Design of water-soluble, thiol-reactive polymers of controlled molecular weight: a novel multivalent scaffold

Multivalent molecules, i.e.?scaffolds presenting multiple copies of a suitable ligand, constitute an emerging class of nanoscale therapeutics. We present a novel approach for the design of multivalent ligands, which allows the biofunctionalization of polymers with proteins or peptides in a controlled orientation. It consists of the synthesis of water-soluble, activated polymer scaffolds of controlled molecular weight, which can be biofunctionalized with various thiolated ligands in aqueous media under mild conditions. These polymers were synthesized by ring-opening metathesis polymerization (ROMP) and further modified to make them water-soluble. The incorporation of chloride groups activated the polymers to react with thiol-containing peptides or proteins, and the formation of multivalent ligands in aqueous media was demonstrated. This strategy represents a convenient route for synthesizing multivalent ligands of controlled dimensions and valency.     

Ultra-Thin High-K Dielectric Profile Based NBTI Compact Model for Nanoscale Bulk MOSFET

Silicon - Negative Bias Temperature Instability (NBTI) is a key reliability and consistency issue for ultra-scaled Silicon IC technology with substantial consequences on both analog and digital...     

Structural,optical, cytotoxicity,and antimicrobial properties of MgO,ZnO and MgO/ZnO nanocomposite for biomedical applications

In this study, MgO nanoparticles were successfully fabricated and incubated inside ZnO NPs to form MgO/ZnO nanocomposite for biomedical applications. The x-ray diffraction analysis of MgO, ZnO, and MgO/ZnO has shown the single-phase x-ray diffraction patterns through X'pert High score. The crystallite sizes were calculated as 18 nm, 42 nm, and 53 nm, respectively. The average particle size of MgO, ZnO, and MgO/ZnO nanopowders depicted from secondary electron images of field emission electron microscopy were 56 nm, 400 nm, and 450 nm, respectively. The presence of MgO NPs inside ZnO NPs was confirmed by transmission electron microscopy. The elemental dispersive spectroscopy of MgO, given the peaks of oxygen and magnesium, also showed only zinc and oxygen peaks in ZnO, which confirms no other impurities in MgO and ZnO powders. The elemental analysis of MgO/ZnO nanocomposite showed the peaks of Zinc and Oxygen, along with a tiny peak of Mg. The photoluminescence and UV–vis spectroscopy revealed the absorbance fluorescence limit of the nanomaterials. Fourier transform infrared spectroscopy confirmed the several groups present in the nanocomposite. The biocompatibility of MgO, ZnO, and MgO/ZnO was observed with human peripheral blood mononuclear cells. The cytotoxicity studies were also performed against human cancer (liver and breast) cell lines. The MgO, ZnO, and MgO/ZnO exhibited the antimicrobial properties against Escherichia coli and Staphylococcus aureus.     

Targets (Metabolic Mediators) of Therapeutic Importance in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC), an extremely aggressive invasive cancer, is the fourth most common cause of cancer-related death in the United States. The higher mortality in PDAC is often attributed to the inability to detect it until it has reached advanced stages. The major challenge in tackling PDAC is due to its elusive pathology, minimal effectiveness, and resistance to existing therapeutics. The aggressiveness of PDAC is due to the capacity of tumor cells to alter their metabolism, utilize the diverse available fuel sources to adapt and grow in a hypoxic and harsh environment. Therapeutic resistance is due to the presence of thick stroma with poor angiogenesis, thus making drug delivery to tumor cells difficult. Investigating the metabolic mediators and enzymes involved in metabolic reprogramming may lead to the identification of novel therapeutic targets. The metabolic mediators of glucose, glutamine, lipids, nucleotides, amino acids and mitochondrial metabolism have emerged as novel therapeutic targets. Additionally, the role of autophagy, macropinocytosis, lysosomal transport, recycling, amino acid transport, lipid transport, and the role of reactive oxygen species has also been discussed. The role of various pro-inflammatory cytokines and immune cells in the pathogenesis of PDAC and the metabolites involved in the signaling pathways as therapeutic targets have been previously discussed. This review focuses on the therapeutic potential of metabolic mediators in PDAC along with stemness due to metabolic alterations and their therapeutic importance.     

Mean-stress and oxidation effects on fatigue behaviour of CM 247 DS LC alloy

During present investigations, an attempt was made to understand the effect of mean stress and oxidation on low cycle fatigue (LCF) behaviour of CM 247 DS LC alloy at T?=?850°C. A significant reduction in fatigue life was observed during LCF tests conducted at strain ratio (R) of 0 as compared to R?=??1. Reduction in fatigue life is attributed to the synergistic effect of mean stress, oxidation and the expanding precipitates within the grain boundaries which imparts high stresses at the grain boundary leading to the intergranular cracking. Additionally, to account the effect of mean stress on fatigue life of the alloy CM 247 DS LC empirical relations developed by Smith–Watson–Topper (SWT) and Morrow were used.     

Simulation model for electron irradiated IGZO thin film transistors

An efficient drain current simulation model for the electron irradiation effect on the electrical parameters of amorphous In-Ga-Zn-O (IGZO) thin-film transistors is developed.The model is developed based on the specifications such as gate capacitance,channel length,channel width,flat band voltage etc.Electrical parameters of un-irradiated IGZO samples were simulated and compared with the experimental parameters and 1 kGy electron irradiated parameters.The effect of electron irradiation on the IGZO sample was analysed by developing a mathematical model.     

Metabolism and pharmacokinetics of 1-(2''-trimethylacetoxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP117) in the rat

A modified endoscopic technique for anterior cruciate ligament (ACL) reconstruction using an autologous patellar tendon graft is described using the early results for 120 patients. A special technique using an oscillating hollow saw allows for the rapid and standardized harvest of cylindrical bone plugs, ensuring safe and adequate femoral press-fit fixation. The complications encountered included one fracture of a bone back on plugging in as well as two cases with revision procedures for interference screw fixation due to insufficient femoral anchorage. Within the framework of a prospective study, all 120 patients underwent a control arthroscopy after the first postoperative year showing viable and mechanically stable grafts in 64 (53.3%) of the patients. In 44 patients (36.7%), viable though somewhat lax grafts were found, whereas the remaining 12 patients (10%) only showed insufficient tissue residues. All of these cases were the result of a ventral misplacement of the femoral insertion site representing the primary complication of transtibial technique. The results of the control arthroscopies showed a highly significant correlation with the clinical results for the IKDC score obtained in a follow-up after an average 29 (18 to 36) months. The results for stability according to the IKDC rating scale showed a normal or near-normal knee function in 76.7%. With regard to the subjective results in the IKDC rating scale, 83.3% of the patients (n = 100) assessed their knee function as normal or almost normal. The location and positioning of the femoral and tibial tunnel were evaluated in an exact radiographic evaluation showing an "ideal position" of the graft in only 94 cases (78.3%). Statistically, a significant correlation of stability with the femoral fixation site could be shown.