Inhibition of Snake Venom Metalloproteinase by β-Lactoglobulin Peptide from Buffalo (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>) Colostrum

Bioactive peptide research has experienced considerable therapeutic interest owing to varied physiological functions, efficacy in excretion, and tolerability of peptides. Colostrum is a rich natural source of bioactive peptides with many properties elucidated such as anti-thrombotic, anti-hypertensive, opioid, immunomodulatory, etc. In this study, a variant peptide derived from β-lactoglobulin from buffalo colostrum was evaluated for the anti-ophidian property by targeting snake venom metalloproteinases. These are responsible for rapid local tissue damages that develop after snakebite such as edema, hemorrhage, myonecrosis, and extracellular matrix degradation. The peptide identified by LC-MS/MS effectively neutralized hemorrhagic activity of the Echis carinatus venom in a dose-dependent manner. Histological examinations revealed that the peptide mitigated basement membrane degradation and accumulation of inflammatory leucocytes at the venom-injected site. Inhibition of proteolytic activity was evidenced in both casein and gelatin zymograms. Also, inhibition of fibrinolytic and fibrinogenolytic activities was seen. The UV-visible spectral study implicated Zn²⁺ chelation, which was further confirmed by molecular docking and dynamic studies by assessing molecular interactions, thus implicating the probable mechanism for inhibition of venom-induced proteolytic and hemorrhagic activities. The present investigation establishes newer vista for the BLG-col peptide with anti-ophidian efficacy as a promising candidate for therapeutic interventions.     

PRISM: A video coding paradigm with motion estimation at the decoder.

We describe PRISM, a video coding paradigm based on the principles of lossy distributed compression (also called source coding with side information or Wyner-Ziv coding) from multiuser information theory. PRISM represents a major departure from conventional video coding architectures (e.g., the MPEGx, H.26x families) that are based on motion-compensated predictive coding, with the goal of addressing some of their architectural limitations. PRISM allows for two key architectural enhancements: (1) inbuilt robustness to "drift" between encoder and decoder and (2) the feasibility of a flexible distribution of computational complexity between encoder and decoder. Specifically, PRISM enables transfer of the computationally expensive video encoder motion-search module to the video decoder. Based on this capability, we consider an instance of PRISM corresponding to a near reversal in codec complexities with respect to today's codecs (leading to a novel light encoder and heavy decoder paradigm), in this paper. We present encouraging preliminary results on real-world video sequences, particularly in the realm of transmission losses, where PRISM exhibits the characteristic of rapid recovery, in contrast to contemporary codecs. This renders PRISM as an attractive candidate for wireless video applications.     

Evolution of glassy gratings with variable aspect ratios under surface diffusion

The structural evolution of surface gratings on a glassy material is investigated by means of molecular simulations. The gratings provide a means to probe surface diffusion in the vicinity of the glass transition temperature. A theory by Mullins [J. Appl. Phys. 30, 77 (1959)] is used to extract qu-antitative measures of surface diffusivity that rely on calculation of grating amplitude as a function of time. The simulations are implemented in the context of a model binary glass mixture [S. S. Ashwin and S. Sastry, J. Phys.: Condens. Matter 15, S1253 (2003)]. We find that surface diffusion is faster than bulk diffusion by several orders of magnitude, consistent with recent experimental data for an organic glass former. The diffusivities extracted by the grating-decay approach are consistent with those estimated on the basis of mean-squared particle displacements. The grating-decay approach, however, is more efficient than traditional techniques based on Einstein's diffusion equation. Grating decay is also more versatile and is shown to be applicable in a variety of sample geometries.     

Making unilamellar liposomes using focused ultrasound

Several techniques are available for making large unilamellar vesicles (LUV) with an average diameter of approximately 100 nm, widely employed as model biomembranes as well as vehicles for drug delivery. Here we describe the use of adaptive focused ultrasound (AFU) for the preparation of LUV from multilamellar vesicles (MLV) and studied the effects of ultrasound intensity and number of cycles per burst (CPB) on the average size of vesicles produced. CPB determines the duration of the intermittent pressure wavetrains emitted by the transducer, and the corresponding relaxation periods. Preliminary experiments indicated that CPB controls the size of vesicles assembling after the disruption of MLV by ultrasound and optimum values for obtaining LUV could be iterated. The sizes and lamellarity of LUV were assessed by dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), and fluorescence quenching. AFU provides a simple and easy to use approach for making liposomes with several advantages: it is minimally invasive and involves no loss of material. Precisely controlled wavelengths are employed with a significant reduction in the presence of hot spots, which could destroy some biological materials of interest.     

A chimeric antibody to L1 cell adhesion molecule shows therapeutic effect in an intrahepatic cholangiocarcinoma model

Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the intrahepatic bile duct epithelium, has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Thus, there is an urgent need to develop new effective therapeutic strategies for this disease. We previously found that L1 cell adhesion molecule (L1CAM) plays an important role in tumor progression of ICC, and we generated a murine mAb, A10-A3 (IgG1), that binds to the Ig1 domain of L1CAM. In the present study, we further characterized A10-A3, constructed a chimeric A10-A3 antibody (cA10-A3) containing the constant regions of human IgG1, and evaluated the therapeutic potential in a human ICC xenograft nude mice model. The affinities (KD) of A10-A3 and cA10-A3 for soluble L1CAM were 1.8 nM and 1.9 nM, respectively, as determined by competition ELISA. A10-A3 inhibited L1CAM homophilic binding and was slowly internalized into the tumor cells, but it did not significantly inhibit proliferation of ICC cells in vitro. cA10-A3 mediated antibody- dependent cell-mediated cytotoxicity in vitro and displayed anti-tumor activity in the ICC animal model. These results suggest that the humanized A10-A3 antibody may have potential as an anticancer agent for the treatment of ICC.     

