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The noncanonical conformations within the genomes of viral pathogens is of significant diagnostic value, due to their unique secondary structures and interactions with specific fluorogenic molecules. In particular, adaptation of the G-quadruplex (GQ) conformation by the specific gene sequence leads to distinct topological features, resulting in unique binding sites that are crucial for the selective recognition of human immunodeficiency virus (HIV) by small molecules. Leveraging the selective fluorescence response of a benzobisthiazole-based fluorogenic probe to the LTR-III GQ target, we developed a GQ-based diagnostic platform for HIV detection. The successful fluorescence recognition of an amplified 176-nucleotide genomic segment harboring the LTR-III GQ, facilitated by pH-controlled GQ-targeted reliable conformational polymorphism (GQ-RCP), validates this method as an effective GQ-topology-targeted diagnostic tool for HIV.

Tracheostomy is commonly performed life saving procedure. Organophosphorus compound poisoning is a very common emergency encountered in rural area where major population consists of agricultural workers. Ideal timing of tracheostomy is still controversial. Aim of the study is to assess the advantage of performing early (48 h-7 days) versus late tracheostomy (8-15 days) with regard to weaning from a ventilator, complications and length of hospital stay. This is a comparative retrospective interventional study in which 100 patients of organophosphorus poisoning who underwent tracheostomy during hospital stay due to prolonged intubation were analyzed. Study subjects were divided into two groups. Each group constitute of 50 patients each. Group A: Early tracheostomy (48 h-7 days) and Group B: Late tracheostomy (8-15 days). Early tracheostomy required a shorter duration of mechanical ventilator support (4-5 days) when compared to late tracheostomy (5-8 days), p  < 0.05 and early tracheostomy facilitate early weaning. There was high incidence of complications in late tracheostomy group as compare to early tracheostomy group. Duration of hospital stay was also longer in Group B (mean 40 days) as compare to Group A (mean 32 days) with p  < 0.05. We concluded that, early tracheostomy was associated with shorter duration of mechanical ventilator support, it helps for early weaning, shorted intensive care unit and hospital stay as compare to late tracheostomy., Competing Interests: Conflict of interestAll author declare that they have no conflict of interest., (© Association of Otolaryngologists of India 2017.)

A unique strategy for scavenging free radicals in situ on exposure to gamma irradiation in polyethylene (PE) nanocomposites is presented. Blends of ultra-high molecular weight PE and linear low-density PE (PEB) and their nanocomposites with graphene (GPEB) were prepared by melt mixing to develop materials for biomedical implants. The effect of gamma irradiation on the microstructure and mechanical properties was systematically investigated. The neat blend and the nanocomposite were subjected to gamma-ray irradiation in order to improve the interfacial adhesion between PE and graphene sheets. Structural and thermal characterization revealed that irradiation induced crosslinking and increased the crystallinity of the polymer blend. The presence of graphene further enhanced the crystallinity via crosslinks between the polymer matrix and the filler on irradiation. Graphene was found to scavenge free radicals as confirmed by electron paramagnetic resonance spectroscopy. Irradiation of graphene-containing polymer composites resulted in the largest increase in modulus and hardness compared to either irradiation or addition of graphene to PEB alone. This study provides new insight into the role of graphene in polymer matrices during irradiation and suggests that irradiated graphene-polymer composites could emerge as promising materials for use as articulating surfaces in biomedical implants.

