Dielectric-waveguide mode of light propagation in p-n junctions

The condition for coherent laser emission from forward-biased p-n junctions [1-3] can be written as [4] [equation 1]... In order for the reported values [1-3] of Ic/A to agree with Eq. (1), must must use values pf d ~50 μ [4]. The question arises as to the nature of the mechanism which could confine the light generated near the junction to such small distances

In vitro comparison of antiviral drugs against feline herpesvirus 1

BACKGROUND: Feline herpesvirus 1 (FHV-1) is a common cause of respiratory and ocular disease in cats. Especially in young kittens that have not yet reached the age of vaccination, but already lost maternal immunity, severe disease may occur. Therefore, there is a need for an effective antiviral treatment. In the present study, the efficacy of six antiviral drugs, i.e. acyclovir, ganciclovir, cidofovir, foscarnet, adefovir and 9-(2-phosphonylmethoxyethyl)-2, 6-diaminopurine (PMEDAP), against FHV-1 was compared in Crandell-Rees feline kidney (CRFK) cells using reduction in plaque number and plaque size as parameters. RESULTS: The capacity to reduce the number of plaques was most pronounced for ganciclovir, PMEDAP and cidofovir. IC(50 (NUMBER) )values were 3.2 μg/ml (12.5 μM), 4.8 μg/ml (14.3 μM) and 6 μg/ml (21.5 μM), respectively. Adefovir and foscarnet were intermediately efficient with an IC(50 (NUMBER) )of 20 μg/ml (73.2 μM) and 27 μg/ml (140.6 μM), respectively. Acyclovir was least efficient (IC(50 (NUMBER) )of 56 μg/ml or 248.7 μM). All antiviral drugs were able to significantly reduce plaque size when compared with the untreated control. As observed for the reduction in plaque number, ganciclovir, PMEDAP and cidofovir were most potent in reducing plaque size. IC(50 (SIZE) )values were 0.4 μg/ml (1.7 μM), 0.9 μg/ml (2.7 μM) and 0.2 μg/ml (0.7 μM), respectively. Adefovir and foscarnet were intermediately potent, with an IC(50 (SIZE) )of 4 μg/ml (14.6 μM) and 7 μg/ml (36.4 μM), respectively. Acyclovir was least potent (IC(50 (SIZE) )of 15 μg/ml or 66.6 μM). The results demonstrate that the IC(50 (SIZE) )values were notably lower than the IC(50 (NUMBER) )values. The most remarkable effect was observed for cidofovir and ganciclovir. None of the products were toxic for CRFK cells at antiviral concentrations. CONCLUSION: In conclusion, measuring reduction in plaque number and plaque size are two valuable and complementary means of assessing the efficacy of an antiviral drug. By using these parameters for six selected antiviral drugs, we found that ganciclovir, PMEDAP, and cidofovir are the most potent inhibitors of FHV-1 replication in CRFK cells. Therefore, they may be valuable candidates for the treatment of FHV-1 infection in cats

Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors

<p>Abstract</p> <p>Background</p> <p>Activating mutations in Kit receptor tyrosine kinase or the related platelet-derived growth factor receptor (PDGFR) play an important role in the pathogenesis of gastrointestinal stromal tumors (GIST).</p> <p>Methods</p> <p>This study investigated the activity of motesanib, an inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3; PDGFR; and Kit, against primary activating Kit mutants and mutants associated with secondary resistance to imatinib. Single- and double-mutant isoforms of Kit were evaluated for their sensitivity to motesanib or imatinib in autophosphorylation assays and in Ba/F3 cell proliferation assays.</p> <p>Results</p> <p>Motesanib inhibited Kit autophosphorylation in CHO cell lines expressing primary activating mutations in exon 9 (AYins503-504, IC₅₀= 18 nM) and exon 11 (V560 D, IC₅₀= 5 nM; Δ552-559, IC₅₀= 1 nM). Motesanib also demonstrated activity against kinase domain mutations conferring imatinib resistance (V560D/V654A, IC₅₀= 77 nM; V560D/T670I, IC₅₀= 277 nM; Y823 D, IC₅₀= 64 nM) but failed to inhibit the imatinib-resistant D816V mutant (IC₅₀> 3000 nM). Motesanib suppressed the proliferation of Ba/F3 cells expressing Kit mutants with IC₅₀values in good agreement with those observed in the autophosphorylation assays.</p> <p>Conclusions</p> <p>In conclusion, our data suggest that motesanib possesses inhibitory activity against primary Kit mutations and some imatinib-resistant secondary mutations.</p

