应用于室内空气过滤的新型过滤介质

论述了关于商用和住宅HVAC、便携式空气净化器和真空吸尘器的最新过滤介质创新技术,利用该技术可达到MERV 16过滤水平而压降低于MERV 10过滤器。与其他商品过滤器相比,由该性能优良的介质制成的便携式空气净化器可使HEPA的CADA提高10%~30%;真空吸尘器使用由新研发的过滤介质制成的过滤器,其性能有极大的提高。     

Identification of a Small‐Molecule Inhibitor of HIV‐1 Assembly that Targets the Phosphatidylinositol (4,5)‐bisphosphate Binding Site of the HIV‐1 Matrix Protein

The development of drug resistance remains a critical problem for current HIV‐1 antiviral therapies, creating a need for new inhibitors of HIV‐1 replication. We previously reported on a novel anti‐HIV‐1 compound, N²‐(phenoxyacetyl)‐N‐[4‐(1‐piperidinylcarbonyl)benzyl]glycinamide ( 14 ), that binds to the highly conserved phosphatidylinositol (4,5)‐bisphosphate (PI(4,5)P₂) binding pocket of the HIV‐1 matrix (MA) protein. In this study, we re‐evaluate the hits from the virtual screen used to identify compound 14 and test them directly in an HIV‐1 replication assay using primary human peripheral blood mononuclear cells. This study resulted in the identification of three new compounds with antiviral activity; 2‐(4‐{[3‐(4‐fluorophenyl)‐1,2,4‐oxadiazol‐5‐yl]methyl})‐1‐piperazinyl)‐N‐(4‐methylphenyl)acetamide ( 7 ), 3‐(2‐ethoxyphenyl)‐5‐[[4‐(4‐nitrophenyl)piperazin‐1‐yl]methyl]‐1,2,4‐oxadiazole ( 17 ), and N‐[4‐ethoxy‐3‐(1‐piperidinylsulfonyl)phenyl]‐2‐(imidazo[2,1‐b][1,3]thiazol‐6‐yl)acetamide ( 18 ), with compound 7 being the most potent of these hits. Mechanistic studies on 7 demonstrated that it directly interacts with and functions through HIV‐1 MA. In accordance with our drug target, compound 7 competes with PI(4,5)P₂ for MA binding and, as a result, diminishes the production of new virus. Mutation of residues within the PI(4,5)P₂ binding site of MA decreased the antiviral effect of compound 7 . Additionally, compound 7 displays a broadly neutralizing anti‐HIV activity, with IC₅₀ values of 7.5–15.6 μM for the group M isolates tested. Taken together, these results point towards a novel chemical probe that can be used to more closely study the biological role of MA and could, through further optimization, lead to a new class of anti‐HIV‐1 therapeutics.     

Pathomechanisms in the Kidneys in Selected Protozoan Parasitic Infections

Leishmaniasis, malaria, toxoplasmosis, and acanthamoebiasis are protozoan parasitic infections. They remain important contributors to the development of kidney disease, which is associated with increased patients’ morbidity and mortality. Kidney injury mechanisms are not fully understood in protozoan parasitic diseases, bringing major difficulties to specific therapeutic interventions. The aim of this review is to present the biochemical and molecular mechanisms in kidneys infected with Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Acanthamoeba spp. We present available mechanisms of an immune response, oxidative stress, apoptosis process, hypoxia, biomarkers of renal injury in the serum or urine, and the histopathological changes of kidneys infected with the selected parasites. Pathomechanisms of Leishmania spp. and Plasmodium spp. infections have been deeply investigated, while Toxoplasma gondii and Acanthamoeba spp. infections in the kidneys are not well known yet. Deeper knowledge of kidney involvement in leishmaniasis and malaria by presenting their mechanisms provides insight into how to create novel and effective treatments. Additionally, the presented work shows gaps in the pathophysiology of renal toxoplasmosis and acanthamoebiasis, which need further research.     

