Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n = 11) or 40 mg twice a day for 6 weeks. The two dosage groups were well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8.16 +/- 1.15 to 3.53 +/- 0.99 mmol/L (P < .001). The total cholesterol concentration decreased from 9.90 +/- 1.32 to 5.43 mmol/L (P < .001). HDL cholesterol concentration increased from 1.19 +/- 0.31 to 1.49 +/- 0.43 mmol/L (P < .001). Triglyceride concentrations decreased from 1.34 +/- 0.66 to 0.88 +/- 0.36 mmol/L (P < .01). Three subjects had single, transient increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH.     

Large-scale parallel arrays of silicon nanowires via block copolymer directed self-assembly

Extending the resolution and spatial proximity of lithographic patterning below critical dimensions of 20 nm remains a key challenge with very-large-scale integration, especially if the persistent scaling of silicon electronic devices is sustained. One approach, which relies upon the directed self-assembly of block copolymers by chemical-epitaxy, is capable of achieving high density 1?:?1 patterning with critical dimensions approaching 5 nm. Herein, we outline an integration-favourable strategy for fabricating high areal density arrays of aligned silicon nanowires by directed self-assembly of a PS-b-PMMA block copolymer nanopatterns with a L(0) (pitch) of 42 nm, on chemically pre-patterned surfaces. Parallel arrays (5 × 10(6) wires per cm) of uni-directional and isolated silicon nanowires on insulator substrates with critical dimension ranging from 15 to 19 nm were fabricated by using precision plasma etch processes; with each stage monitored by electron microscopy. This step-by-step approach provides detailed information on interfacial oxide formation at the device silicon layer, the polystyrene profile during plasma etching, final critical dimension uniformity and line edge roughness variation nanowire during processing. The resulting silicon-nanowire array devices exhibit Schottky-type behaviour and a clear field-effect. The measured values for resistivity and specific contact resistance were ((2.6 ± 1.2) × 10(5)Ωcm) and ((240 ± 80) Ωcm(2)) respectively. These values are typical for intrinsic (un-doped) silicon when contacted by high work function metal albeit counterintuitive as the resistivity of the starting wafer (～10 Ωcm) is 4 orders of magnitude lower. In essence, the nanowires are so small and consist of so few atoms, that statistically, at the original doping level each nanowire contains less than a single dopant atom and consequently exhibits the electrical behaviour of the un-doped host material. Moreover this indicates that the processing successfully avoided unintentional doping. Therefore our approach permits tuning of the device steps to contact the nanowires functionality through careful selection of the initial bulk starting material and/or by means of post processing steps e.g. thermal annealing of metal contacts to produce high performance devices. We envision that such a controllable process, combined with the precision patterning of the aligned block copolymer nanopatterns, could prolong the scaling of nanoelectronics and potentially enable the fabrication of dense, parallel arrays of multi-gate field effect transistors.     

湖北省蔬菜产业现状与加工业发展建议

文章从区位优势、产业特色和生产水平等特点出发,阐述湖北蔬菜产业的发展现状,剖析其蔬菜产业发展的制约因素,客观分析其蔬菜加工业存在的主要问题,提出全面实施质量标准体系、完善质量卫生安全检测体系、发展蔬菜贮藏保鲜技术和加工工艺等,以促进湖北蔬菜加工产业的可持续健康发展。     

Steady state critical loads of acidity for sulphur and nitrogen: a multi-receptor, multi-criterion approach

The critical load approach to emission reductions has become an important element of the United Nations Economic Commission for Europe (UNECE) Convention on Long-Range Transboundary Air Pollution (CLRTAP). The steady state mass balance approach (SSMB) is the most widely used method in Europe for estimating critical loads, typically applied to forest ecosystems on mineral soils in conjunction with a base cation to aluminium (Bc:Al) ratio using a default critical limit of 1.0. The 'typical' approach has been expanded in this paper by: inclusion of a broader range of natural and semi-natural receptor ecosystems; inclusion of multiple chemical criterion for each receptor; and an attempt to include organic soils (peatlands). Critical loads of acidity were estimated for the Republic of Ireland using four receptor ecosystems (coniferous forest, deciduous forest, natural grasslands and moors and heathlands) and seven chemical criteria. The dominant chemical criteria, in the determination of critical loads, were based on a critical pH limit for mineral soils or a critical pH shift in relation to pristine conditions for organic soils. Approximately 68 and 26% of the final distribution of critical loads were estimated using these criteria, respectively. The 5th-percentile critical loads of acidity were more sensitive than those previously estimated for Ireland due to the inclusion of organic soils. Furthermore, coniferous ecosystems had the lowest critical loads due to the high percentage occurring on organic soils, and the removal of base cations through harvesting. The results demonstrate that it may be more appropriate to use multiple criteria and receptors to ensure adequate protection of biological indicators. However, it is important that appropriate critical limits are chosen to protect the biological indicators and receptor ecosystems from long-term damage.     

Physician decision making and cardiac risk: Effects of knowledge, risk perception, risk tolerance, and fuzzy processing.

