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Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole.

Working electrode (WE) fabrication offers significant challenges in terms of achieving high-efficiency dye-sensitized solar cells (DSCs). We have combined the beneficial effects of vertical nanorods grown on conducting glass substrate for charge transport and mesoporous particles for dye loading and have achieved a high photoconversion efficiency of (η) > 11% with an internal quantum efficiency of ∼93% in electrode films of thickness ∼7 ± 0.5 μm. Controlling the interface between the vertical nanorods and the mesoporous film is a crucial step in attaining high η. We identify three parameters, viz., large surface area of nanoparticles, increased light scattering of the nanorod-nanoparticle layer, and superior charge transport of nanorods, that simultaneously contribute to the improved photovoltaic performance of the WE developed.

The title compound, C16H14N2O3, has an E conformation about the azo-benzene [-N=N- = 1.2481 (16) Å] linkage. The benzene rings are almost coplanar [dihedral angle = 1.36 (7)°]. The O atoms of the carb-oxy-lic acid group are disordered over two sets of sites and were refined with an occupancy ratio of 0.5:0.5. The two disordered components of the carb-oxy-lic acid group make dihedral angles of 1.5 (14) and 3.8 (12)° with the benzene ring to which they are attached. In the crystal, mol-ecules are linked via pairs of O-H⋯O hydrogen bonds, forming inversion dimers. The dimers are connected via C-H⋯O hydrogen bonds, forming ribbons lying parallel to [120]. These ribbons are linked via C-H⋯π inter-actions, forming slabs parallel to (001).

A detailed study on the surface properties of oleic acid-stabilized PtNi nanoparticles supported on silica is reported. The oleic acid-stabilized PtNi nanoparticles were synthesized using NaBH4 as the reducing agent at various temperatures and oleic acid concentrations, prior to incorporation onto the silica support. X-ray diffraction studies of the unsupported oleic acid-stabilized PtNi particles revealed that the PtNi existed as alloys. Upon incorporation onto silica support, surface properties of the catalysts were investigated using H2-temperature reduction (H2-TPR), H2-temperature desorption (H2-TPD) and H2-chemisorption techniques. It was found that for the bimetallic catalysts, no oxides or very little oxidation occurred. Furthermore, these catalysts exhibited both Pt and Ni active sites on its surface though the availability of Ni active sites was dominant. A comparison of the surface properties of these materials with those prepared without oleic acid in our previous work [N. H. H. Abu Bakar et al., J. Catal. 265, 63 (2009)] and how they affect the hydrogenation of benzene is also discussed.

Macrobenthos in coastal environment that play a significant role in the food web. It could also use as a good indicator of aquatic ecosystem health. The abundance and composition of macrobenthos in Bakkhali channel system, Cox's Bazar were conducted in relation to the soil parameters. Samples were collected using Ekman Berge bottom grab from five different stations of Bakkhali channel. Macrobenthos were comprised of five major groups namely Polychaeta (9.96-30.31%), Oligochaeta (3.68-59.707%), Crustacea (0.02-58.40%), Bivalvia (1.40-82.09%) and Gastropoda (0.08-4.25%). Total number of macrobenthos was higher at station I (9000 individuals m(-2)) and station II (8517 individuals m(-2)) compared to other stations. Shannon diversity index among the stations ranged from 0.65-1.04. Soil pH and soil moisture ranged from 6.1-6.4 and 23.44-31.29%, respectively. The highest organic carbon concentration was observed at station I (2.11%) and lowest at station III (1.40%). Maximum fraction of sand by weight was found at stations II (81.88%) and III (87.88) while the highest fraction of clay (21.52%) and silt (8.0%) were recorded in station I. It was observed that benthic bivalves were positively correlated (r = 0.891, p > 0.05) with silt fraction of the sediments.

One of the major concerns in global public health and the dairy industry is the emergence of host-specific virulent Staphylococcus aureus strains. The high degree of stability of the species genome renders detection of genetic microvariations difficult. Thus, approaches for the rapid tracking of specialized lineages are urgently needed. We used clumping factor A (clfA) to profile 87 bovine mastitis isolates from four regions in Canada and compared the results to those obtained by pulsed-field gel electrophoresis (PFGE) and spa typing. Twenty-five pulsotypes were obtained by PFGE with an index of discrimination of 0.91. These were assigned to six PFGE lineage groups A to F and seven spa types, including two novel ones. Group A had 48.3% of the isolates and group D had 43.7% of the isolates, while only 8% of the isolates were variable. The results of antimicrobial susceptibility testing indicated that all isolates were sensitive to methicillin and the non-beta-lactam antibiotics, while three isolates were resistant to penicillin and one isolate was resistant to tetracycline. All isolates had the clfA gene and belonged to 20 clfA repeat types with an index of discrimination of 0.90. The dominant clfA types, types X, Q, C, and Z, formed 82% and 43% of PFGE groups A and D, respectively, and had copy numbers that varied only within a narrow range of between 46 and 52 copies, implying clonal selection. The rest were variable and region specific. Furthermore, the dominant groups contained subpopulations in different regions across Canada. Sequence information confirmed the relatedness obtained by the use of clfA repeat copy numbers and other methods and further revealed the occurrence of full-repeat deletions and conserved host-specific codon-triplet position biases at 18-bp units. Thus, concordant with the results of PFGE and spa typing, clfA typing proved useful for revealing the clonal nature of the mastitis isolate lineage and for the rapid profiling of subpopulations with comparable discriminatory powers.

