Areas Of Modern Research Research Articles

Effect of anticancer therapy on Tn antigen exposure on the leucocyte membranes in patients with leukemia

Tn-antigen (Thomsen-nouvelle antigen) is tumor-associated carbohydrate antigen with only one GalNAc residue attached to serine or threonine of polypeptide chain. There is not enough data about the expression of this glycotope in hematologic processes. But the correlations between increasing Tn-antigen expression on the cell surface and tumor growth progression, invasion, and activation of cell migration are well known. Therefore, the currently important area of modern research is studying of the impact of anticancer therapy by expression of this carbohydrate antigen in the onco-proliferative process. There are two types of cytostatic therapies in clinical hospitals of Ukraine: COP-therapy (cyclophosphamide, vincristine, prednisone) and FC-therapy (fludarabine, cyclophosphamide), which are the most popular due to their effectiveness and low price. The aim of our study was to investigate Tn-antigen exposure on the surface of lymphocytes, monocytes and granulocytes in polycythemia vera and subleukemic myelosis; to examine the influence of COP- and FC-therapies on Tn-antigen exponation in patients with chronic lymphocytic leukemia. The objects of the study were blood cells of patients with chronic lymphocytic leukemia (n = 25), polycythemia vera (n = 15) and subleukemic myelosis (n = 15) aged 58–66 years. Healthy hematologic volunteers (n = 15) aged 55 to 65 years were in the control group. Lymphocytes of patients with chronic lymphocytic leukemia (n = 25) were also studied after the chemotherapy treatment of patients divided into two groups: those who took COP-therapy (n = 13); and those who treated with FC-therapy (n = 12). Tn-antigen exposure on lymphocytes, monocytes and granulocytes was investigated by Beckman Сoulter EPICS flow cytometer with primary monoclonal Tn-antigen anybodies (Institute of Immunology, Moscow, Russia) and secondary fluorescein isothiocyanate labeled antybodies (Millipore, USA). The number of dead cells was monitored by binding them with propidium iodide. The result was analyzed with FC Express. According to our data, Tn-antigen exposure was not detected on the surface of blood cells (lymphocytes, monocytes and granulocytes) in the control group and in patients with polycythemia vera and subleukemic myelosis. Nevertheless, Tn-antigen was identified on the surface of more than 80% of lymphocytes in chronic lymphocytic leukemia patients. The intensity of this tumor-associated antigen exposure on lymphocytes membrane was 100 times higher compared with that in normal lymphocytes. In chronic lymphocytic leukemia patients after COP-treatment the number of lymphocytes with surface Tn-antigen was equal to 28,1 ± 0,8%, and after FC-treatment it decreased to 9,5 ± 0,5%. Moreover, positive effect of cytotoxic therapy used in treatment of patients with chronic lymphocytic leukemia on intensity of Tn-antigen exposure on the surface of lymphocytes was shown. FC-therapy (fludarabine, cyclophosphamide) is more effective; compared with the data prior to this treatment it 40 times reduced the relevant index. Therefore, it can be applied in Ukraine for chemotherapeutic treatment schemes effective against Tn-antigen.