IL28B is associated with outcomes of chronic HBV infection

Purpose The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. Materials and Methods IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. Results Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p&#60;0.01; cirrhosis vs. controls, p&#60;0.01; HCC vs. controls, p&#60;0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p&#60;0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p&#60;0.001). Conclusion Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.</p

SYNERGISTIC CYTOTOXIC EFFECT OF STATINS AND BISPHOSPHONATES ON SQUAMOUS CELL CARCINOMA CELL LINE

Objective: The present study aimed at evaluating the in vitro cytotoxic effect of simvastatin (sv) and alendronate (aln) on squamous cell carcinoma cell line (Hep-2 cells).Methods: Hep-2 cells were divided into four groups; Control group where cells were cultured in the routine culture medium. Alendronate Group (A) consisting of cells cultured in aln in its IC 50. Simvastatin Group(S) cultured in sv in its IC 50. And finally, a combined group (A+S) comprising cells cultured in combined IC 50 dose of sv and aln. To assess the effect of these drugs on Hep-2 cells, cell viability was measured in addition to measuring vascular endothelial growth factor (VEGF) expression by Elisa.Results: In all groups, a decrease in the mean viability percentages of the treated Hep-2 cells in relation to control cells was observed in all groups. The combination of both agents exhibited a significant (P-values Ë‚0.05) synergistic effect on decreasing cell viability and angiogenesis of Hep-2 cells in vitro. VEGF measures in all groups were significantly lower than the control group (P-values Ë‚ 0.05). The combination of both drugs at their IC 50 doses can lower the VEGF production by Hep-2 cancer cells (P-values Ë‚ 0.05).Conclusion: A combination of sv and aln in their Ic50 doses has a dramatic effect on lowering the proliferation and VEGF expression in Hep-2 cancer cells cultured in vitro

Design, synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4-disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI$_{50}$ values ranging from 0.70 µM to 1.20 µM, compared to doxorubicin GI$_{50}$ value = 1.10 µM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC$_{50}$ values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC$_{50}$ = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC$_{50}$ values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC$_{50}$ = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking score

New Diaryl-1,2,4-triazolo[3,4- a ]pyrimidine Hybrids as Selective COX-2/sEH Dual Inhibitors with Potent Analgesic/Anti-inflammatory and Cardioprotective Properties

COX-2-selective drugs were withdrawn from the market just a few years after their development due to cardiovascular side effects. As a result, developing a selective COX-2 inhibitor as an anti-inflammatory agent with cardioprotective characteristics has become a prominent objective in medicinal chemistry. New 15 diaryl-1,2,4-triazolo[3,4-a]pyrimidine hybrids 8a–o were synthesized and investigated in vitro as dual COX-2/sEH inhibitors. Compounds 8b, 8m, and 8o have the highest potency and selectivity as COX-2 inhibitors (IC$_{50}$ = 15.20, 11.60, and 10.50 μM, respectively; selectivity index (COX-1/COX-2) = 13, 20, and 25, respectively), compared to celecoxib (COX-2; IC$_{50}$ = 42 μM; SI = 8). The 5-LOX inhibitory activity of compounds 8b, 8m, and 8o was further examined in vitro. Compounds 8m and 8o, the most effective COX-2 selective inhibitors, demonstrated stronger 5-LOX inhibitory action than the reference quercetin, with IC$_{50}$ values of 2.90 and 3.05 μM, respectively. Additionally, compounds 8b, 8m, and 8o were the most potent dual COX-2/sEH inhibitors, with IC$_{50}$ values against sEH of 3.20, 2.95, and 2.20 nM, respectively, and were equivalent to AUDA (IC$_{50}$ = 1.2 nM). In vivo investigations also demonstrated that these compounds were the most efficacious as analgesic/anti-inflammatory derivatives with a high cardioprotective profile against cardiac biomarkers and inflammatory cytokines. The docking data analysis inquiry helped better understand the binding mechanisms of the most active hybrids within the COX-2 active site and supported their COX-2 selectivity. Compounds 8b, 8m, and 8o exhibited a similar orientation to rofecoxib and celecoxib, with a larger proclivity to enter the selectivity side pocket than the reference compounds