Grafting of free maleimide and epoxide pendant groups onto the surface of approximately 7-nm silica nanoparticles was investigated. Glycidyloxypropyl groups (3-glycidyloxypropyltrimethoxysilane and 3-aminopropyltrimethoxysilane) that carried epoxide groups and aminopropyl groups were grafted to the silica surface with the help of condensation reactions. Maleimide groups [1,1(')-(methylenedi-4,1-phenelene) bismaleimide] were introduced to the silica surface via nucleophilic addition reaction with the aminopropyl groups pre-grafted onto the surface. The grafted silica samples were characterized using CHN, FTIR, DSC, TGA-FTIR, and 13C and 29Si CP/MAS NMR spectroscopy. NMR analyses revealed that all the functional groups were covalently bonded to the silica surface and most of the maleimide and epoxide rings remained intact on surface. DSC analysis showed that the epoxide groups were more reactive than the maleimide groups.

Objective: To determine the risk factors for premature myocardial infarction among young South Asians., Design and Setting: Case-control study in a hospital admitting unselected patients with non-fatal acute myocardial infarction., Methods and Subjects: Risk factor assessment was done in 193 subjects aged 15-45 years with a first acute myocardial infarct, and in 193 age, sex, and neighbourhood matched population based controls., Results: The mean (SD) age of the subjects was 39 (4.9) years and 326 (84.5%) were male. Current smoking (odds ratio (OR) 3.82, 95% confidence interval (CI) 1.47 to 9.94), use of ghee (hydrogenated vegetable oil) in cooking (OR 3.91, 95% CI 1.52 to 10.03), raised fasting blood glucose (OR 3.32, 95% CI 1.21 to 8.62), raised serum cholesterol (OR 1.67, 95% CI 1.14 to 2.45 for each 1.0 mmol/l increase), low income (OR 5.05, 95% CI 1.71 to 14.96), paternal history of cardiovascular disease (OR 4.84, 95% CI 1.42 to 16.53), and parental consanguinity (OR 3.80, 95% CI 1.13 to 1.75) were all independent risk factors for acute myocardial infarction in young adults. Formal education versus no education had an independently protective effect on acute myocardial infarction (OR 0.04, 95% CI 0.01 to 0.35)., Conclusions: Tobacco use, ghee intake, raised fasting glucose, high cholesterol, paternal history of cardiovascular disease, low income, and low level of education are associated with premature acute myocardial infarction in South Asians. The association of parental consanguinity with acute myocardial infarction is reported for the first time and deserves further study.

The ability to predictably achieve long-term osseointegration in patients with compromised anatomical resources has been demonstrated numerous times in modern oral implantology. Recently, clinical attention has focused on new methods of reducing treatment time. One-stage surgical procedures and immediate loading of implants at the time of placement are two techniques that have demonstrated promising clinical results. A prospective clinical study of immediately splinting and loading a new, one-stage implant is currently in progress in the United States and France. An overview of the implant design and presentation of one case study from the University of Pittsburgh demonstrates how this promising technique is performed.

A panel of 24 methicillin-resistant Staphylococcus aureus strains was distributed to 15 laboratories in Canada to evaluate their in-house pulsed-field gel electrophoresis (PFGE) protocols and interpretation criteria. Attempts to compare fingerprint images using computer-aided analysis were not successful due to variability in individual laboratory PFGE protocols. In addition, individual site interpretation of the fingerprint patterns was inadequate, as 7 of 13 sites (54%) made at least one error in interpreting the fingerprints from the panel. A 2-day standardized PFGE protocol (culture to gel image) was developed and distributed to all of the sites. Each site was requested to use the standardized protocol on five strains from the original panel. Thirteen sites submitted gel images for comparisons. The protocol demonstrated excellent reproducibility and allowed interlaboratory comparisons with Molecular Analyst DST software (Bio-Rad) and 1.5% band tolerance.