Mechanically Interlocked DNA nanostructures for Functional Devices

CONSPECTUS: Self-assembled functional DNA oligonucleotide based architectures represent highly promising candidates for the creation of nanoscale devices. The field of DNA nanotechnology has emerged to a high level of maturity and currently constitutes one of the most dynamic, creative, and exciting modern research areas. The transformation from structural DNA nanotechnology to functional DNA architectures is already taking place with tremendous pace. Particularly the advent of DNA origami technology has propelled DNA nanotechnology forward. DNA origami provided a versatile method for precisely aligning structural and functional DNA modules in two and three dimensions, thereby serving as a means for constructing scaffolds and chassis required for the precise orchestration of multiple functional DNA architectures. Key modules of these will contain interlocked nanomechanical components made of DNA. The mechanical interlocking allows for performing highly specific and controlled motion, by reducing the dimensionality of diffusion-controlled processes without restrictions in motional flexibility. Examples for nanoscale interlocked DNA architectures illustrate how elementary functional units of future nanomachines can be designed and realized, and show what role interlocked DNA architectures may play in this endeavor. Functional supramolecular systems, in general, and nanomachinery, in particular, self-organize into architectures that reflect different levels of complexity with respect to their function, their arrangement in the second and third dimension, their suitability for different purposes, and their functional interplay. Toward this goal, DNA nanotechnology and especially the DNA origami technology provide opportunities for nanomechanics, nanorobotics, and nanomachines. In this Account, we address approaches that apply to the construction of interlocked DNA nanostructures, drawing largely form our own contributions to interlocked architectures based on double-stranded (ds) circular geometries, and describe progress, opportunities, and challenges in rotaxanes and pseudorotaxanes made of dsDNA. Operating nanomechanical devices in a reliable and repetitive fashion requires methods for switching movable parts in DNA nanostructures from one state to another. An important issue is the orthogonality of switches that allow for operating different parts in parallel under spatiotemporal control. A variety of switching methods have been applied to switch individual components in interlocked DNA nanostructures like rotaxanes and catenanes. They are based on toehold, light, pseudocomplementary peptide nucleic acids (pcPNAs), and others. The key issues discussed here illustrate our perspective on the future prospects of interlocked DNA-based devices and the challenges that lay ahead.

Quorum quenching and antibacterial activity of silver nanoparticles synthesized from <i>Sargassum polyphyllum</i>

Development of efficient methodology for the green synthesis of silver nanoparticles using marine algae is a modern area of research in the field of phyconanotechnology. In this regard, the present study deals with green synthesis of silver nanoparticles (AgNPs) by using aqueous extracts of marine brown seaweed Sargassum polyphyllum. UV-visible spectral analysis reveals the formation of AgNPs by showing absorption maximum at 420 nm wavelength and SEM analysis clearly elucidate the polydispersed structure of AgNPs without aggregation and ranged in size from 37-43 nm. X-ray Diffraction pattern confirmed the AgNPs crystalline personality. The synthesized AgNPs showed more enduring antibacterial activity against test bacterial pathogens. Furthermore, the synthesized AgNPs exhibited varying level of inhibition of violacein production and swarming motility. In the near future, silver nanoparticles can be extremely useful in clinical medicine as an alternative method for the treatment of wound infection.

Mixtures of spatial spline regressions for clustering and classification

Classification and clustering of functional data arise in many areas of modern research. Currently, techniques for performing such tasks have concentrated on applications to univariate functions. Such techniques can be extended to the domain of classifying and clustering bivariate functions (i.e. surfaces) over rectangular domains. This is achieved by combining the current techniques in spatial spline regression (SSR) with finite mixture models and mixed-effects models. As a result, three novel techniques have been developed: spatial spline mixed models (SSMM) for fitting populations of surfaces, mixtures of SSR (MSSR) for clustering surfaces, and MSSR discriminant analysis (MSSRDA) for classification of surfaces. Through simulations and applications to problems in handwritten character recognition, it is shown that SSMM, MSSR, and MSSRDA are effective in performing their desired tasks. It is also shown that in the context of handwritten character recognition, MSSR and MSSRDA are comparable to established methods, and are able to outperform competing approaches in missing-data situations.

The journey of l-tartaric acid in the world of enantiomerically pure bis- and trisadducts of C60 with the inherently chiral trans-3 and all-trans-3 addition patterns

Inherently chiral multi-adducts of [60]fullerene represent unique chiral molecular tectons featuring fascinating optoelectronic properties. Herein we discuss the most recent progress in the synthesis of enantiomerically pure bis- and trisadducts of C60 with the inherently chiral trans-3 and all-trans-3 addition patterns utilizing cyclo-[n]-malonate tethers derived from (-)-dimethyl-2,3-O-isopropylidene-L-tartrate. Some future perspectives regarding the investigation of these chiral building blocks in modern areas of research are discussed.