Synthesis,characterization and hydrogen sorption studies of mixed sodium‐potassium alanate

The aim of the present investigation is to synthesize mixed sodium potassium alanate (K₂NaAlH₆) and to explore its hydrogen sorption characteristics. K₂NaAlH₆ is synthesized through ball milling of KH and NaAlH₄ in the molar ratio 2:1 under hydrogen pressure of 10 bar. The temperature programmed desorption experiment shows that the synthesized K₂NaAlH₆ has peak desorption temperature of ∼352°C and reveals appreciable rehydrogenation kinetics under 6 bar hydrogen pressure at 300°C. The investigations are also focused on the catalytic effect of carbon nanostructures (CNS) namely, the graphene sheet (GS) and single wall carbon nanotube (SWCNT) and titanium halides (TiCl₃ and TiF₃) on K₂NaAlH₆. In the case of graphene and SWCNT catalyzed K₂NaAlH₆, the peak desorption temperature gets reduced to ∼347°C and ∼341°C respectively. The catalytic effects of CNS and titanium halide on K₂NaAlH₆ are also compared in the investigation. Between the two types of catalysts, halides are found to be better than CNS and out of the two halides, TiF₃ is found to be the best catalyst for hydrogen sorption in K₂NaAlH₆. The peak desorption temperature decreases significantly from 352°C to ∼324°C for TiF₃ catalyzed K₂NaAlH₆. Thus, the desorption activation energy reduces drastically from 124.43 kJ/mol (synthesized K₂NaAlH₆) to 88.05 kJ/mol for TiF₃ catalyzed K₂NaAlH₆.     

Analysis of 226Ra, 232Th and 40K in soil samples for the assessment of the average effective dose

The activity concentrations of the natural radionuclides namely ²³⁸Ra, ²³²Th and ⁴⁰K are measured for soil samples collected from different locations of Faridkot and Mansa districts of Punjab. HPGe detector, based on high-resolution gamma spectrometry system is used for the measurement of activity concentration. The range of activity concentrations of ²²⁶Ra, ²³²Th and ⁴⁰K in the soil from the studied areas varies from 21.42 Bq kg⁻¹ to 40.23 Bq kg⁻¹, 61.01 Bq kg⁻¹ to 142.34 Bq kg⁻¹ and 227.11 Bq kg⁻¹ to 357.13 Bq kg⁻¹ with overall mean values of 27.17 Bq kg⁻¹, 95.22 Bq kg⁻¹ and 312.76 Bq kg⁻¹, respectively. Radium equivalent activities are calculated for the analyzed samples to assess the radiation hazards arising due to the use of these soil samples in the construction of dwellings. The absorbed dose rate calculated from activity concentration of ²²⁶Ra, ²³²Th and ⁴⁰K ranges between 9.87 and 18.55, 38.01 and 88.68 and 9.40 and 14.79 nGy h⁻¹, respectively. The total absorbed dose in the study area ranges from 61.10 nGy h⁻¹ to 112.86 nGy h⁻¹ with an average value of 84.80 nGy h⁻¹. The calculated values of external hazard index (H _ex) for the soil samples of the study area range from 0.36 to 0.68. Since these values are lower than unity, according to the Radiation Protection 112 (European Commission, 1999) report, soil from these regions is safe and can be used as construction material without posing any significant radiological threat to population. The corresponding average annual effective dose for indoor and outdoor measured in the study area are 0.42 mSv and 0.10 mSv respectively.      

Cerebral blood flow estimation from perfusion-weighted MRI using FT-based MMSE filtering method

INTRODUCTION: Perfusion-weighted MRI can be used for estimating blood flow parameters using bolus tracking technique based on dynamic susceptibility contrast MRI. In order to extract flow parameters, several deconvolution techniques have been proposed, of which the singular value decomposition (SVD) and Fourier transform (FT)-based techniques are more popular and widely used. In this work, an FT-based method has been proposed that involves derivation of an optimal shaped filter (defined as a filter function) estimated using minimum mean-squared error (MMSE) technique in the frequency domain. The proposed technique has been compared with the well-established SVD technique using simulation experiments. SIMULATION METHODS: Simulation was performed in multiple steps. An arterial input function (AIF) was first defined based on a certain blood flow value. The T2* signal change was then derived from this AIF, and noise was added to the signal. Then, a unique and optimal shaped filter function Phi(f) was derived in order to obtain the best estimate of scaled residue function. One way is by minimizing the mean-squared error between the noiseless and noisy scaled residue function, i.e., using an MMSE method. The effect of low and moderate noise and distorted AIF on cerebral blood flow (CBF) estimates was obtained by using FT-based MMSE method. Results were compared with the SVD technique. In this work, SVD technique was assumed to be the standard reference deconvolution technique. RESULTS AND DISCUSSION: For low-noise condition, the FT-based technique was more stable than the SVD technique, while for moderate noise, both techniques consistently underestimated CBF. SVD technique was found to be more stable in presence of AIF distortions. However, SVD technique was found to be unstable due to AIF delay compared to the FT-based MMSE method. The shaped filter function was found to be sensitive to effect of AIF distortions.