Cancer/testis antigens as molecular drug targets using network pharmacology.

Present chemotherapeutic drugs have limited efficacy and severe side effects. Considering the complexity of cancer, an effective strategy is necessary to discover multiple new drug targets. Cancer/testis antigens are vital for cancer cell progression. We have performed a computational network analysis of cancer/testis antigens and assessed these antigens as drug targets. During this analysis, protein interaction network of 700 human CT antigens was investigated. CT antigen network consisted of eight independent components. Four major hubs and two minor hubs were identified that play nodal role in the flow of information across the largest network. We have predicted 30 potential drug targets by analysing several topological parameters such as betweenness centrality, cluster coefficient and probable protein complexes. Structural and functional roles of potential drug targets have also been anatomized. Analysis of the CT antigen network enables us to pinpoint a set of candidate proteins that if targeted could be detrimental for cancerous cell without affecting any normal cell. The list of putative proteins is a starting point for experimental validation and may help further in the discovery of new anticancer drug targets.

Dynamics of ultrafine particles inside a roadway tunnel.

Size-segregated ultrafine particles from motor vehicles were investigated in the Craeybeckx tunnel (E19 motorway, Antwerp, Belgium) at two measurement sites, at 100 and 300 m inside the tunnel, respectively, during March 2008. It was observed that out of the three size modes, nucleation, Aitken, and accumulation, Aitken mode was the most dominant size fraction inside the tunnel. The diurnal variation in ultrafine particle (UFP) levels closely follows the vehicular traffic inside the tunnel, which was maximum during office rush hours, both in the morning and evening and minimum during night-time around 3 am. The tunnel data showed very high growth rates in comparison with free atmosphere. The average condensation sink during the growth period was 14.1-17.3 × 10(-2) s(-1). The average growth rate (GR) of geometric mean diameter was found to be 18.6 ± 2.45 nm h(-1). It was observed that increase in Aitken mode was related to the numbers of heavy-duty vehicles (HDV), as they emit mainly in the Aitken mode. The higher Aitken mode during traffic jams correlated well with HDV numbers. At the end of the tunnel, sudden dilution leading to fast coagulation was responsible for the sudden drop in the UFP number concentration.

Fatigue Life Assessment of 65Si7 Leaf Springs: A Comparative Study.

The experimental fatigue life prediction of leaf springs is a time consuming process. The engineers working in the field of leaf springs always face a challenge to formulate alternate methods of fatigue life assessment. The work presented in this paper provides alternate methods for fatigue life assessment of leaf springs. A 65Si7 light commercial vehicle leaf spring is chosen for this study. The experimental fatigue life and load rate are determined on a full scale leaf spring testing machine. Four alternate methods of fatigue life assessment have been depicted. Firstly by SAE spring design manual approach the fatigue test stroke is established and by the intersection of maximum and initial stress the fatigue life is predicted. The second method constitutes a graphical method based on modified Goodman's criteria. In the third method codes are written in FORTRAN for fatigue life assessment based on analytical technique. The fourth method consists of computer aided engineering tools. The CAD model of the leaf spring has been prepared in solid works and analyzed using ANSYS. Using CAE tools, ideal type of contact and meshing elements have been proposed. The method which provides fatigue life closer to experimental value and consumes less time is suggested.

Effect of Assembly Stresses on Fatigue Life of Symmetrical 65Si7 Leaf Springs.

The maximum stress induced plays vital role in fatigue life improvement of leaf springs. To reduce this maximum stress, leaves with different unassembled cambers are assembled by pulling against each other and a common curvature is established. This causes stress concentration or sets assembly stress in the assembled leaf springs which is subtractive from load stress in master leaf while it is additive to load stress for short leaves. By suitable combination of assembly stresses and stepping, it is possible to distribute the stress and improve the fatigue life of the leaf spring. The effect of assembly stresses on fatigue life of the leaf spring of a light commercial vehicle (LCV) has been studied. A proper combination of stepping and camber has been proposed by taking the design parameters into consideration, so that the stress in the leaves does not exceed maximum design stress. The theoretical fatigue life of the leaf springs with and without considering the assembly stresses is determined and compared with experimental life. The numbers of specimens are manufactured with proposed parameters and tested for load rate, fatigue life on a full scale leaf springs testing machine. The effect of stress range, maximum stress, and initial stress is also discussed.

A-90 Day Gavage Safety Assessment of Boswellia serrata in Rats.

The present study deals with the evaluation and assessment of the safety/toxic potential of Boswellia serrata, a well known Ayurvedic herb used to treat disorders of digestive system, respiratory ailments and bone related diseases. A repeated dose oral (90 days) toxicity study of Boswellia serrata was carried out. For this, 10 rats of each sex were treated with the Boswellia serrata at three different doses i.e. 100, 500 and 1000 mg/kg B. wt. /day. As a control, 10 rats of each sex were treated with corn oil only which was the vehicle. Two groups consisting of five male and five female rats were kept as control recovery and high dose recovery group which were treated with the vehicle (corn oil) and the Boswellia serrata at the dose of 1000 mg/kg B. wt. Animals of control recovery and high dose recovery groups were further observed for 28 days without any treatment. From this study, it was found that the rats treated with high dose of the Boswellia serrata gained their body weight with much less rate than that of the control group. However, during the recovery period, the loss in body weight gain as observed during the study period exhibits a reversible effect on the metabolic activity and recovered. The results also indicate that Boswellia serrata is relatively safe in rat up to the dose of 500 mg/kg B.wt. as no adverse impact on health factors was observed. Thus, the No observed adverse effect level is 500 mg/kg B. wt.

Renal vein thrombosis in nephrotic syndrome--a prospective study and review.

The incidence of renal vein thrombosis (RVT) and other thrombo-embolic phenomena was evaluated in 44 unselected patients with nephrotic syndrome. Renal vein thrombosis was demonstrated by selective renal venography in 10 patients and at post-mortem in one. Extension of the thrombus from the renal veins into the inferior vena cava was seen in 3 patients. Evidence of thrombo-embolism elsewhere in the body was seen in the form of thrombophlebitis in the lower extremities in 4 patients (9.1%), pulmonary embolism in 3 (6.8%) and myocardial infarction in one (2.3%). Of the 11 patients with RVT, renal histology showed membranous glomerulonephritis in 3, minimal change nephritis in 5, membrano-proliferative in one and focal and diffuse proliferative glomerulonephritis in one patient each. The characteristics clinical findings such as gross haematuria and flank pain were noted in only 3 patients with RVT. No significant difference could be detected between the plasma fibrinogen, serum cholesterol, beta-lipoprotein, triglycerides and phospholipid concentration of those who showed RVT and the remainder in whom RVT was not demonstrated. The possible mechanisms involved in the pathogenesis of RVT in nephrotic syndrome are discussed.