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Background Coronary heart disease (CHD) is the major cause of early morbidity and mortality in most developed countries. Secondary prevention aims to prevent repeat cardiac events and death in people with established CHD. Lifestyle modifications play an important role in secondary prevention. Yoga has been regarded as a type of physical activity as well as a stress management strategy. Growing evidence suggests the beneficial effects of yoga on various ailments. Objectives To determine the effectiveness of yoga for the secondary prevention of mortality and morbidity in, and on the health-related quality of life of, individuals with CHD. Search methods This is an update of a review previously published in 2012. For this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 1 of 12, 2014), MEDLINE (1948 to February week 1 2014), EMBASE (1980 to 2014 week 6), Web of Science (Thomson Reuters, 1970 to 12 February 2014), China Journal Net (1994 to May 2014), WanFang Data (1990 to May 2014), and Index to Chinese Periodicals of Hong Kong (HKInChiP) (from 1980). Ongoing studies were identified in the metaRegister of Controlled Trials (May 2014) and the World Health Organization International Clinical Trials Registry Platform (May 2014). We applied no language restrictions. Selection criteria We planned to include randomised controlled trials (RCTs) investigating the influence of yoga practice on CHD outcomes in men and women (aged 18 years and over) with a diagnosis of acute or chronic CHD. Studies were eligible for inclusion if they had a follow-up duration of six months or more. We considered studies that compared one group practicing a type of yoga with a control group receiving either no intervention or interventions other than yoga. Data collection and analysis Two authors independently selected studies according to prespecified inclusion criteria. We resolved disagreements either by consensus or by discussion with a third author. Main results We found no eligible RCTs that met the inclusion criteria of the review and thus we were unable to perform a meta-analysis. Authors' conclusions The effectiveness of yoga for secondary prevention in CHD remains uncertain. Large RCTs of high quality are needed.

Many tripartite motif (TRIM) proteins self-associate, forming dimers and higher order complexes. For example, dimers of TRIM5α, a host factor that restricts retrovirus infection, assemble into higher order arrays on the surface of the viral capsid, resulting in an increase in avidity. Here we show that the higher order association of different TRIM proteins exhibits a wide range of efficiencies. Homologous association (self-association) was more efficient than the heterologous association of different TRIM proteins, indicating that specificity determinants of higher order self-association exist. To investigate the structural determinants of higher order self-association, we studied TRIM mutants and chimeras. These studies revealed the following: 1) the RING domain contributes to the efficiency of higher order self-association, which enhances the binding of TRIM5α to the human immunodeficiency virus (HIV-1) capsid; 2) the RING and B-box 2 domains work together as a homologous unit to promote higher order association of dimers; 3) dimerization is probably required for efficient higher order self-association; 4) the Linker 2 region contributes to higher order self-association, independently of effects of Linker 2 changes on TRIM dimerization; and 5) for efficiently self-associating TRIM proteins, the B30.2(SPRY) domain is not required for higher order self-association. These results support a model in which both ends of the core TRIM dimer (RING-B-box 2 at one end and Linker 2 at the other) contribute to the formation of higher order arrays.

Aspergillus fumigatus is a filamentous fungus that can cause severe respiratory disease in immunocompromised individuals. A putative sialidase from A. fumigatus was recently cloned and shown to be relatively poor in cleaving N-acetylneuraminic acid (Neu5Ac) in comparison with bacterial sialidases. Here we present the first crystal structure of a fungal sialidase. When the apo structure was compared with bacterial sialidase structures, the active site of the Aspergillus enzyme suggested that Neu5Ac would be a poor substrate because of a smaller pocket that normally accommodates the acetamido group of Neu5Ac in sialidases. A sialic acid with a hydroxyl in place of an acetamido group is 2-keto-3-deoxynononic acid (KDN). We show that KDN is the preferred substrate for the A. fumigatus sialidase and that A. fumigatus can utilize KDN as a sole carbon source. A 1.45-Å resolution crystal structure of the enzyme in complex with KDN reveals KDN in the active site in a boat conformation and nearby a second binding site occupied by KDN in a chair conformation, suggesting that polyKDN may be a natural substrate. The enzyme is not inhibited by the sialidase transition state analog 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) but is inhibited by the related 2,3-didehydro-2,3-dideoxy-d-glycero-d-galacto-nonulosonic acid that we show bound to the enzyme in a 1.84-Å resolution crystal structure. Using a fluorinated KDN substrate, we present a 1.5-Å resolution structure of a covalently bound catalytic intermediate. The A. fumigatus sialidase is therefore a KDNase with a similar catalytic mechanism to Neu5Ac exosialidases, and this study represents the first structure of a KDNase.