Autoxidation of pyrogallol in alkaline medium is characterized by increases in oxygen consumption, absorbance at 440 nm, and absorbance at 600 nm. The primary products are H2O2 by reduction of O2 and pyrogallol-ortho-quinone by oxidation of pyrogallol. About 20 % of the consumed oxygen was used for ring opening leading to the bicyclic product, purpurogallin-quinone (PPQ). The absorbance peak at 440 nm representing the quinone end-products increased throughout at a constant rate. Prolonged incubation of pyrogallol in alkali yielded a product with ESR signal. In contrast the absorbance peak at 600 nm increased to a maximum and then declined after oxygen consumption ceased. This represents quinhydrone charge-transfer complexes as similar peak instantly appeared on mixing pyrogallol with benzoquinones, and these were ESR-silent. Superoxide dismutase inhibition of pyrogallol autoxidation spared the substrates, pyrogallol, and oxygen, indicating that an early step is the target. The SOD concentration-dependent extent of decrease in the autoxidation rate remained the same regardless of higher control rates at pyrogallol concentrations above 0.2 mM. This gave the clue that SOD is catalyzing a reaction that annuls the forward electron transfer step that produces superoxide and pyrogallol-semiquinone, both oxygen radicals. By dismutating these oxygen radicals, an action it is known for, SOD can reverse autoxidation, echoing the reported proposal of superoxide:semiquinone oxidoreductase activity for SOD. The following insights emerged out of these studies. The end-product of pyrogallol autoxidation is PPQ, and not purpurogallin. The quinone products instantly form quinhydrone complexes. These decompose into undefined humic acid-like complexes as late products after cessation of oxygen consumption. SOD catalyzes reversal of autoxidation manifesting as its inhibition. SOD saves catechols from autoxidation and extends their bioavailability.

The mixed alkali metal effect is a long-standing problem in glasses. Electron paramagnetic resonance (EPR) is used by several researchers to study the mixed alkali metal effect, but a detailed analysis of the nearest neighbor environment of the glass former using spin-Hamiltonian parameters was elusive. In this study we have prepared a series of vanadate glasses having general formula (mol %) 40 V2O5-30BaF2-(30 - x)LiF-xRbF with x = 5, 10, 15, 20, 25, and 30. Spin-Hamiltonian parameters of V(4+) ions were extracted by simulating and fitting to the experimental spectra using EasySpin. From the analysis of these parameters it is observed that the replacement of lithium ions by rubidium ions follows a "preferential substitution model". Using this proposed model, we were able to account for the observed variation in the ratio of the g parameter, which goes through a maximum. This reflects an asymmetric to symmetric changeover of the alkali metal ion environment around the vanadium site. Further, this model also accounts for the variation in oxidation state of vanadium ion, which was confirmed from the variation in signal intensity of EPR spectra.

Mn-doped SrTiO(3.0), when synthesized free of impurities, is a paramagnetic insulator with interesting dielectric properties. Since delocalized charge carriers are known to promote ferromagnetism in a large number of systems via diverse mechanisms, we have looked for the possibility of any intrinsic, spontaneous magnetization by simultaneous doping of Mn ions and electrons into SrTiO3 via oxygen vacancies, thereby forming SrTi(1-x)Mn(x)O(3-δ), to the extent of making the doped system metallic. We find an absence of any enhancement of the magnetization in the metallic sample when compared with a similarly prepared Mn doped, however, insulating sample. Our results, thus, are not in agreement with a recent observation of a weak ferromagnetism in metallic Mn doped SrTiO3 system.

We show from conventional magnetization measurements that the charge order (CO) is completely suppressed in 10 nm Pr(0.5)Ca(0.5)MnO(3)(PCMO 10) nanoparticles. Novel magnetization measurements, designed by a special high field measurement protocol, show that the dominant ground state magnetic phase is ferromagnetic-metallic (FM-M), which is an equilibrium phase, which coexists with the residual charge ordered anti-ferromagnetic phase (CO AFM) (an arrested phase) and exhibits the characteristic features of a 'magnetic glassy state' at low temperatures. It is observed that there is a drastic reduction in the field required to induce the AFM to FM transition (∼5-6 T) compared to their bulk counterpart (∼27 T); this phase transition is of first order in nature, broad, irreversible and the coexisting phases are tunable with the cooling field. Temperature-dependent magneto-transport data indicate the occurrence of a size-induced insulator-metal transition (T(M-I)) and anomalous resistive hysteresis (R-H) loops, pointing out the presence of a mixture of the FM-M phase and AFM-I phase.