Structural Basis for Modulation of a GPCR by Allosteric Drugs

The design of G protein-coupled receptor (GPCR) allosteric modulators, an active area of modern pharmaceutical research, has proven challenging because neither the binding modes nor the molecular mechanisms of such drugs are known. Here we determined binding sites, bound conformations, and specific drug-receptor interactions for several allosteric modulators of the M2 muscarinic acetylcholine receptor, a prototypical Family A GPCR, using atomic-level simulations in which the modulators spontaneously associated with the receptor (Nature, in press). Despite substantial structural diversity, all modulators formed cation-π interactions with clusters of aromatic residues in the receptor extracellular vestibule, ∼15 A from the classical, “orthosteric” ligand-binding site. We validated the observed modulator binding modes through radioligand binding experiments on receptor mutants designed, on the basis of our simulations, to either increase or decrease modulator affinity. Simulations also revealed mechanisms that contribute to positive and negative allosteric modulation of classical ligand binding, including coupled conformational changes of the two binding sites and electrostatic interactions between ligands in these sites. These observations enabled the design of chemical modifications that significantly altered a modulator's allosteric effects. Our findings thus provide a structural basis for the rational design of allosteric modulators targeting muscarinic and possibly other GPCRs.

SURVEY AND ANALYSIS OF UNDERGROUND WATER OF FIVE VILLAGES OF TRIPURA, INDIA

The present study emphasizes on the survey and asse ssment of groundwater quality, sources of ground wa ter contamination, variation of groundwater quality and which will be further pu rified with the use of nanomaterials. The bases for groundwater quality assessment are underground water (tube-well) and re presentative monitoring network enabling determinat ion of chemical status of the underground water (tube-well). For this study, water samples were collected from 5 tube wells repr esenting the area of 5 villages (Golaghati, Takarjala, Jampui, Mandwi, and Simna) o f Tripura (India). The water samples were analyzed for physico -chemical parameters like Total Dissolved Solid, Total Hardne ss, Iron, Chloride, Calcium, Magnesium etc using st andard techniques in the laboratory and compared with the standards. The res ults obtained in this study and the Association rul es will be helpful for monitoring and managing presence of heavy metals in underground water in the modern research area in t erms of water quality. The parameters: pH, TDS, Total hardness and content of Iron, Chloride, Calcium, Magnesium and BOD were stu died and compared with the standard values prescribed by ICMR, WHO, APHA aThe present investigation revealed that the quality of water of a source slightly varies from area to area tube wells but was found that the underground water samples a re fit for drinking and utility purpose.

Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs

The design of G-protein-coupled receptor (GPCR) allosteric modulators, an active area of modern pharmaceutical research, has proved challenging because neither the binding modes nor the molecular mechanisms of such drugs are known. Here we determine binding sites, bound conformations and specific drug-receptor interactions for several allosteric modulators of the M2 muscarinic acetylcholine receptor (M2 receptor), a prototypical family A GPCR, using atomic-level simulations in which the modulators spontaneously associate with the receptor. Despite substantial structural diversity, all modulators form cation-π interactions with clusters of aromatic residues in the receptor extracellular vestibule, approximately 15 Å from the classical, 'orthosteric' ligand-binding site. We validate the observed modulator binding modes through radioligand binding experiments on receptor mutants designed, on the basis of our simulations, either to increase or to decrease modulator affinity. Simulations also revealed mechanisms that contribute to positive and negative allosteric modulation of classical ligand binding, including coupled conformational changes of the two binding sites and electrostatic interactions between ligands in these sites. These observations enabled the design of chemical modifications that substantially alter a modulator's allosteric effects. Our findings thus provide a structural basis for the rational design of allosteric modulators targeting muscarinic and possibly other GPCRs.