A study was carried out in 11 healthy young men to investigate the pharmacokinetics of chlorpromazine (CPZ) after a bolus intravenous (IV) dose (10 mg) and three single oral doses (25, 50 and 100 mg), with a washout period of two weeks between doses. Plasma levels of CPZ, CPZ N-oxide (CPZNO), CPZ sulfoxide (CPZSO) and both free and conjugated 7-hydroxy-CPZ (7-HOCPZ) were measured by extraction radioimmunoassays. CPZ exhibited multicompartmental pharmacokinetics in most subjects. There was wide between-subject variability in half life (11.05 h), volume of distribution (1215 l), volume of distribution at steady state (642 l) and mean residence time (8.88 h), whereas systemic clearance was somewhat less variable (76.6 l·h−1). All metabolites were present in measurable concentrations in the plasma of 9 of 11 subjects after IV CPZ, whereas free 7-HOCPZ was not detected in the other 2 individuals. With the exception of CPZNO, the biological half lives of the primary metabolites were longer than the half life of CPZ. After oral administration, the percentage of CPZ reaching the systemic circulation intact (F%) was very low (4–38%) and dose dependant. Moreover, both within-subject and between-subject variances were very high. The maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve extrapolated to infinite time (AUC) showed evidence of nonlinearity, whereas half life did not appear to be dose dependant. These data suggest that the high degree of variability in the pharmacokinetics of CPZ is a result of extensive first pass metabolism rather than variation in half life. The mean AUC for the total conjugates of 7-HOCPZ was about two fold higher than that of the parent drug or any other metabolite. This shows that phase II metabolism plays a very significant role in the disposition of CPZ. As a result, the role of CYP2D6 in the 7-hydroxylation of CPZ cannot be fully assessed without taking phase II metabolism into account.

A Case of Rothia dentocariosa Bacteremia in a Patient Receiving Infliximab for Ulcerative Colitis

To review the clinical manifestations of phaeochromocytoma in a Hong Kong Chinese population.Retrospective review. SETTING. Five public hospitals in Hong Kong.Seventeen patients with operated phaeochromocytoma between 1994 and 2003 were reviewed retrospectively.Six patients (35%) were men, 11 (65%) were women. The mean age at presentation was 47 (range, 17-72) years. The diagnosis post-presentation was delayed by 1 to 132 months. Over 70% of the patients had hypertension. The most frequent symptoms were headache (53%), palpitations (53%), and sweating (41%); all these symptoms were present in 24% of the patients. Four (24%) had hereditary phaeochromocytoma/paraganglioma syndrome. The sensitivity of 24-hour urinary catecholamine measurements was 82%. Mean urinary adrenaline and noradrenaline concentrations were respectively 7- and 8-fold greater than the upper reference limits. Computed tomography and metaiodobenzylguanidine scintigraphy were the most widely used means for tumour localisation (sensitivity, 100% and 87% respectively). Approximately 65% of the patients had intra-adrenal tumours; 53% were on right side, 18% were bilateral. All the patients were prescribed phenoxybenzamine (dosage range, 20-120 mg/day) preoperatively. Two thirds of the patients had improved blood pressure 1 year after the operation. No malignancy was reported after a mean follow-up period of 7 years.Our series of patients with phaeochromocytomas commonly had a high frequency of normotension and extra-adrenal tumours. A high index of clinical suspicion and appropriate biochemical investigations are necessary to make the diagnosis, especially for patients manifesting adrenal incidentaloma and extra-adrenal lesion.

ObjectiveTo report the prevalence of anaemia by demographic characteristics and its secular trend over 13 years for south-east Chinese pregnant women, and to determine the focus of anaemia prevention in Chinese pregnant women.DesignProspective study of the data on Hb concentration and other demographic information from a large-scale population-based perinatal health surveillance system in south-east China.SettingFourteen cities or counties in Jiangsu and Zhejiang provinces.SubjectsA total of 467 057 prenatal women who had participated in the perinatal health-care surveillance system and delivered babies from 1 January 1993 to 31 December 2005 and had a record of Hb in all three pregnancy trimesters.ResultsThe overall prevalence of anaemia among pregnant women was 39·6 % from 1993 to 2005. Anaemia prevalence increased from the first (29·6 %) to the second (33·0 %) and third (56·2 %) trimesters. The prevalence of anaemia was higher in villagers, in women with less education and in women with higher gravidity or parity. The prevalence of anaemia in all of the trimesters was higher in the spring, summer and autumn and lower in the winter. The prevalence decreased from 1993 to 2005, from 53·3 % to 11·4 % for the first trimester, 45·6 % to 22·8 % for the second trimester and 64·6 % to 44·6 % for the third trimester.ConclusionsThe prevalence of anaemia among pregnant women in Jiangsu and Zhejiang provinces decreased substantially from 1993 to 2005. However, anaemia in the third trimester is still a severe public health problem among pregnant women in these areas.