Using electron spin resonance spectroscopy (ESR), we measure the rotational mobility of probe molecules highly diluted in deeply supercooled bulk water and negligibly constrained by the possible ice fraction. The mobility increases above the putative glass transition temperature of water, T(g) = 136 K, and smoothly connects to the thermodynamically stable region by traversing the so called "no man's land" (the range 150-235 K), where it is believed that the homogeneous nucleation of ice suppresses the liquid water. Two coexisting fractions of the probe molecules are evidenced. The 2 fractions exhibit different mobility and fragility; the slower one is thermally activated (low fragility) and is larger at low temperatures below a fragile-to-strong dynamic cross-over at approximately 225 K. The reorientation of the probe molecules decouples from the viscosity below approximately 225 K. The translational diffusion of water exhibits a corresponding decoupling at the same temperature [Chen S-H, et al. (2006) The violation of the Stokes-Einstein relation in supercooled water. Proc Natl Acad Sci USA 103:12974-12978]. The present findings are consistent with key issues concerning both the statics and the dynamics of supercooled water, namely the large structural fluctuations [Poole PH, Sciortino F, Essmann U, Stanley HE (1992) Phase behavior of metastable water. Nature 360:324-328] and the fragile-to-strong dynamic cross-over at approximately 228 K [Ito K, Moynihan CT, Angell CA (1999) Thermodynamic determination of fragility in liquids and a fragile-to-strong liquid transition in water. Nature 398:492-494].

Two new three-dimensional metal-organic frameworks (MOFs) [Mn(2)(mu(3)-OH)(H(2)O)(2)(BTC)] x 2 H(2)O, I, and [NaMn(BTC)], II (BTC = 1,2,4-benzenetricarboxylate = trimellitate) were synthesized and their structures determined by single-crystal X-ray diffraction (XRD). In I, the Mn(4) cluster, [Mn(4)(mu(3)-OH)(2)(H(2)O)(4)O(12)], is connected with eight trimellitate anions and each trimellitate anion connects to four different Mn(4) clusters, resulting in a fluorite-like structure. In II, the Mn(2)O(8) dimer is connected with two Na(+) ions through carboxylate oxygen to form mixed-metal distorted Kagome-related two-dimensional -M-O-M- layers, which are pillared by the trimellitate anions forming the three-dimensional structure. The extra-framework water molecules in I are reversibly adsorbed and are also corroborated by powder XRD studies. The formation of octameric water clusters involving free and coordinated water molecules appears to be new. Interesting magnetic behavior has been observed for both compounds. Electron spin resonance (ESR) studies indicate a broadening of the signal below the ordering temperature and appear to support the findings of the magnetic studies.

We report three prominent observations made on the nanoscale charge ordered (CO) manganites RE(1-x)AE(x)MnO(3) (RE = Nd,Pr; AE = Ca; x = 0.5) probed by temperature dependent magnetization and magneto-transport, coupled with electron magnetic/paramagnetic resonance spectroscopy (EMR/EPR). First, evidence is presented to show that the predominant ground state magnetic phase in nanoscale CO manganites is ferromagnetic and it coexists with a residual anti-ferromagnetic phase. Secondly, the shallow minimum in the temperature dependence of the EPR linewidth shows the presence of a charge ordered phase in nanoscale manganites which was shown to be absent from the DC static magnetization and transport measurements. Thirdly, the EPR linewidth, reflective of spin dynamics, increases significantly with a decrease of particle size in CO manganites. We discuss the interesting observations made on various samples of different particle sizes and give possible explanations. We have shown that EMR spectroscopy is a highly useful technique to probe the 'hindered charge ordered phase' in nanoscale CO manganites, which is not possible by static DC magnetization and transport measurements.

A new ac loss behaviour is observed in the superconducting state of Bi(2)Sr(2)CaCu(2)O(8) single crystals using a novel technique of measuring dissipation at radio frequencies. It is found that the ac loss in the superconducting state is larger than that in the normal state. This counter-intuitive result is explained in terms of the cumulative effect of repetitive decoupling of intrinsic Josephson junctions in the crystals and analysed in the framework of Ambegaokar-Baratoff theory. The ac losses are studied as a function of temperature, rf amplitude and magnetic field applied at different orientations. A peak in ac losses is observed in the superconducting state along the temperature scale. The amplitude of the peak decreases and shifts towards lower temperature with increasing field and also when the field orientation with respect to the c axis of the crystal changes from the perpendicular to parallel direction. The origin of the peak and its behaviour are discussed in the context of coupling energy of Josephson junctions present in the sample. In the presence of a magnetic field another peak in ac losses arises at temperatures close to T(c), which is associated with the Lorentz-force-driven motion of vortices.