A robust multimedia authentication and restoration scheme in digital photography

Image authentication and restoration is an important area of modern research. In digital photography, copyright protection is very crucial. Visible signatures distract from the meaning of the photograph as well as they are easy to be removed by using advanced softwares. Invisible watermarks provide protection, offer a better look to photographs than visible watermarking, and prevent the photographs from unauthorized manipulations. A robust multiple watermarking scheme is required which could invisibly protect the content and also should survive the manipulations for later verification and restoration. In this paper, a robust and imperceptible multimedia authentication and restoration scheme is proposed. The security of Advanced Encryption Standard (AES) is utilized to make an encrypted watermark. The encrypted watermark is then embedded into photographs in the salient regions by proposed Feature-Closest Point Transform (F-CPT) algorithm. The second watermark is generated by wavelet decomposition and embedded in the second and third level wavelet sub-bands of the cover photographs. Several security attacks are performed e.g. noise attack, compression attack, resizing attack, rotation attack, collage attack, and cropping attack on multiple watermarked photographs to examine the system robustness by normalized cross correlation (NCC) for retrieved authentication watermarks. Result of PSNR, MSE, and SSIM show the high imperceptibility of our technique and aesthetic score (AS) shows the aesthetic quality of watermarked photographs (WPs).

Adaptive Input Design for Identification of Output Error Model with Constrained Output

Optimal input design for system identification is an area of intensive modern research. This paper considers the identification of output error (OE) model, for the case of constrained output variance. The constraint plays a very important role in the process industry, in the reduction of degradation of product quality. In this paper, it is shown, in the form of a theorem, that the optimal input signal, with constrained output, is achieved by a minimum variance controller together with a stochastic reference. The key problem is that the optimal input depends on the system parameters to be identified. In order to overcome this problem, a two-stage adaptive procedure is proposed: obtaining an initial model using PRBS as input signal; application of adaptive minimum variance controller together with the stochastic variable reference, in order to generate input signals for system identification. Theoretical results are illustrated by simulations.

Oxidative stress induced by inorganic nanoparticles in bacteria and aquatic microalgae – state of the art and knowledge gaps

Nanotechnology has revolutionised many areas of modern life, technology and research, which is reflected in the steadily increasing global demand for and consumption of engineered nanomaterials and the inevitable increase of their release into the environment by human activity. The overall long-term impact of engineered nanomaterials on ecosystems is still unknown. Various inorganic nanoparticles have been found to exhibit bactericidal properties and cause growth inhibition in model aquatic microalgae, but the mechanisms of toxicity are not yet fully understood. The causal link between particle properties and biological effects or reactive oxygen species generation is not well established and represents the most eminent quest of nanoecotoxicological investigation. In this review, the current mechanistic understanding of the toxicity of inorganic metal and metal oxide engineered nanomaterials towards bacterial and aquatic microalgal model organisms based on the paradigm of oxidative stress is presented along with a detailed compilation of available literature on the major toxicity factors and research methods.

Editorial for the special issue on: SUNOVA 2012

Statistical methods and models assuming the existence of not directly observable or “latent” variables are extensively used in every modern research area. This Special Issue, inspired by the Workshop “ Statistics with Unobservable Variables ” (SUNOVA) held at the University of Brescia as part of the activities of the Research Center “ Data Methods and Systems ” on May 15, 2012, highlights the opportunities offered by some of the most advanced statistical approaches that make use of these types of variables. The short papers submitted by the authors adopt different approaches, models and algorithms to “discover” latent variables (Structural Equation and Factor models, Rasch and Item Response models, Topic models, Non-symmetric CA, Non-linear PCA, Partial Least Squares-PM), with applications in various research fields (healthcare, psychometrics, education, finance, management and bibliometrics). It was a pleasure for us to have the opportunity to read these interesting studies, and we wish to express our thanks to all the authors and reviewers that have made possible this special issue dedicated to the Workshop SUNOVA 2012.

Chronic Lymphocytic Leukemia: Inception to Cure: Are We There?