A gene encoding a putative sialidase was identified in the genome of the opportunistic fungal pathogen, Aspergillus fumigatus. Computational analysis showed that this protein has Asp box and FRIP domains, it was predicted to have an extracellular localization, and a mass of 42 kDa, all of which are characteristics of sialidases. Structural modeling predicted a canonical 6-bladed beta-propeller structure with the model's highly conserved catalytic residues aligning well with those of an experimentally determined sialidase structure. The gene encoding the putative Af sialidase was cloned and expressed in Escherichia coli. Enzymatic characterization found that the enzyme was able to cleave the synthetic sialic acid substrate, 4-methylumbelliferyl alpha-D-N-acetylneuraminic acid (MUN), and had a pH optimum of 3.5. Further kinetic characterization using 4-methylumbelliferyl alpha-D-N-acetylneuraminylgalactopyranoside revealed that Af sialidase preferred alpha2-3-linked sialic acids over the alpha2-6 isomers. No trans-sialidase activity was detected. qPCR studies showed that exposure to MEM plus human serum induced expression. Purified Af sialidase released sialic acid from diverse substrates such as mucin, fetuin, epithelial cell glycans and colominic acid, though A. fumigatus was unable to use either sialic acid or colominic acid as a sole source of carbon. Phylogenetic analysis revealed that the fungal sialidases were more closely related to those of bacteria than to sialidases from other eukaryotes.

A scattering technique is described in which the incident laser beam is tightly focused to isolate the effects of a single particle. In this way the individual particles may be studied in their natural environment, and experiments with latex spheres are in agreement with the theory.

Thin-film PbTe diode lasers are used for Doppler-limited Stark spectroscopy on the nu(4) vibration-rotation band of NH(3) in the 1545-1595-cm(-1) region. The lasers operate cw below 20 K and are frequency tuned by varying the diode current. The nu(4) excited state dipole moment of NH(3) is found to be about 1% less than the ground state value.

This paper sets out a revised view of the classical diagonal dominance method for multivariable feedback systems. The various types of dominance measure are unified by using one fundamental dominance theorem (FD)l. It is shown that the fundamental dominance condition yields the smallest dominance measure when compared with all the known classical diagonal dominance measures. In addition it is shown that the dominance measures such as row/column, generalized dominance and a few new ones are special cases and can be derived from this same FD theorem. This improved dominance criterion also provides the sufficient condition for a system to be approximated by a nominal one in the sense that the stabilization of this nominal system will assure the stability of the original one. Finally, a new type of dominance measure named L-dominance is presented. It has been shown that this new approach yields an even smaller dominance measure, and that when it is applied to matrices with non-positive off-diagonal elements, ...

Thin copper films were grown on glass by pulsed-laser deposition. The simultaneous in situ monitoring of the electrical resistance and optical transmittance of the growing film yielded highly reproducible and consistent data about percolation onset and film conductivity, both being useful indicators of film quality. When prepared under favorable conditions, films as thin as 1.5 nm would percolate, and became fully continuous at 5 nm, with conductivity reaching 30% of that of bulk copper.

The effects of vacuum annealing on the structural and transport properties of the La0.67Ca0.33MnO3−δ films grown on SrTiO3 (LCMO/STO) and NdGaO3 (LCMO/NGO) substrates have been studied. A lattice expansion due to oxygen release during the annealing is observed. Under the same condition, the change of the out-of-plane lattice parameter in LCMO/STO is two to three times larger than that in LCMO/NGO, indicating a strong tendency for the oxygen in the former to escape. Correspondingly, the metal-to-semiconductor transition shifts to lower temperatures, linearly with lattice constant until a critical value, Δd=0.03 A for LCMO/STO and Δd=0.05 A for LCMO/NGO, after which a sudden drop of the transition temperature to zero occurs. The different lattice strains in both films are presumably responsible for the different critical oxygen contents for the occurrence of the resistive transition.

Viral hepatitis poses important problems for children. In preschoolers, hepatitis A virus (HAV) infection frequently causes acute liver failure. Vaccinating toddlers against HAV in countries with high endemicity is expected to decrease mortality. HAV vaccine demonstrates efficacy (comparable to immunoglobulin) as post-exposure prophylaxis. A recently developed vaccine against hepatitis E virus (HEV) may benefit fetal health, because pregnant women are most prone to acute liver failure as a result of HEV. Hepatitis B vaccine continues to demonstrate value and versatility for preventing serious liver disease. With chronic infection, undetectable levels of serum HBV DNA complement e-seroconversion as the preferred outcome measure; suppressed viral load correlates with long-term complications better than HBeAg status. Among Taiwanese children, low pretreatment HBV DNA (

Orlistat is a gastrointestinal lipase inhibitor approved for use in obesity. So far, no evidence has been reported on the use of orlistat in obese patients with coronary artery disease (CAD).To investigate the effect of orlistat on body weight and lipid profiles in obese patients with CAD and hypercholesterolemia.Thirty non-diabetic patients with CAD, body mass index (BMI)or = 25 kg/m(2) and low-density lipoprotein cholesterol (LDL-C)or = 2.6 and4.1 mmol/L were put on diet for 12 weeks. Those still having a BMIor = 25 kg/m(2) received orlistat 120 mg thrice daily for another 24 weeks.BMI was significantly reduced by 1.7% after 12 weeks of dietary treatment. The 24-week orlistat treatment resulted in further significant reduction in BMI (-2.8%) and LDL-C (-7.0%).Diet and orlistat treatment significantly reduced BMI and improved LDL-C in obese patients with CAD and hypercholesterolemia.