(R)-(-)- and (S)-(+)-Synadenol: synthesis, absolute configuration, and enantioselectivity of antiviral effect

Synthesis of (R)-(-)- and (S)-(+)-synadenol (1a and 2a, 95-96% ee) is described. Racemic synadenol (1a + 2a) was deaminated with adenosine deaminase to give (R)-(-)-synadenol (1a) and (S)-(+)-hypoxanthine derivative 5. Acetylation of the latter compound gave acetate 6. Reaction with N, N-dimethylchloromethyleneammonium chloride led to 6-chloropurine derivative 7. Ammonolysis furnished (S)-(+)-synadenol (2a). Absolute configuration of 1a was established by two methods: (i) synthesis from (R)-methylenecyclopropanecarboxylic acid (8) and (ii) X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. Racemic methylenecyclopropanecarboxylic acid (10) was resolved by a modification of the described procedure. The R-enantiomer 8 was converted to ethyl ester 13 which was brominated to give vicinal dibromides 14. Reduction with diisobutylaluminum hydride then furnished alcohol 15 which was acetylated to the corresponding acetate 16. Alkylation-elimination procedure of adenine with 16 yielded acetates 17 and 18. Deprotection with ammonia afforded a mixture of Z- and E-isomers 1a and 19 of the R-configuration. Comparison with products 1a and 2a by chiral HPLC established the R-configuration of (-)-synadenol (1a). These results were confirmed by X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. The latter forms a pseudosymmetric dimer with adenine-adenine base pairing in the lattice with the nucleobase in an anti-like conformation. Enantiomers 1a and 2a exhibit varied enantioselectivity toward different viruses. Both enantiomers are equipotent against human cytomegalovirus (HCMV) and varicella zoster virus (VZV). The S-enantiomer 2a is somewhat more effective than R-enantiomer 1a in herpes simplex virus 1 and 2 (HSV-1 and HSV-2) assays. By contrast, enantioselectivity of antiviral effect is reversed in Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1) assays where the R-enantiomer 1a is preferred. In these assays, the S-enantiomer 2a is less effective (EBV) or devoid of activity (HIV-1).     

On the phase transition in Na0.5 Bi0.5 TiO3

The existence of polar regions in Na_0.5Bi_0.5Tio₃ and pyroelectric measurements. Both dynamics and sizes of these regions depend on temperature and time.     

Modeling power supplies of LED lamps

In the paper, the model of the power supply of the LED lamp in the form dedicated for SPICE is proposed. The form of the worked out by the authors' model is presented, and the results of experimental verification of this model for the LED lamp of the type CLA25 are shown. The presented model is elaborated only for the power supply of LED lamps, in which the constant output voltage is stabilized. This model has the form of a subcircuit for SPICE, and it describes the influence of load resistance, amplitude of the input voltage, and the ambient temperature on both the input current and the output voltage. It is confirmed that the worked out model describes correctly both the waveform of the current received from the electroenergy network and the influence of the load current, the ambient temperature, and the supply voltage on the output voltage.     

Ultralow-volume fraction collection from NanoLC columns for mass spectrometric analysis of protein phosphorylation and glycosylation