There have been remarkable advances in our understanding of the biology and therapeutics of chronic lymphocytic leukemia. B cell receptor signaling and micro-environment in CLL biology have been the most modern areas of research. In CLL therapeutics, we have come a long way from alkylating agents to chemo-immunotherapy. Despite this there remain significant lacunae in the disease biology that has hindered our quest to achieve the ultimate in CLL: Cure. This review aims to summarize the past, present and future in the biology and treatment of CLL.

“Oh yes, oh yes, these are the atoms!” A Personal Recollection from the Times of the Invention of the STM

The scanning tunneling microscope, invented and developed in the 1980s in the IBM research laboratory in Rüschlikon, has become the dominent scientific tool in surface science and together with its younger brother the atomic force microscope, is widely used also in many other modern research areas. This account contains very personal anecdotal memories from a colleague who worked in a neighboring lab in Rüschlikon describing some events at the periphery of the development of this ingenious instrument.

NETWORKS AND 1/f NOISE

Complex networks form one of the most challenging areas of modern research overarching the traditional scientific disciplines. Of particular importance is the manner in which information is shuttled back and forth between such networks, and whether or not there exists general principles that guide the flow of information. Herein, we identify Wiener's rule, which conjectures how information is transfered in an information-dominated process. Moreover, we show that this rule is a consequence of the Principle of Complexity Management (PCM) that determines the information exchange between complex networks. A consequence of the PCM is that the maximum information transfer occurs at a 1/f noise resonance. The information transfer between two complex networks is also determined by direct numerical calculation of a master equation model of network dynamics using interacting two-state elements, the decision-making model (DMM). The DMM generates phase transitions and on a two-dimensional lattice, reduces to the Ising model in an appropriate limit. The computations using the DMM suggest that the inverse power laws of links and survival probability are not necessarily related.

Improving Robot-Human Communication by Integrating Visual Attention and Auditory Localization Using a Biologically Inspired Model of Superior Colliculus

Effective agent communication is always been an important modern area of research. This paper focuses on achieving greater precision in common by improving agent-human communication with the help of visual attention and auditory localization based on a simple model of the superior colliculus in the human brain system. The model receives individual visual and auditory sensory stimuli and combines them to generate an integrated stimulus predicting the location of the sound source. This integrated stimulus is used to generate a motor saccade of the visual system to attend to the sound. The computational model is based on a neural network approach with learning and is explored in experiments reflecting varied conditions to determine whether it mimes the performance of superior colliculus in auditory and visual stimuli integration. Finally with a evaluation strategy carried between unimodal and multimodal data, the efficiency of the computational model of Superior Colliculus is determined. Performance of the neural network based computational model has proven effective in terms of learning, the better performance of the integrated response over unimodal response and providing a realistic communication experience.

QSPR studies on aqueous solubilities of drug-like compounds.

A rapidly growing area of modern pharmaceutical research is the prediction of aqueous solubility of drug-sized compounds from their molecular structures. There exist many different reasons for considering this physico-chemical property as a key parameter: the design of novel entities with adequate aqueous solubility brings many advantages to preclinical and clinical research and development, allowing improvement of the Absorption, Distribution, Metabolization, and Elimination/Toxicity profile and “screenability” of drug candidates in High Throughput Screening techniques. This work compiles recent QSPR linear models established by our research group devoted to the quantification of aqueous solubilities and their comparison to previous research on the topic.

New QSPR study for the prediction of aqueous solubility of drug-like compounds

Solubility has become one of the key physicochemical screens at early stages of the drug development process. Solubility prediction through Quantitative Structure–Property Relationships (QSPR) modeling is a growing area of modern pharmaceutical research, being compatible with both High Throughput Screening technologies and limited compound availability characteristic of early stages of drug development. We resort to the QSPR theory for analyzing the aqueous solubility exhibited by 145 diverse drug-like organic compounds (0.781 being the average Tanimoto distances between all possible pairs of compounds in the training set). An accurate and generally applicable model is derived, consisting on a linear regression equation that involves three DRAGON molecular descriptors selected from more than a thousand available. Alternatively, we apply the linear QSPR to other 21 commonly employed validation compounds, leading to solubility estimations that compare fairly well with the performance achieved by previously reported Group Contribution Methods.