This paper firstly reports key factors which are to be necessarily considered for the successful two-bit (four-level) cell operation in a phase-change random access memory (PRAM). They are: 1) the write-and-verify (WAV) writing of four-level resistance states; and 2) the moderate-quenched (MQ) writing of intermediate resistance levels, 3) the optimization of temporal resistance increase (so-called resistance drift) and 4) of resistance increase after thermal annealing. With taking into account of them, we realized a two-bit cell operation in diode-switch phase change memory cells with 90 nm technology. All of four resistance levels are highly write endurable and immune to write disturbance above 108 cycles, respectively. In addition, they are non-destructively readable above 107 read pulses at 100 ns and 1 uA.

To develop and validate a sensitive and specific HPLC assay for cladribine (CdA) in plasma for pharmacokinetic studies in rats.CdA and the internal standard AZT were purchased from Sigma-Aldrich Chem. The HPLC system consisted of a Shimadzu LC-9A pump, a 3 im, 250 x 2.0 mm I.D. high speed C18 column (Jupitertrade mark), preceded by a 5 im 4 4 mm I.D. C18 guard column (Licrocarttrade mark), an Agilent Model 1050 UV-VIS detector and a 3395 Integrator. The mobile phase was made up of 0.01M KH2PO4 (pH 5): methanol: acetonitrile 90:5:5). The system was operated at ambient temperature with a flow rate of 0.3 mL/min, and UV wavelength at 265 nm, and an operating pressure of ca. 1.56 kpsi. Extraction of cladribine and AZT from plasma was achieved by solid phase extraction using 100 mg/mL C18 SPE columns Extra-septrade mark). The assay was validated for sensitivity, precision, specificity and application for pharmacokinetic study in rats.Under these conditions, the average retention times of CdA and AZT were 13.5 and 21 min, respectively, and recoveries were between 80 - 95%. Standard curve constructed from plasma standards was linear from 0.1 ug/mL to 1 ug/mL with regression coefficient (r2) 0.99 or greater. Sensitivity assessed by on column injection was1 ng. Using a 50-uL plasma sample size, the mean intra assay variations 0.1 ug/mL were 7%, and inter assay variations over a period of 3 months for 5 separate batches were less than 20%. The assay was used to study a single dose pharmacokinetic study of CdA in rats after a 2 mg/kg subcutaneous injection.The described HPLC assay has adequate sensitivity and specificity to study pharmacokinetics of CdA in rats, and could be adapted also to clinical pharmacokinetic studies.

Although conventional non-pharmacological and pharmacological treatments for insomnia are effective in many people, alternative therapies such as acupuncture are still widely practiced. However, it remains unclear whether the existing evidence is rigorous enough to support its use.To determine the efficacy and safety of acupuncture in people with insomnia.We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, Dissertation Abstracts International, CINAHL, AMED (the Allied and Complementary Medicine Database), TCMLARS (Traditional Chinese Medical Literature Analysis and Retrieval System), National Center for Complementary and Alternative Medicine, the National Institute of Health Clinical Trials Database, the Chinese Acupuncture Trials Register, the Trials Register of the Cochrane Complementary Medicine Field, from inception to 2006, and the sleep bibliography, which is available at www.websciences.org/bibliosleep. We searched reference lists of retrieved articles, and contacted trial authors and experts in the field for information on ongoing/completed trials.Randomised controlled trials evaluating any form of acupuncture involving participants of any age with any type of insomnia were included. Included trials compared acupuncture with placebo or sham or no treatment, or acupuncture plus other treatments compared with the same other treatments. Trials that compared only acupuncture methods or compared acupuncture alone against other treatments alone were excluded, since they did not yield the net effect of acupuncture.Two review authors independently extracted data and assessed quality according to a set of criteria for risk of selection bias, performance bias, attrition bias and detection bias. Relative risk (RR) and standardised mean difference (SMD) with 95% confidence intervals were used for binary and continuous outcomes respectively. Data were combined in meta-analyses (on an intention-to-treat basis), where more than one trial without significant clinical heterogeneity presented the same outcome.Seven trials met the inclusion criteria. The studies included 590 participants with insomnia, of whom 56 dropped out. Participant age ranged from 15 to 98 years, and the duration of insomnia varied from 6 months to 19 years. Co-existing medical conditions contributing to insomnia included stroke, end-stage renal disease and pregnancy. Apart from conventional needle acupuncture, different variants of acupuncture such as acupressure, auricular magnetic and seed therapy, and transcutaneous electrical acupoint stimulation (TEAS) were evaluated. Meta-analysis was limited because of considerable heterogeneity between comparison groups and between outcome measures. Based on the findings from individual trials, the review suggested that acupuncture and acupressure may help to improve sleep quality scores when compared to placebo (SMD = -1.08, 95% CI = -1.86 to -0.31, p=0.006) or no treatment (SMD -0.55, 95% CI = -0.89 to -0.21, p=0.002). TEAS also resulted in better sleep quality score in one trial (SMD = -0.74, 95% CI = -1.22 to -0.26, p=0.003). However, the efficacy of acupuncture or its variants was inconsistent between studies for many sleep parameters, such as sleep onset latency, total sleep duration and wake after sleep onset. The combined result from three studies reporting subjective insomnia improvement showed that acupuncture or its variants was not more significantly effective than control (RR = 1.66, 95% CI = 0.68 to -4.03) and significant statistical heterogeneity was observed. Only one study reported an adverse event, with one out of 16 patients (6.3%) withdrawing from acupuncture because of pain.The small number of randomised controlled trials, together with the poor methodological quality and significant clinical heterogeneity, means that the current evidence is not sufficiently extensive or rigorous to support the use of any form of acupuncture for the treatment of insomnia. Larger high quality clinical trials employing appropriate randomisation concealment and blinding with longer follow-up are needed to further investigate the efficacy and safety of acupuncture for the treatment of insomnia.