The highly sensitive technique of spin-probe Electron Spin Resonance (ESR) has been used to study dynamics of carbon nanotubes. The ESR signals were recorded for the nitroxide free radical TEMPO in carbon nanotubes from 5 to 300 K. The onset of the fast dynamics of the probe molecule was indicated by appearance of a narrow triplet at 230 K. The ESR measurements were also done on TEMPO in methanol for the comparative studies in the same temperature range, and in the latter observations, no change in spectra was seen around 230 K. The results indicate the occurrence of a change in the dynamics of carbon nanotubes around this temperature.

Nanowires of Pr0.57Ca0.41Ba0.02MnO3 (PCBM) (diameter approximately 80-90 nm and length approximately 3.5 microm) were synthesized by a low reaction temperature hydrothermal method. Single-phase nature of the sample was confirmed by XRD experiments. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the morphology and microstructures of the nanowires. While the bulk PCBM is known to exhibit charge order (CO) below 230 K along with a ferromagnetic transition at 110 K, SQUID measurements on the nanowires of PCBM show that the charge order is completely absent and a ferromagnetic transition occurs at 115 K. However, the magnetization in the nanowires is observed to be less compared to that in the bulk. This observation of the complete 'melting' of the charge order in the PCBM nanowires is particularly significant in view of the observation of only a weakening of the CO in the nanowires of Pr0.5Ca0.5MnO3. Electron paramagnetic resonance experiments were also carried out on the PCBM nanowires using an X-band EPR spectrometer. Characteristic differences were observed in the line width of nanowires when compared with that of the bulk.

Nanoparticles (dia. approximately 5-7 nm) of Bi0.5X0.5(X = Ca, Sr)MnO3 are prepared by polymer assisted sol-gel method and characterized by various physico-chemical techniques. X-ray diffraction gives evidence for single phasic nature of the materials as well as their structures. Mono-dispersed to a large extent, isolated nanoparticles are seen in the transmission electron micrographs. High resolution electron microscopy shows the crystalline nature of the nanoparticles. Superconducting quantum interferometer based magnetic measurements from 10 K to 300 K show that these nanomanganites retain the charge ordering nature unlike Pr and Nd based nanomanganites. The CO in Bi based manganites is thus found to be very robust consistent with the observation that magnetic fields of the order of 130 T are necessary to melt the CO in these compounds. These results are supported by electron magnetic resonance measurements.

Three long-standing problems related to the physics of water, viz., the possibility of vitrifying bulk water by rapid quenching, its glass transition, and the supposed impossibility of obtaining supercooled water between 150 and 233 K, the so-called "no man's land" of its phase diagram, are studied using the highly sensitive technique of spin probe ESR. Our results suggest that water can indeed be vitrified by rapid quenching; it undergoes a glass transition at approximately 135 K, and the relaxation behavior studied using this method between 165 K and 233 K closely follows the predictions of the Adam-Gibbs model.

We analyze the equation used for simulating the lineshapes of broad electron paramagnetic resonance spectra in conducting samples (i.e., broad Dysonian lineshapes) where it becomes necessary to include the effects of both clockwise and counterclockwise rotating components of the microwave magnetic field. Using symmetry arguments, we propose a modification to the equation. We show that the modified equation fits the experimental results better than the equation used in literature.

Knowledge of the three-dimensional structures of HIV-1 protease and of its complexes with various inhibitors has played a key role in development of drugs against AIDS. Hexagonal crystals of unliganded tethered HIV-1 protease in which the enzyme conformation is identical to its ligand-bound state can be used in combination with the soaking method in order to identify potential inhibitor leads via X-ray diffraction. The advantages of the soaking method are the generality of application and the rapidity of structure determination for iterative structure-based drug design. Structures of two ligand complexes with HIV-1 protease determined using this method are shown to be very similar to the structures obtained earlier via co-crystallization.