The Bioterrorism Threat and Dual-use Biotechnological Research: An Israeli Perspective

Israel has a long history of concern with chemical and biological threats, since several hostile states in the Middle East are likely to possess such weapons. The Twin-Tower terrorist attacks and Anthrax envelope scares of 2001 were a watershed for public perceptions of the threat of unconventional terror in general and of biological terror in particular. New advances in biotechnology will only increase the ability of terrorists to exploit the burgeoning availability of related information to develop ever-more destructive bioweapons. Many areas of modern biological research are unavoidably dual-use by nature. They thus have a great potential for both help and harm; and facilitating the former while preventing the latter remains a serious challenge to researchers and governments alike. This article addresses how Israel might best (1) prevent hostile elements from obtaining, from Israel's biological research system, materials, information and technologies that might facilitate their carrying out a biological attack, while (2) continuing to promote academic openness, excellence and other hallmarks of that system. This important and sensitive issue was assessed by a special national committee, and their recommendations are presented and discussed. One particularly innovative element is the restructuring and use of Israel's extensive biosafety system to also address biosecurity goals, with minimal disruption or delay.

Analytical tools for the nano world

Nanotechnology and nanoscience are very important areas of modern research. They are supposed to give us judicious control over the properties of matter at the nanoscale (i.e., lengths of well below 1 μm in at least two dimensions). Nano objects include structures such as subcellular compartments, “molecular machines” and small biological objects, nanocomposites, and components of molecular electronics. However, there is currently a lack of chemical diagnostics and characterization methods for these nano objects and nanoscale structures, particularly methods for characterizing their molecular compositions. Established methods for studying matter with nanoscale lateral resolution, such as atomic force microscopy (AFM), scanning tunneling microscopy (STM), and scanning electron microscopy (SEM), typically give very little or no chemical information. Some exceptions exist—for example derivatized AFM tips that can be used for chemical recognition. In general, however, only the shape of a nanostructure, its surface topography, and its local electric properties can be measured, albeit in many cases with excellent spatial resolution, down to the atomic scale. However, with the advent of nanotechnology and nanoscience, the need for chemical and in particular molecular analysis has become urgent. Several new approaches to spectroscopic observation and imaging with nanometer-scale resolution have appeared recently, and will continue to set trends in the fields of nanoscience and nanotechnology. Scanning near-field optical microscopy (SNOM), the “optical cousin” of STM and AFM, emerged in the 1980s [1]. Standard aperture SNOM works by guiding light from a laser into an optical fiber whose tip is sharpened and metallized on the outside such that only a very small aperture (diameter ≈50 nm) passes laser light. If brought close to the object under investigation (within a few nm, i.e., into the optical near-field), this nanometer light source can be used to illuminate a spot on a sample that is considerably smaller than the optical diffraction limit. In order to obtain a high-resolution optical image of the sample, the SNOM tip is scanned over the sample surface with nanometer accuracy, using piezo elements for motion control. SNOM observation was initially restricted to fluorescence [2], but was later extended to Raman spectroscopy [3] and even to laser ablation mass spectrometry [4, 5]. One of the main limitations of SNOM is its optical throughput when using very small apertures. This limits both the achievable spatial resolution and the optical brightness of SNOM nano light sources. A way to circumvent this limitation is to use apertureless near-field methods, such as tip-enhanced Raman scattering (TERS). In this case, Raman scattering is amplified by the presence of a metallic nanoparticle brought close to the sample, using an AFM cantilever for example. Conceptually, this is an inversion of the geometry used in surface-enhanced Raman scattering (SERS). The advantage of this approach is that the sample can be illuminated using conventional optics, avoiding the much lower transmission of an aperture SNOM probe. Such apertureless or “tip-enhanced” nearfield spectroscopy experiments have been realized using coated AFM tips or sharpened metal tips, and are used for Anal Bioanal Chem (2008) 390:215–221 DOI 10.1007/s00216-007-1640-1