Programming with larger current than optimized one is often preferable to ensure a good resistance distribution of high-resistive reset state in high-density phase-change random access memories because it is very effective to increase the resistance of cells to a target value. In this paper, we firstly report that this larger current writing may conversely degrade the reset distribution by reducing the resistance of normal cells via the partial crystallization of amorphous Ge2Sb2Te5 and this degradation can be suppressed by designing a novel cell structure with a heat dissipating layer.

In owl monkeys, the typical retroviral restriction factor of primates, TRIM5α, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIM5 RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection.

Fully functional 512Mb PRAM with 0.047mum2 (5.8F2) cell size was successfully fabricated using 90nm diode technology in which the authors developed novel process schemes such as vertical diode as cell switch, self-aligned bottom electrode contact scheme, and line-type Ge2Sb2Te5. The 512Mb PRAM showed excellent electrical properties of sufficiently large on-current and stable phase transition behavior. The reliability of the 512Mb chip was also evaluated as a write-endurance over 1E5 cycles and a data retention time over 10 years at 85degC

To assess the prevalence of macroalbuminuria and microalbuminuria, and the level of blood pressure control in patients with type 2 diabetes and hypertension in Hong Kong.Cross-sectional clinic-based epidemiological study.Six medical centres (including two public hospital diabetes centres) in Hong Kong.Recruited from the medical centres from April to November 2002, after excluding those with bacteriuria and haematuria.Body mass index; blood pressure; levels of blood glucose, macroalbuminuria, and microalbuminuria; treatments for hypertension and diabetes.The as per-protocol recruited population of 437 hypertensive type 2 diabetic patients had a mean age of 61.7 (standard error, 0.5) years. Overall, the prevalence of diabetic nephropathy in this population was high; 18.3% had macroalbuminuria (95% confidence interval, 16.5-20.2%) and 24.9% had microalbuminuria (95% confidence interval, 22.9-27.0%). Predictive factors were advanced age, male sex, poor blood pressure control, and existing cardiovascular complications. Whilst almost all patients (96.1%) were receiving treatment for hypertension, only 25.6% had systolic/diastolic blood pressures below the 130/85 mm Hg target.In Hong Kong, the prevalence of microalbuminuria and macroalbuminuria is high in type 2 diabetic patients with hypertension, particularly in males and those with poorly controlled systolic blood pressure. Tight glycaemic control, antihypertensive therapy, and use of renin-angiotensin system inhibitors/blockers are necessary to retard the progression of nephropathy to advanced renal disease.

The present study uses cell-based screening assays to assess the anticancer effects of targeting phosphatidylinositol 3-kinase–regulated integrin-linked kinase (ILK) in combination with small-molecule inhibitors of Raf-1 or mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK). The objective was to determine if synergistic interactions are achievable through the use of agents targeting two key cell signaling pathways involved in regulating glioblastoma cancer. The phosphatidylinositol 3-kinase/protein kinase B (PKB)/Akt and the Ras/MAPK pathway were targeted for their involvement in cell survival and cell proliferation, respectively. The glioblastoma cell lines U87MG, SF-188, and U251MG were transiently transfected with an antisense oligonucleotide targeting ILK (ILKAS) alone or in combination with the Raf-1 inhibitor GW5074 or with the MEK inhibitor U0126. Dose and combination effects were analyzed by the Chou and Talalay median-effect method and indicated that combinations targeting ILK with either Raf-1 or MEK resulted in a synergistic interaction. Glioblastoma cells transfected with ILKAS exhibited reduced levels of ILK and phosphorylated PKB/Akt on Ser473 but not PKB/Akt on Thr308 as shown by immunoblot analysis. These results were confirmed using glioblastoma cells transfected with ILK small interfering RNA, which also suggested enhanced gene silencing when used in combination with U0126. U87MG glioblastoma cells showed a 90% (P < 0.05) reduction in colony formation in soft agar with exposure to ILKAS in combination with GW5074 compared with control colonies. A substantial increase in Annexin V–positive cells as determined by using fluorescence-activated cell sorting methods were seen in combinations that included ILKAS. Combinations targeting ILK and components of the Ras/MAPK pathway result in synergy and could potentially be more effective against glioblastoma cancer than monotherapy. [Mol Cancer Ther 2006;5(3):645–54]