We report the synthesis of fixed-size ZnS nanoclusters approximately 24 A in diameter with varying manganese concentrations. Various samples of Zn1-x MnxS, with x = 0, 0.02, 0.055, 0.09, and 0.13, have been prepared and characterized using X-ray diffraction, energy-dispersive analysis of X-rays, UV absorption, fluorescence emission and excitation, electron paramagnetic resonance (EPR), and magnetic susceptibility measurements. The manganese ions are found to substitute Zn randomly without giving rise to any clustering of Mn sites, as seen from EPR and magnetic susceptibility results. Our studies reveal that the band gap of the doped nanoclusters passes through a maximum as the manganese concentration is varied. Also, we observe orange emission from Mn2+ ions in the doped ZnS nanoclusters, apart from the blue emission characteristic of the ZnS defect states. The relative intensity of the orange emission compared with the blue varies with the manganese concentration in a nonmonotonic way. The inverse of susceptibility temperature plots can be plotted onto a universal curve by simple multiplicative constants, thus showing that the magnetic interactions between Mn2+ ions are weak.

Twelve t-butylperoxyamines (6-17) were synthesized as targeted antimalarials and evaluated for antimalarial activity in vivo against Plasmodium berghei in mice and in vitro against both chloroquine sensitive and chloroquine resistant strains of Plasmodium falciparum. Compound 8 was found to have highest potency with activity at 80 and 160mg/kg dose in vivo and compound 11 exhibited highest efficacy in vitro.

The semi-IPN hydrogel membranes of polyvinyl pyrrolidone (PVP) and beta-chitosan were synthesized by crosslinking beta-chitosan with glutaraldehyde. Hydrogel membranes were characterized by spectroscopic, swelling, thermal and mechanical properties. The in vitro biocompatibility of hydrogel membranes was studied by haemorheological method. These hydrogels have water contents in the range of 60-70% with a high fraction contributed by free water (> 45%). The gel composition, amount of cross-linking agent and swelling temperature plays an important role in swelling kinetics of these semi-IPN membranes. Melting temperature (Tm) of membranes increased with a decrease in endothermic peak with increasing beta-chitosan content. The tensile strength of membranes in the dry state was found to be high (29-43 MPa) and it increased with increasing beta-chitosan content. The in vitro haemorheological studies indicated the biocompatible nature of membranes with no significant changes in whole blood and plasma viscosity and red blood cell rigidity., (Copyright 2001 Kluwer Academic Publishers)

The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for antibiotic delivery. The hydrogels were synthesised by crosslinking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). The semi-IPN formation was confirmed by Fourier transform infrared spectroscopic (FTIR) analysis. Semi-IPNs, viz, air-dried and freeze-dried, were compared for their surface morphology, wettability, swelling properties and pH-dependent swelling. Air- and freeze-dried membranes were also incorporated with amoxicillin and antibiotic release was studied. Porous freeze-dried hydrogels (pore diameter, 39.20+/-2.66 microm) exhibited superior pH-dependent swelling properties over non-porous air-dried hydrogels. A high octane contact angle (144.20+/-0.580) of hydrogel was indicative of its hydrophilic nature. Increased swelling of hydrogels, under acidic conditions, was due to the protonation of a primary amino group on chitosan, as confirmed by FTIR analysis. Freeze-dried membranes released around 73% of the amoxicillin (33% by air-dried) in 3 h at pH 1.0 and, thus, had superior drug-release properties to air-dried hydrogels. Freeze-dried membranes could serve as potent candidates for antibiotic delivery in an acidic environment.

The neuromuscular blocking properties of an alkaloidal extract from the root of Inula royleana have been investigated in vitro using a combination of mechanical and electrophysiological approaches. Neurogenic twitches of the frog sartorius were profoundly inhibited by concentrations of the extract > or = 20 micrograms/ml, being reduced to 50% of control amplitude in approximately 90 s at a concentration of > or = 20 micrograms/ml. They were partially reversed by neostigmine (6 micrograms/ml), and by prolonged washout of the extract. Muscle surface action potentials, recorded with extracellular electrodes, also declined rapidly in amplitude in the presence of the extract. Direct muscle stimulation during inhibition by the extract elicited contractions and action potentials whose magnitudes were similar to control responses. Resting membrane potentials, and the intracellular input impedance of the skeletal muscle cells, were not significantly changed by the alkaloids. These results indicate that the extract has significant neuromuscular blocking activity of a partially or slowly reversible nature. The block appears to be exerted at the postjunctional end-plate nicotine receptors, thus offering promise for the identification of novel cholinergic receptor antagonist(s).

