI-RB1 cancer cells compared to normal MIO-M1 cells and they were observed using DESI MS. These overexpressed cell surface lipids in the cancer cells were downregulated upon the treatment of EpDT3-siPLK1 chimera indicating a novel role of PLK1 to regulate surface lipid expression in addition to the efficient selective cancer targeting ability. Our results indicate that DESI MS has a potential ability to rapidly monitor aptamer-mediated cancer therapy and accelerate the drug discovery process.

Interaction of Acetonitrile with Alcohols at Cryogenic Temperatures

Abstract: Temperature-dependent interaction of acetonitrile with methanol and ethanol, as codeposited and sequentially deposited films, was studied in the 10–130 K window, in ultra high vacuum. Films in the range of 50–100 monolayers were investigated using temperature-dependent reflection–absorption infrared spectroscopy (RAIRS), Cs+ ion scattering mass spectrometry, and temperature-programmed desorption (TPD). Acetonitrile interacts with methanol and ethanol through intermolecular hydrogen bonding. When a codeposited system was annealed, acetonitrile underwent a phase segregation at 110 K, and large changes in the infrared spectrum were observed. The OH stretching of methanol gave two peaks characteristic of the change to the α-phase of methanol, while ethanol gave three peaks at the same temperature. The surface composition of the systems probed by 40 eV Cs+ scattering showed that both the alcohols and the acetonitrile were of equal intensity below 110 K, while above 110 K the intensity of the latter went down s...

Formation of H2+ by Ultra-Low-Energy Collisions of Protons with Water Ice Surfaces

Abstract: The molecular ion of dihydrogen (H2 + ) is produced by 1 eV collisions of protons (H + ) onamorphous water ice surfaces.The reaction is also observed on crystalline ice surfaces, but with lower efficiency. Collisions of D + on amorphous H2O and D2O ices yield D2 + on the former, subsequent to isotope exchange on the H2O surface. Ultra-low-energy collision-induced dihydrogen ion production is also observed from alkanol surfaces, with decreasing efficiency asthe alkyl chainlength increases.Thereis nocorrespond- ing reaction on solid hexane. This endothermic reaction, with implications for interstellar chemistry and plasma etching processes, is proposed to occur as a resultofstabilizationoftheotherreactionproduct,ahydroxylradical(OH  ),on water surfaces through hydrogen-bonding interactions with the surface. These results point to an interesting chemistry involving ultra-low-energy ions on molecular solids.

Ambient electrospray deposition Raman spectroscopy (AESD RS) using soft landed preformed silver nanoparticles for rapid and sensitive analysis

Abstract: We introduce a technique called ambient electrospray deposition Raman spectroscopy (AESD RS) for rapid and sensitive surface-enhanced Raman scattering (SERS) based detection of analytes using a miniature Raman spectrometer. Using electrospray, soft landing of preformed silver nanoparticles (AgNPs) was performed for 30-40 seconds for different concentrations of analytes deposited on conducting glass slides. Using AESD RS, SERS signals were collected within 4-6 minutes, including sample preparation. Transmission electron microscopy (TEM) and dark-field microscopy (DFM) were used to characterize the preformed AgNPs before and after electrospray. We achieved the nanomolar and micromolar detection of p-mercaptobenzoic acid (p-MBA) and 2,4-dinitrotoluene (2,4-DNT), respectively. In this work, 0.3 μL of preformed AgNPs were used, which is ∼33 times less in volume than the quantity needed for conventional SERS. Quantitation of unknown concentration of analytes was also possible. A similar amount of electrosprayed AgNPs was utilized to characterize Escherichia coli (E. coli) bacteria of different concentrations. Viability of bacteria was tested using fluorescence microscopic imaging. Besides reduced analysis time and improved reproducibility of the data in every analysis, which is generally difficult in SERS, the amount of AgNPs required is an order of magnitude lower in this method. This method could also be used to probe the real-time changes in molecular and biological species under ambient conditions.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

Fast parallel algorithms for short-range molecular dynamics

Abstract: Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Gold nanoparticles in chemical and biological sensing.

Abstract: Detection of chemical and biological agents plays a fundamental role in biomedical, forensic and environmental sciences1–4 as well as in anti bioterrorism applications.5–7 The development of highly sensitive, cost effective, miniature sensors is therefore in high demand which requires advanced technology coupled with fundamental knowledge in chemistry, biology and material sciences.8–13 In general, sensors feature two functional components: a recognition element to provide selective/specific binding with the target analytes and a transducer component for signaling the binding event. An efficient sensor relies heavily on these two essential components for the recognition process in terms of response time, signal to noise (S/N) ratio, selectivity and limits of detection (LOD).14,15 Therefore, designing sensors with higher efficacy depends on the development of novel materials to improve both the recognition and transduction processes. Nanomaterials feature unique physicochemical properties that can be of great utility in creating new recognition and transduction processes for chemical and biological sensors15–27 as well as improving the S/N ratio by miniaturization of the sensor elements.28 Gold nanoparticles (AuNPs) possess distinct physical and chemical attributes that make them excellent scaffolds for the fabrication of novel chemical and biological sensors (Figure 1).29–36 First, AuNPs can be synthesized in a straightforward manner and can be made highly stable. Second, they possess unique optoelectronic properties. Third, they provide high surface-to-volume ratio with excellent biocompatibility using appropriate ligands.30 Fourth, these properties of AuNPs can be readily tuned varying their size, shape and the surrounding chemical environment. For example, the binding event between recognition element and the analyte can alter physicochemical properties of transducer AuNPs, such as plasmon resonance absorption, conductivity, redox behavior, etc. that in turn can generate a detectable response signal. Finally, AuNPs offer a suitable platform for multi-functionalization with a wide range of organic or biological ligands for the selective binding and detection of small molecules and biological targets.30–32,36 Each of these attributes of AuNPs has allowed researchers to develop novel sensing strategies with improved sensitivity, stability and selectivity. In the last decade of research, the advent of AuNP as a sensory element provided us a broad spectrum of innovative approaches for the detection of metal ions, small molecules, proteins, nucleic acids, malignant cells, etc. in a rapid and efficient manner.37 Figure 1 Physical properties of AuNPs and schematic illustration of an AuNP-based detection system. In this current review, we have highlighted the several synthetic routes and properties of AuNPs that make them excellent probes for different sensing strategies. Furthermore, we will discuss various sensing strategies and major advances in the last two decades of research utilizing AuNPs in the detection of variety of target analytes including metal ions, organic molecules, proteins, nucleic acids, and microorganisms.