Numerous mouse models of prostate carcinogenesis have been developed, but hitherto there has been no model in which the prostate gland could be imaged in live animals. The transgenic model generated here targeted mouse prostate gland using a firefly luciferase enzyme under the control of a small but highly active and specific supra prostate-specific antigen (sPSA) promoter. We evaluated postnatal prostate development, involution and androgen-induced restoration of prostate growth in adult transgenic mice using bioluminescence imaging. Results of our study showed that: (i) the prostate gland of male offspring did not yield a significant bioluminescence signal until after sexual maturity. Luciferase was detected in the luminal epithelial cells of the ventral and dorsolateral lobes of the prostate gland and caput epididymis, with little or no activity in 18 other organs evaluated. (ii) While a constant high level of bioluminescence was detected in the mouse prostate from 5 to 35 weeks of age, a slight drop in bioluminescence was detected at 36 to 54 weeks. (iii) Upon castration, the luciferase activity signal associated with mouse prostate detected by a cooled charge-coupled device camera was dramatically reduced. This signal could be rapidly restored to pre-castration levels after androgen administration. Androgen-induced luciferase activity subsided to nearly basal levels 5 days following the last injection. These data demonstrate that a bioluminescent mouse model with luciferase activity restricted to the prostate gland under the control of a (sPSA) promoter can be used on a real-time basis in live animals to investigate the development and responsiveness of the prostate gland to exogenously administered androgen. This model can be extended to detect the responsiveness of the prostate gland to therapy and used as a founder strain to visualize tumors in hosts with different genetic backgrounds.

Pharmacyclics is developing the photosensitizer, motexafin lutetium as Antrin for the potential treatment of restenosis and atherosclerotic plaques, Lutrin for the possible treatment of cancer, and Optrin for the possible treatment of age-related macular degeneration (AMD). ANTRIN: A phase II multicenter, randomized, controlled study involving 375 peripheral artery disease (PAD) patients is being conducted in the US. It is designed to evaluate Antrin photoangioplasty as a primary treatment for PAD and for the prevention of restenosis following balloon angioplasty [341341,347151]. LUTRIN: Lutrin is being developed for the possible treatment of a number of cancers [348919]. In July 1997, the compound entered phase II trials for breast cancer [323952,323929]. In August 2000, the compound was undergoing a phase IIb trial for advanced refractory breast cancer [380234]. OPTRIN: In May 2000, Pharmacyclics reported preliminary results from an ongoing phase II dose-ranging study with Optrin for the photodynamic therapy of patients with AMD [365074].

Objectives – Danshen, a Chinese herb, has been used as a standard treatment for acute ischaemic stroke in China. This study assesses the quality of all randomized control trials (RCTs) comparing Danshen of any preparation to without Danshen (placebo or other western or herbal medicines), and to evaluate its effectiveness in improving disability. Materials and methods – Systematic review through literature search in MEDLINE, Cochrane Library, China Biological Medicine Database and others. The main outcome measure is disability improvement on the Chinese National Disability Scale (CNDS) at 2 weeks after intervention. Results – Of 33 Danshen control trials for acute ischaemic stroke identified in the literature, none were placebo-controlled. Eleven RCTs comparing Danshen with one of seven Western and two herbal medicines met the inclusion criteria for review, however, these studies were of poor quality. Compared with the nine medicines, the effect of Danshen was inferior in five trials and not significantly different in another six trials. For the two trials comparing Danshen with Buflomedil, the combined odds ratio (OR) was 0.27 (95% CI: 0.12–0.61) favouring Buflomedil, but the test of homogeneity revealed heterogeneity (P = 0.083). For the two trials comparing Danshen with Naloxone, the combined OR was 0.16 (95% CI: 0.07–0.40) favouring Naloxone. However, none of the nine medicines per se has been proven effective in post-stroke disability improvement. Conclusions – The existing Danshen RCTs are not placebo-controlled and are of poor quality, therefore, there is no substantial evidence that Danshen is effective. Systematic review on RCTs comparing Danshen with other medicines does not support the notion that Danshen may be beneficial to disability improvement after acute ischaemic stroke.

To examine the nutritional status of older Tibetans in rural China.Cross sectional study.Remote mountainous region of Sichuan province of Western China.Forty four male and forty six female Tibetans, over 60 years old were recruited. Body weight, standing height, triceps and bicep skinfold thicknesses (TSF, BSF), mid arm circumference (MAC) and waist circumference (WC) were measured. Dietary intakes were assessed by a twenty-four hour dietary recall. Based on skinfold thicknesses and MAC, total body fat and corrected arm muscle area (CAMA) were calculated by published equations. Their nutritional status and dietary intakes were compared with those of normal older people in Hong Kong and a rural area near Tianjin in the east coast of China.Compared with Hong Kong older women, the Tibetan older women had similar BMI and total body fat, but their CAMA was significantly greater (p0.01). The Tibetan older men had lower BMI, total body fat (p0.05), and higher CAMA than the Hong Kong older men (p0.05). The average calorie intake in the Tibetans was lower than that of older people in Hong Kong and rural Tianjin. Intakes of protein, vitamins and minerals were the lowest in Tibetans and the highest in older people in Hong Kong.Older Tibetans had more lean mass than Hong Kong older Chinese despite having lower caloric and protein intakes. Older Tibetan women were fatter than their male counterparts, and they were as fat as the older people in Hong Kong, despite having low caloric intakes.