Several Baylis-Hillman adducts and their derivatives were synthesized and evaluated as targeted potential anti-malarials. The compounds 4, 7 and 9 were found to have highest potency against P. falciparum in vitro. The in vivo test result of compound 4 and 9 against P. berghei demonstrated activity at 80 mg/Kg dose level.

Synthetic analogues of a monoterpenic fragment of aplasmomycin were tested for their antimalarial activity in Plasmodium falciparum culture in vitro. The antimalarial activities of these agents were evaluated in chloroquine sensitive strains. Parasite growth was inhibited in a dose dependent manner in the presence of the synthetic compounds (3-9).

We investigated the hemorheological, hematological and biochemical parameters in 30 cases of acute lymphocytic leukemia (ALL), 21 cases of acute myelogenous leukemia (AML) and 30 cases of chronic myelogenous leukemia (CML). The parameters studied include whole blood viscosity, plasma viscosity, erythrocyte sedimentation rate (ESR), red cell filterability, hematocrit, platelet count and aggregation, fibrinogen, hemoglobin, leucocyte count, bleeding time and lactate dehydrogenase activity (LDH). In the cases of ALL we observed significant decrease in whole blood viscosity, hemoglobin, hematocrit and platelet count but an increase in plasma viscosity, fibrinogen, bleeding time and LDH activity. In the cases of AML, we observed increase in whole blood viscosity, plasma viscosity, ESR, fibrinogen, leucocyte count, bleeding time and LDH activity but decrease in the hemoglobin, hematocrit and platelet count. In the cases of CML, we observed an increase of whole blood viscosity, plasma viscosity, ESR, fibrinogen elevation but decreases in bleeding time. In all cases, red cell filterability was unaffected.

When discussing the rheological properties of normal and leukemic blood it must be considered that blood is a suspension of cells in aqueous solution which is also known as plasma. Whole blood viscosity and plasma viscosity were determined by Rheometer LS30 which allows measuring whole blood and plasma viscosity in the middle and low shear rate ranges. The measurements of the viscosity showed that whole blood and plasma behave as non-Newtonian power law fluid. The values of n (non-Newtonian index) and k (consistency index) of power law fluid were calculated for both leukemic blood and plasma samples. The importance of this phenomenon for the micro-circulation is discussed.

Seven analogues of monoterpenic fragment of aplasmomycin were synthesized as targeted antimalarial agents. The potency of the compound 6 was comparable with the sesquiterpene lactone artemisinin and the antibiotic aplasmomycin in vivo against Plasmodium berghei yoelli.

The effect of hydroxyurea on blood viscosity was studied in 10 patients with Philadelphia chromosome positive chronic myelogenous leukemia (CML) and hyperleukocytosis (white blood cell counts over 200 x 10(9)/l). All the patients had visible manifestations of leukostasis such as headache, blurred vision, retinal hemorrhage, pulmonary infiltrates, etc. Contraves LS 30 viscometer was used to measure the blood viscosity at 37 degrees C and at different shear rates on paired leukemic blood samples obtained before and after the hydroxyurea treatment. The blood viscosity was significantly higher in CML patients then normal subjects and decreased after treatment with hydroxyurea. In all the cases plasma viscosity was unaffected by the treatment.

Four naturally occurring analogues of forskolin were isolated. Forty-nine semisynthetic derivatives were prepared, incorporating structural alterations at the 1-, 6-, 7-, 9-, 11-, and 14/15-positions. Blood pressure lowering properties of 53 compounds were assessed in anesthetized normotensive cats and of 31 compounds in conscious spontaneously hypertensive (SH) rats. The positive inotropic properties of 25 compounds were investigated in an isolated guinea pig atrial preparation. Forskolin was unique among the compounds in its hypotensive activity in cats and in its positive inotropic properties. Although several derivatives displayed oral antihypertensive activity in the SH rats, none was significantly more potent than forskolin. The optimal structural requirements for activity are apparent, since they are found in forskolin itself.