Multi-scale mechanistic modelling of the host defence in invasive aspergillosis reveals leucocyte activation and iron acquisition as drivers of infection outcome

Aspergillus species are ubiquitous environmental moulds, with spores inhaled daily by most humans. Immunocompromised hosts can develop an invasive infection resulting in high mortality. There is, therefore, a pressing need for host-centric therapeutics for this infection. To address it, we created a multi-scale computational model of the infection, focused on its interaction with the innate immune system and iron, a critical nutrient for the pathogen. The model, parameterized using published data, was found to recapitulate a wide range of biological features and was experimentally validated in vivo. Conidial swelling was identified as critical in fungal strains with high growth, whereas the siderophore secretion rate seems to be an essential prerequisite for the establishment of the infection in low-growth strains. In immunocompetent hosts, high growth, high swelling probability and impaired leucocyte activation lead to a high conidial germination rate. Similarly, in neutropenic hosts, high fungal growth was achieved through synergy between high growth rate, high swelling probability, slow leucocyte activation and high siderophore secretion. In summary, the model reveals a small set of parameters related to fungal growth, iron acquisition and leucocyte activation as critical determinants of the fate of the infection.     

An examination of land use change due to irrigated agriculture in north‐eastern Jordan using geoinformatics

The Jordanian government has encouraged irrigated agriculture since the early 1990s by providing low cost loans to drill private wells. The impacts of this practice on land use change were examined within a small (362 km²) area of the Jordanian Badia using Geoinformatics. Aerial photographs, SPOT and Landsat TM imageries were used, in a GIS environment, to map and examine changes in the farming patterns since 1990. Field surveys and questionnaires were used to ground truth the remotely sensed data. The results indicate that the cultivated area has increased from just 28.5 ha in 1990 to over 1000 ha in 2000 and that the number of farms has increased from 2 to 32 over the same time period. Furthermore, farm locations are moved annually restricted by the position of the well and land availability; this also causes land use change.     

Fluorimetric Nerve Gas Sensing Based on Pyrene Imines Incorporated into Films and Sub‐Micrometer Fibers

The chemical sensing of nerve gas agents has become an increasingly important goal due to the 1995 terrorist attack in a Tokyo subway as well as national security concerns in regard to world affairs. Chemical detection needs to be sensitive and selective while being facile, portable, and timely. In this paper, a sensing approach using a pyrene imine molecule is presented that is fluorimetric in response. The detection of a chloro‐Sarin surrogate is measured at 5 ppmv in less than 1 second and is highly selective towards halogenated organophosphates. The pyrene imine molecule is incorporated into polystyrene films as well as micrometer and sub‐micrometer fibers. Using both a direct drawing approach and electrospinning, micrometer and nanofibers can be easily manufactured. Applications for functional sensing micrometer and nanofibers are envisioned for optical devices and photonics in addition to solution and airflow sensing devices.     

Evolution of the arthropod prophenoloxidase/hexamerin protein family

PURPOSE: Because intraperitoneal (i.p.) therapy may provide a therapeutic advantage and because hyperthermia enhances carboplatin (CBDCA) cytotoxicity, we evaluated the feasibility, toxicity, and pharmacokinetics of CBDCA given via continuous hyperthermic peritoneal perfusion (CHPP) in patients with small-volume residual ovarian cancer. Patients and METHODS: Six patients underwent optimal cytoreductive procedures (residual disease < or =5 mm) as initial treatment of stages II and III epithelial ovarian adenocarcinoma. All patients received a 90-min CHPP at a CBDCA dose of 800-1200 mg/m2, with the perfusate being recirculated rapidly from a reservoir through a heat exchanger, resulting in i.p. temperatures of 41-43 degrees C. Plasma, perfusate, and urine samples were collected and platinum was quantified by flameless atomic absorption spectrophotometry. RESULTS: At no time did any patient's core temperature exceed 40 degrees C. Peak perfusate platinum concentrations were 8- to 15-fold higher than peak ultrafilterable plasma concentrations. The permeability-area product was extremely high and variable (14-90 ml/min), resulting in a regional advantage of 1.9-5.3. The percentage of the dose absorbed ranged widely from 27% to 77%. Dose-limiting hematologic toxicity was observed at a dose of 1200 mg/m2 and this was associated with a CBDCA AUC in plasma of 11 mg min ml(-1). CONCLUSION: CHPP with CBDCA was safely given to three patients at a dose of 800 mg/m2, and dose-limiting hematologic toxicities observed at 1200 mg/m2, correlated with the plasma CBDCA exposure established when lower doses of CBDCA are given systemically. The pharmacokinetic data are consistent with the expected effect of vigorous mixing on the exposed peritoneal surface area. Variable drug absorption and clearance make the prediction of systemic exposure highly uncertain. These findings may have important implications for novel therapies given i.p.     

输电线路自适应无通道保护(一)故障分析与保护原理

在故障分析的基础上，提出了利用单端故障信息的输电线路全线速动保护原理和动作判据。保护原理由互为补充的两种动作模式－－延时动作模式和瞬时动作模式构成。延时模式利用线路对端开关动作信息加速本端保护动作；瞬时模式根据阻抗继电器Ⅱ段动作定值瞬时动作跳闸，再利用重合闸并根据开关动作后的信息纠正错误动作的结果。保护动作判据由4个独立的故障序分量的比值构成，仿真实验证实了所提保护原理和动作判据的正确性。     

The sizes of peptides generated from protein by mammalian 26 and 20 S proteasomes. Implications for understanding the degradative mechanism and antigen presentation

Knowledge about the sizes of peptides generated by proteasomes during protein degradation is essential to fully understand their degradative mechanisms and the subsequent steps in protein turnover and generation of major histocompatibility complex class I antigenic peptides. We demonstrate here that 26 S and activated 20 S proteasomes from rabbit muscle degrade denatured, nonubiquitinated proteins in a highly processive fashion but generate different patterns of peptides (despite their containing identical proteolytic sites). With both enzymes, products range in length from 3 to 22 residues, and their abundance decreases with increasing length according to a log-normal distribution. Less than 15% of the products are the length of class I presented peptides (8 or 9 residues), and two-thirds are too short to function in antigen presentation. Surprisingly, these mammalian proteasomes, which contain two "chymotryptic," two "tryptic," and two "post-acidic" active sites, generate peptides with a similar size distribution as do archaeal 20 S proteasomes, which have 14 identical sites. Furthermore, inactivation of the "tryptic" sites altered the peptides produced without significantly affecting their size distribution. Therefore, this distribution is not determined by the number, specificity, or arrangement of the active sites (as proposed by the "molecular ruler" model); instead, we propose that proteolysis continues until products are small enough to diffuse out of the proteasomes.     

Aciduric, pH-Elevating Bacillus which Cause Noneffervescent Spoilage of Underprocessed Tomatoes

In the preliminary phase of this study, a selective isolation medium was developed. Using the new medium, 24 strains of Bacillus Spp. that elevate tomato juice pH were isolated from garden soil or natural vegetative materials. Two jars of home-canned, water-bathed tomatoes contained sporeformers which produced noneffervescent spoilage. All strains were morphologically and physiologically different from 2 flat-sour strains of B. coagulans and B. licheniformis strains, but similar to a previous isolate from home-canned, spoiled green beans that elevated pH. The new medium may have future applications in isolation and enumeration of other acidurics including yeast-like microorganisms.