PRAM is a promising memory that can solve the problems of conventional memory. Writing current reduction is the most important technical challenges in order to maximize the advantage of PRAM in scaling. We will present the high density 64Mb PRAM based on 0.18 /spl mu/m CMOS technologies. And Various approaches to reduce the writing Current will be reviewed.

PRAM(Phase-Change RAM) is a promising memory that can solve the problems of conventional memory and has the nearly ideal memory characteristics. We reviewed the issues for high density PRAM integration. Writing current reduction is the most urgent problem for high density PRAM realization. We presented process factors which affect the writing current and the result of improvement. Finally we demonstrated results of 64Mb PRAM integration based on 0.18/spl mu/m CMOS technology.

By developing a chalcogenide memory element that can be operated at low writing current, we have demonstrated the possibility of high-density phase-change random access memory. We have investigated the phase transition behaviors as a function of various process factors including contact size, cell size and thickness, doping concentration in chalcogenide material and cell structure. As a result, we have observed that the writing current is reduced down to 0.7 mA.

DP-b99 is a derivative of the calcium chelator BAPTA that is under development as a neuroprotectant for the potential treatment of stroke, head trauma and neurological damage associated with coronary artery bypass graft. By March 2003, phase II clinical trials in acute stroke and traumatic brain injury were ongoing.

With respect to the operation of a Phase-change Random Access Memory (PRAM or PcRAM), we studied the effect of the contact between the electrode metal and the chalcogenide glass, N2 doped Ge2Sb2Te5 in this report. We investigated a change of the resistance-programming current pulse (R-I) curve varying the contact size and the electrode material. Also we tested the surface oxidation of the electrode. We found that the programming current, the resistance of the programmed state (“RESET”) and the erased state (“SET”) were highly dependent on the above parameters. These results are presented and a more effective way to the high density PRAM will be proposed.

This article reviews the available data on the study of iodine deficiency disorders in Hong Kong and to discuss the approach towards preventing such disorders in Hong Kong. The importance of iodine and iodine deficiency disorders is described, and the available data on the dietary iodine intake and urinary iodine concentration in different populations of Hong Kong are summarised and discussed. Dietary iodine insufficiency among pregnant women in Hong Kong is associated with maternal goitrogenesis and hypothyroxinaemia as well as neonatal hypothyroidism. Borderline iodine deficiency exists in the expectant mothers in Hong Kong. Women of reproductive age, and pregnant and lactating women should be made aware and educated to have an adequate iodine intake, such as iodised salt, as an interim measure. A steering group involving all stakeholders should be formed to advise on the strategy of ensuring adequate iodine intake, including universal iodisation of salt in Hong Kong. Continuous surveillance of iodine status in the Hong Kong population is necessary.

To determine whether clinical outcomes in patients with type 2 diabetes were improved by protocol-driven care in a Diabetes Centre compared with usual outpatient care.Descriptive analysis of a prospective cohort.During a median 7-year observational period, 91 patients with type 2 diabetes and no cardiovascular or renal complications were monitored by a nurse and a diabetologist in a clinical trial setting according to a structured protocol. Another 81 patients with comparable clinical characteristics were monitored by generalists at the medical clinic in the same hospital. Clinical end points, defined as death and cardiovascular and renal events, were evaluated in 1997 by review of case records.Patients receiving structured care had lower mortality (relative risk [RR] = 0.21; 95% confidence interval [CI] = 0.07, 0.65; P = .006) than the usual-care group, as well as a lower incidence of combined clinical end points (RR = 0.43; 95% CI = 0.22, 0.84; P = .01). In the usual-care group, patients who had no monitoring of glycosylated hemoglobin or plasma lipid levels during the entire observational period (8.6%) had a 14.6-fold (P.01) and 15.7-fold (P.01) increased risk of death and combined clinical end points, respectively, compared with those who had at least one measurement (60.5%).Management by protocol-driven care model improved survival and clinical outcomes in patients with type 2 diabetes. Definitive studies are required to confirm these findings and compare the cost effectiveness of these care models.

GEM-231 (HYBO-165) is an 18mer hybrid oligonucleotide under development by Hybridon for the potential treatment of cancer. Phase I/II dose-escalation trials of GEM-231 in combination with paclitaxel and docetaxel were ongoing in March 2002. At this time, a phase I/II trial of GEM-231 in combination with irinotecan (CPT-11) was initiated in patients with solid tumors. As of February 2003, Hybridon planned to initiate phase II trials in 2003.