An ultralow volume fraction collection system referred to as nano fraction analysis chip technology (nanoFACT) is reported. The system collects 25-2500-nL fractions from 75-microm nanoLC columns into pipet tips at a user-defined, timed interval, typically one fraction every 15-120 s. Following collection, the fractions in the tip dry down naturally on their own in such a way as to create a concentrated band at the very end of the interior of the pipet tip. The fractions are then reconstituted directly in the pipet tips in approximately 250 nL of solvent prior to analysis. Because the chromatography and reconstitution solvent are independent, the reconstitution solvent can be selected to maximize ionization efficiency without compromising chromatography. In the infusion analysis of the nanoLC fractions, a low-flow electrospray chip is used which consists of 400 nozzles, each with an inner diameter of 2.5 microm and yielding flow rates of approximately 20 nL/min. Therefore, when reconstituted in 250 nL, each nanoLC fraction can be analyzed for over 10 min. This increase in analysis time allows for signal averaging, resulting in higher data quality, collision energy optimization, slower scanning techniques to be used, such as neutral loss and precursor ion scanning, higher resolution scans on FTMS instruments, and improved peptide quantitation. Furthermore, the nanoLC fractions could be archived in the pipet tips for analysis at a later date. Here, the advantages of nanoFACT are shown for phosphorylation analysis using bovine fetuin and glycosylation analysis using bovine ribonuclease B (RNase B). In the phosphorylation analysis, a comparison between conventional nanoLC and a nanoFACT analysis was performed. An MS/MS spectrum of a triply phosphorylated peptide, 313-HTFSGVApSVEpSpSSGEAFHVGK-333 could only be obtained using nanoFACT, not with nanoLC. Furthermore, spectral quality for the nanoFACT analysis was significantly improved over nanoLC. This was determined by comparing the number of diagnostic ions between the nanoFACT and nanoLC spectra, and it was found that the nanoFACT spectra contained a 19% or greater number of diagnostic ions for nonphosphorylated peptides and 55% or greater for phosphorylated peptides. For the glycosylation analysis, the glycosylation site of RNase B was fully characterized using 100 fmol of tryptic digest on a three-dimensional ion trap mass spectrometer.     

Performance characteristics of an FT MS-based workflow for label-free differential MS analysis of human plasma: standards, reproducibility, targeted feature investigation, and application to a model of controlled myocardial infarction

Proteomics is undergoing a rapid transformation from a qualitative global peptide sequencing discipline into a quantitative, reproducibility-driven practice. Nowhere is this more evident than in the rapidly expanding field of protein biomarker discovery where the general goal is to uncover statistically robust patterns of differential expression between or among subjects/samples representing distinct biological/temporal states. This report presents the analytical characterization of a label-free LC FT-ICR-MS workflow for differential proteomics analysis of human plasma. The key elements discussed include (i) methodologies for performing properly replicated experiments with highly reproducible sample preparation and analysis, including the use of internal standards to quantify variance at different steps in the process, (ii) a new methodology for performing sample re-analysis that uses off-line targeted robotic acquisition of complementary spectral data (e.g. ECD and/or IRMPD) to enhance the identification of differentially expressed peptides/proteins, and (iii) data processing pipelines capable of integrating the automatic statistical analysis of the label-free (LC-) MS signal, together with the intuitive and highly interactive curation and annotation of differential features using the output from standard sequence database search programs. We illustrate the application of the complete sample-to-annotated-differential-peptides (-proteins) workflow by describing the acquisition and analysis of a large multidimensional dataset from patients undergoing a controlled myocardial infarction resulting in an experimental setup in which each patients serve as their own control. Furthermore, we discuss a couple illustrative examples of mid-level proteins observed in this study whose plasma concentrations change consistently within and across patients, in a treatment- and time-dependent fashion.     

Bestimmung von hydraulischen Parametern in Lockergesteinen: Ein Vergleich unterschiedlicher Feldmethoden

In this study the potential of a hydraulic travel-time based inversion approach with analytical solutions for the evaluation of short term pumping tests is assessed. The data base comprises measurements from short-term pumping tests performed in a sand and gravel aquifer using a tomographic measurement array. The evaluation, which is based on an analytical solution, has shown that it is not possible to delimit aquifer zones with different hydraulic properties. The comparison with multi-level slug tests has revealed that the pumping test results are dominated by a zone with a relatively high hydraulic conductivity located close to the bottom of the aquifer. This finding is surprising due to the short pumping time of 200 seconds and due to the hydraulically isolated pumping and observation intervals. The travel-time based inversion, however, allows the reconstruction of vertical and lateral changes in hydraulic diffusivity, between pumping and observation wells, with a high resolution.