Myocardial function is impaired 24 h after the induction of sepsis, however, recovery of left ventricular (LV) function after 35 min of global ischemia is complete. The mechanisms by which this protection occurs are unknown. Ischemic preconditioning, another form of myocardial protection from ischemia/reperfusion (I/R) injury, has been shown to be modulated by ATP-sensitive potassium (K+ATP) channels. To investigate the role of K+ATP channels in the regulation of coronary flow (CF) and protection from I/R injury in septic rat hearts, we assessed the effects of the K+ATP channel antagonist glibenclamide (GLIB) and the agonist cromakalim (CROM) on pre- and post-ischemic CF and left ventricular developed pressure (LVDP). Although GLIB decreased pre-ischemic CF in both control and septic rat hearts, LVDP was unaffected. After I/R, CF was decreased in GLIB-treated control and septic rat hearts and LVDP was more severely depressed in control rat hearts than in septic rat hearts. CROM increased pre-ischemic CF in the septic group although LVDP was unaltered in both groups. After I/R, control rat heart CF was depressed but LVDP completely recovered. Post-ischemic CF in septic rat hearts was elevated compared with vehicle-treated septic rat hearts, but the recovery of LVDP was not improved. These results suggest that K+ATP channels modulate CF in septic rat hearts, but do not mediate cardioprotection as observed in control rat hearts.

Sepsis depresses myocardial function but prevents subsequent ischemia-reperfusion injury. Elevated coronary flow (CF) and endogenous adenosine may be important factors in the complete recovery of postischemic myocardial function observed in septic rat hearts. The purpose of this study was to determine the effects of manipulating CF and of antagonizing adenosine receptors on the postischemic recovery of left ventricular developed pressure (LVDP) in septic and control rat hearts. The relationship between CF and LVDP in septic rat hearts before ischemia was depressed compared with control. However, this relationship was unaltered by ischemia in septic hearts, whereas in control hearts it was severely depressed. Preventing the elevation of CF during reperfusion did not significantly affect the recovery of LVDP in septic rat hearts. Adenosine antagonism by 8-phenyltheophylline (0.1 and 1 nM) prevented the elevated CF during reperfusion, and the higher dose significantly depressed postischemic function. We conclude that elevated CF did not contribute to the recovery of postischemic LVDP in septic rat hearts but that endogenous adenosine may provide protection from ischemia.

During 1994-1996, Shigella sonnei outbreaks occurred in 8 North American traditionally observant Jewish communities. These communities remain relatively separate from neighboring populations while maintaining close contact by travel with coreligionists in other cities. Epidemiologic investigations suggested community-to-community transmission via travel. Outbreak-related and control isolates of S. sonnei from each city were subtyped by pulsed-field gel electrophoresis (PFGE) to confirm an epidemiologic linkage between outbreaks. Forty-three (94%) of 46 outbreak-related isolates had closely related PFGE patterns, constituting a single subtype; 33 (94%) of 35 control isolates demonstrated unrelated PFGE patterns. Several patterns differing by < or = 3 bands were identified within the outbreak subtype; one of these accounted for 65% of outbreak isolates. Hence, a single subtype of S. sonnei caused an international outbreak involving 8 traditionally observant Jewish communities, but not neighboring populations, over a 2-year period, suggesting sustained propagation of the epidemic strain between communities.

The different therapeutic methods for persistent or recurrent hemorrhage due to portal hypertension gastric lesions are discussed from the clinical experience with 5 cases. In 2 cases endoscopic sclerosis was carried out and in one antrectomy was performed with stabilization of the bleeding and improvement in the clinical situation being achieved in long term follow up. Two patients underwent liver transplantation which led to disappearance of the lesions.

One thousand consecutive Brunei Darussalam patients referred with low Hb, and/or low MCV and MCH (Hb < 12.5g/dl, MCV < 76fl, MCH < 27pg) were studied in the laboratory for underlying haemoglobinopathies. 30.0% of such patients were proved to have either beta-thalassaemia trait, beta-thalassaemia major, Hb AE, Hb EE, Hb E beta-thalassaemia or Hb H disease. In some, the haemoglobin abnormality was not identified precisely. Alpha-thalassaemia was suspected in an additional 4.3% of cases but confirmation study by globin-chain synthesis was not available. Beta-thalassaemia trait which was the predominant disorder was equally distributed among the three major race groups of Brunei Darussalam. Hb E was found exclusive among the Malay population. Hb H disease appeared as more common among the Chinese or the Malays (p > 0.05). This study reveals that thalassaemia and haemoglobinopathies are prevalent in Brunei Darussalam.

Intra-oral and extra-oral prosthetic restorations of acquired and developmental defects (oral, para-oral, and facial) have had a fundamental problem of inadequate stability and retention of the prostheses. Application of osseointegration in maxillofacial prosthetic reconstruction followed the positive results obtained by using osseointegrated implants for retaining and supporting maxillary and mandibular dental prostheses. The two case presentations are illustrative examples of the clinical application of osseointegrated implants for maxillofacial reconstructive prosthetic procedures.