Despite training, professionals sometimes make serious errors in risky decision making. The authors investigated judgments and decisions for 9 hypothetical patients at 3 levels of cardiac risk, comparing student and physician groups varying in domain-specific knowledge. Decisions were examined regarding whether they deviated from guidelines, how risk perceptions and risk tolerances determined decisions, and how the latter differed for knowledge groups. More knowledgeable professionals were better at discriminating levels of risk according to external correspondence criteria but committed similar errors in disjunctive probability judgments, violating internal coherence criteria. Also, higher knowledge groups relied on fewer dimensions of information than did lower knowledge groups. Consistent with fuzzy-trace theory, experts achieved better discrimination by processing less information and made sharper all-or-none distinctions among decision categories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Optical alignment-induced errors in holographic particle image velocimetry

A ray-tracing analysis of point-source imaging in the presence of optical misalignment is used to analyze relative image shift as a source of measurement error in holographic particle image velocimetry (HPIV). Although single-reference-beam HPIV is relatively insensitive to optical misalignment, dual-reference-beam systems may suffer substantial errors because of misalignments of the order of microradians. These systems are particularly sensitive to rotations of the hologram about an axis perpendicular to the film and to reconstruction beam misalignment. In a swirling flow experiment, a proposed error-compensation scheme was able to reduce uncertainty from 130% to 10% of the mean measured velocity.     

Bacillus stearothermophilus lctB gene gives rise to functional K+ channels in Escherichia coli and in Xenopus oocytes

We have cloned a small K+ channel subunit (LctB) of the gram-positive bacterium Bacillus stearothermophilus (B. stearo.). The B. stearo. LctB protein is only 134 amino acids long. The sequence contains a typical K+ channel P-domain with a K+ channel GYGD signature sequence and two hydrophobic, possibly membrane-spanning segments M1 and M2. Unexpectedly, LctB K+ channels exhibited properties which differed markedly from the ones reported for KcsA channels of the gram-positive bacterium Streptomyces lividans. LctB channels, when expressed in E. coli, were targeted to the outer membrane and not like KcsA channels to the inner membrane. After reconstitution in black lipid membrane, LctB channels mediated K+ currents at neutral pH. They were apparently not gated by pH like KcsA channels. Also, LctB cRNA produced functional LctB channels in the Xenopus oocyte expression system in marked contrast to KcsA. The results demonstrated that heterologous expression produced functional LctB channels both in E. coli and in Xenopus oocytes. It is proposed that bacterial LctB subunits can be properly handled by the Xenopus oocyte leading to the occurrence of functional LctB K+ channels in the oocyte plasma membrane.     

Packed column supercritical fluid chromatography/mass spectrometry for high-throughput analysis. Part 2

A supercritical fluid chromatograph was previously interfaced to a mass spectrometer (SFC/MS) and the system evaluated for applications requiring high sample throughput using negative-mode atmospheric-pressure chemical ionization (APCI) (Ventura et al. Anal. Chem. 1999, 71, 2410-2416). This report extends the previous work demonstrating the effectiveness of SFC/MS, using positive ion APCI for the analysis of compounds with a wide range of polarities. Substituting SFC/MS for LC/MS results in substantial time saving, increased chromatographic efficiency, and more precise quantitation of sample mixtures. Flow injection analysis (FIA) also benefits from our SFC/MS system. A broader range of solvents is compatible with the SFC mobile phase compared with LC/MS, and solutes elute more rapidly from the SFC/MS system, reducing sample carryover and cycle time. Our instrumental setup also allows for facile conversion between LC/MS and SFC/MS modes of operation.     

High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy

A majority of the human tumor-associated Ags characterized to date are derived from nonmutated "self"-proteins. Little is currently understood about the nature of the self-reactive lymphocytes that recognize these Ags. We recently characterized two nonmutated tumor-associated Ags for the B16 murine melanoma: tyrosinase-related protein-2 (TRP-2) and the endogenous retroviral envelope protein, p15E. We previously reported that both TRP-2 and p15E reactive CTL could be detected in the spleens of naive animals after a single in vitro stimulation using 10(-5)-10(-6) M of the appropriate Kb-binding 9-amino acid epitope. In this report we show that the CTL found in naive animals are low avidity lymphocytes, that respond only to high concentrations of peptide in vitro. We demonstrate that titration of in vitro-stimulating peptide to limiting concentrations distinguishes qualitative differences in the lymphocyte reactivity to these two Ags between vaccinated and unvaccinated animals. We further demonstrate that in vitro expansion of CTL in either high or low concentrations of stimulating peptide generated CTL cultures with different avidities for the relevant epitopes. CTL expanded in low concentrations demonstrated higher avidity for peptide-pulsed targets and better tumor recognition, when compared to CTL generated in the presence of high concentrations of Ag. More importantly, high avidity CTL demonstrated superior in vivo antitumor activity. These results demonstrate that qualitative differences in the CTL that recognize these two self-Ags are critically important to their in vitro and in vivo anti-tumor efficacy.