The authors report on failure analysis results on miniaturized multilayer ceramic capacitors ('0402', '0603', '0805', and '1206' sizes) which have been subjected to various degrees of thermal shock up to 450/spl deg/C by ice-water or dry-ice quenching. The thermal shock resistance of '0402' multilayer ceramic capacitors is found to be about 400/spl deg/C and considerably better than that of the larger ones. Microstructural and layer-by-layer insulation resistance analyses have clearly identified the physical locations responsible for the electrical leakage of defective capacitors. No evidence of silver migration as a dominant failure mechanism has been observed for any of the defective capacitors under usual operating stresses. Comparisons of I-V characteristics for multilayer ceramic capacitors quenched by ice water and dry ice confirm that water plays a significant role in causing electrical failure at nominal bias. Failure mechanisms are then proposed to explain the failure of miniaturized multilayer ceramic capacitors under normal service conditions. >

In this paper, the electrical behavior of multilayer ceramic capacitors (MLCs) in strict dynamic high temperature-humidity-DC bias voltage (THB) conditions were studied and the failure model of MLCs under such conditions was proposed. It was found, if the environmental temperature and humidity rose too fast and the temperature of a MLC was lower than the dew point temperature of surrounding moist air, dewdrops would condense on the MLC surface. When DC voltage was applied, metallic ions from end terminations of the MLC would migrate along the condensed water film on the MLC surface and made a permanent short-circuiting path between two terminations. Silver and tin migrations were found by EDX detection in our experiment. It was also found that the applied DC electrical loading level had a strong influence on the fail rate of MLCs. The recovery rate of MLCs after the dynamic THB process decreased with applied DC voltage increasing. To reduce the effect of dewdrops of moist air on the reliability of MLCs, the method and speed of temperature and humidity rise are discussed. >

Because of limited server and network capacities in multimedia streaming, proxies are commonly used to cache multimedia objects such that, by accessing nearby proxies, clients can enjoy smaller start-up latencies and reduced packet loss and delay jitters for their requests. However, the use of video proxies increases the risk that multimedia data are exposed to unauthorized access by intruders. In this paper, we present a framework for implementing a secure video proxy or, more generally, a secure proxy architecture. The framework employs a notion of asymmetric reversible parametric sequences to provide the following security properties: (1) data confidentiality during transmission, (2) end-to-end data confidentiality, (3) data confidentiality against proxy intruders, and (4) data confidentiality against member collusion. Our framework is grounded on a multi-key RSA technique such that system resilience against attacks is provably strong given standard computability assumptions. We also propose the use of a set of encryption configuration parameters to trade off proxy encryption throughput against the viewing quality of video by unauthorized parties. Implementation results on a Pentium III/800 MHz machine show that our techniques can simultaneously achieve high encryption throughput and extremely low video quality (in terms of both PSNR and the visual quality of decoded frames) during unauthorized viewing.

Cyano-mediated interaction of the alternating high-spin Mn(II) centers and low-spin Ru(III) centers in {Mn[Ru(acac)2 (CN)2 ]2 }n (Hacac=acetylacetone) results in long-range ferromagnetic ordering below 3.6 K. This novel Mn(II) Ru(III) coordination polymer, which has a diamond-like structure, was constructed from [Ru(acac)2 (CN)2 ](-) and Mn(2+) ions.

As less arteriography is performed before carotid surgery, concern arises about missing occult cerebral aneurysms and possible adverse outcomes. A study was conducted by the divisions of vascular surgery and neurosurgery of Northwestern University Medical School to evaluate the frequency of incidental cerebral aneurysms and outcomes of patients with extracranial cerebrovascular disease and asymptomatic cerebral aneurysms. From October 1995, through March 1997, 200 patients underwent intracranial and extracranial cerebrovascular angiography for evaluation of extracranial disease. Demographic data, symptoms, data of vascular lesions, surgical treatment and outcomes of stroke and death were recorded prospectively. Two patients (1%) had asymptomatic cerebral aneurysms found on angiography. Six more patients were referred with a known asymptomatic cerebral aneurysm with extracranial disease during this same period. Of these eight patients, five underwent extracranial vascular reconstruction surgery and seven received treatment for their aneurysms. There were two stroke complications, both occurred after treatment of a basilar artery aneurysm. One of these patients died. No aneurysms ruptured following 203 extracranial revascularizations during this same period. On the basis of the low prevalence of diagnosing coincidental cerebral aneurysms during work-up of extracranial disease, as well as the lack of evidence that carotid surgery predisposes to aneurysm rupture in these patients in both our study and the literature review, it is concluded that coexisting extracranial disease and asymptomatic cerebral aneurysms do not pose a case against carotid surgery without routine arteriography. However, arteriography should be considered in selected groups of patients where the yield of intracranial aneurysms is high; these include patients with a familial history of cerebral aneurysms, autosomal dominant polycystic kidney disease, extracranial internal carotid artery medial fibrodysplasia, Takayasu's arteritis, alpha1-antitripsin deficiency and atypical clinical presentations, including headache.