Direct comparison of the histidine-rich protein-2 enzyme-linked immunosorbent assay (HRP-2 ELISA) and malaria SYBR green I fluorescence (MSF) drug sensitivity tests in Plasmodium falciparum reference clones and fresh ex vivo field isolates from Cambodia

BACKGROUND: Performance of the histidine-rich protein-2 enzyme-linked immunosorbent assay (HRP-2 ELISA) and malaria SYBR Green I fluorescence (MSF) drug sensitivity tests were directly compared using Plasmodium falciparum reference strains and fresh ex vivo isolates from Cambodia against a panel of standard anti-malarials. The objective was to determine which of these two common assays is more appropriate for studying drug susceptibility of “immediate ex vivo” (IEV) isolates, analysed without culture adaption, in a region of relatively low malaria transmission. METHODS: Using the HRP-2 and MSF methods, the 50% inhibitory concentration (IC(50)) values against a panel of malaria drugs were determined for P. falciparum reference clones (W2, D6, 3D7 and K1) and 41 IEV clinical isolates from an area of multidrug resistance in Cambodia. Comparison of the IC(50) values from the two methods was made using Wilcoxon matched pair tests and Pearson’s correlation. The lower limit of parasitaemia detection for both methods was determined for reference clones and IEV isolates. Since human white blood cell (WBC) DNA in clinical samples is known to reduce MSF assay sensitivity, SYBR Green I fluorescence linearity of P. falciparum samples spiked with WBCs was evaluated to assess the relative degree to which MSF sensitivity is reduced in clinical samples. RESULTS: IC(50) values correlated well between the HRP-2 and MSF methods when testing either P. falciparum reference clones or IEV isolates against 4-aminoquinolines (chloroquine, piperaquine and quinine) and the quinoline methanol mefloquine (Pearson r = 0.85-0.99 for reference clones and 0.56-0.84 for IEV isolates), whereas a weaker IC(50) value correlation between methods was noted when testing artemisinins against reference clones and lack of correlation when testing IEV isolates. The HRP-2 ELISA produced a higher overall success rate (90% for producing IC(50) best-fit sigmoidal curves), relative to only a 40% success rate for the MSF assay, when evaluating ex vivo Cambodian isolates. Reduced sensitivity of the MSF assay is likely due to an interference of WBCs in clinical samples. CONCLUSIONS: For clinical samples not depleted of WBCs, HRP-2 ELISA is superior to the MSF assay at evaluating fresh P. falciparum field isolates with low parasitaemia (<0.2%) generally observed in Southeast Asia

Mechanism of strength degradation for hot corrosion of alpha-SiC

Sintered alpha SiC was corroded by thin films of Na2SO4 and Na2CO3 molten salts at 1000%. This hot corrosion attack reduced room temperature strengths by as much as 50%. Strength degradation was porportional to the degree and uniformity of corrosion pitting attack as controlled by the chemistry of the molten salt. Extensive fractography identified corrosion pits as the most prevalent source of failure. A fracture mechanics treatment of the strength/pit depth relationship produced an average K sub IC equal to 2.6 MPa sub m 1/2, which is consistent with published values