ClgR regulation of chaperone and protease systems is essential for Mycobacterium tuberculosis parasitism of the macrophage

Chaperone and protease systems play essential roles in cellular homeostasis and have vital functions in controlling the abundance of specific cellular proteins involved in processes such as transcription, replication, metabolism and virulence. Bacteria have evolved accurate regulatory systems to control the expression and function of chaperones and potentially destructive proteases. Here, we have used a combination of transcriptomics, proteomics and targeted mutagenesis to reveal that the clp gene regulator (ClgR) of Mycobacterium tuberculosis activates the transcription of at least ten genes, including four that encode protease systems (ClpP1/C, ClpP2/C, PtrB and HtrA-like protease Rv1043c) and three that encode chaperones (Acr2, ClpB and the chaperonin Rv3269). Thus, M. tuberculosis ClgR controls a larger network of protein homeostatic and regulatory systems than ClgR in any other bacterium studied to date. We demonstrate that ClgR-regulated transcriptional activation of these systems is essential for M. tuberculosis to replicate in macrophages. Furthermore, we observe that this defect is manifest early in infection, as M. tuberculosis lacking ClgR is deficient in the ability to control phagosome pH 1 h post-phagocytosis

Effect of physical heterogeneity on the electromigration of nitrate in layered granular porous media

The effect of physical heterogeneity on the electrokinetic (EK) transport of nitrate, an electron acceptor frequently used for anaerobic biodegradation, was investigated experimentally within saturated granular porous media comprising two layers of high and low hydraulic conductivity (K) material. Two hypotheses were tested: firstly, that the presence of layered physical heterogeneity will generate non-uniformities in the electric field; and secondly that this would create non-uniform electromigration of ions resulting in an additional nitrate flux into the lower-K layer. Experiments were conducted in bench-top test cells that contained electrode and sediment chambers. An aqueous nitrate solution (0, 0.1, 1 and 5 g-NO3 L−1) was added at the cathode and the experiments run with an idealised mixture of glass beads and kaolinite, and natural sediment and kaolinite. A constant current (1.6 A m−2) was applied in all experiments. Results showed elevated voltage differences between layers in heterogeneous experiments compared to equivalent homogenous experiments. Furthermore, nitrate concentrations are elevated in the low-K material in heterogeneous compared with homogeneous systems. Using predicted values this is shown to be a function of a transverse flux associated with the voltage difference between layers. The importance of this phenomena at field scale for delivery of an amendment (i.e., electron acceptor, donor or nutrient) by EK for bioremediation is presented in an electron balance model. Overall, this research establishes and quantifies a previously unreported important phenomenon in the electrokinetic transport literature that enhance the application of this technology for bioremediation of contaminated aquifers

Dichromatic polynomials and Potts models summed over rooted maps

We consider the sum of dichromatic polynomials over non-separable rooted planar maps, an interesting special case of which is the enumeration of such maps. We present some known results and derive new ones. The general problem is equivalent to the $q$-state Potts model randomized over such maps. Like the regular ferromagnetic lattice models, it has a first-order transition when $q$ is greater than a critical value $q_c$, but $q_c$ is much larger - about 72 instead of 4.Comment: 29 pages, three figures changes in App D, introduction and acknowledgement

The effect of lipocortin 1 on neutrophil deformability

Lipocortn 1 (Lc1) is an anti-inflammatory protein, which, given systemically, inhibits polymorphonuclear neutrophil (PMN) emigration from the circulation to sites of inflammation; delivery of Lc1 to the inflamed site is ineffective. We have examined the effect of Lc1 on changes in PMN deformability, and observed a consistent improvement in the deformability of unstimulated PMN; N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated cell deformability was unaltered. A Lc1-induced increase in cell deformability may reduce PMN sequestration so contributing to the anti-migratory effects of systemic Lc1 previously demonstrated in vivo

Impact of tumor size and tracer uptake heterogeneity in (18)F-FDG PET and CT non-small cell lung cancer tumor delineation.: 18F-FDG PET and CT tumor delineation in NSCLC

International audienceUNLABELLED: The objectives of this study were to investigate the relationship between CT- and (18)F-FDG PET-based tumor volumes in non-small cell lung cancer (NSCLC) and the impact of tumor size and uptake heterogeneity on various approaches to delineating uptake on PET images. METHODS: Twenty-five NSCLC cancer patients with (18)F-FDG PET/CT were considered. Seventeen underwent surgical resection of their tumor, and the maximum diameter was measured. Two observers manually delineated the tumors on the CT images and the tumor uptake on the corresponding PET images, using a fixed threshold at 50% of the maximum (T(50)), an adaptive threshold methodology, and the fuzzy locally adaptive Bayesian (FLAB) algorithm. Maximum diameters of the delineated volumes were compared with the histopathology reference when available. The volumes of the tumors were compared, and correlations between the anatomic volume and PET uptake heterogeneity and the differences between delineations were investigated. RESULTS: All maximum diameters measured on PET and CT images significantly correlated with the histopathology reference (r > 0.89, P < 0.0001). Significant differences were observed among the approaches: CT delineation resulted in large overestimation (+32% ± 37%), whereas all delineations on PET images resulted in underestimation (from -15% ± 17% for T(50) to -4% ± 8% for FLAB) except manual delineation (+8% ± 17%). Overall, CT volumes were significantly larger than PET volumes (55 ± 74 cm(3) for CT vs. from 18 ± 25 to 47 ± 76 cm(3) for PET). A significant correlation was found between anatomic tumor size and heterogeneity (larger lesions were more heterogeneous). Finally, the more heterogeneous the tumor uptake, the larger was the underestimation of PET volumes by threshold-based techniques. CONCLUSION: Volumes based on CT images were larger than those based on PET images. Tumor size and tracer uptake heterogeneity have an impact on threshold-based methods, which should not be used for the delineation of cases of large heterogeneous NSCLC, as these methods tend to largely underestimate the spatial extent of the functional tumor in such cases. For an accurate delineation of PET volumes in NSCLC, advanced image segmentation algorithms able to deal with tracer uptake heterogeneity should be preferred

SimSearch: A new variant of dynamic programming based on distance series for optimal and near-optimal similarity discovery in biological sequences

http://www.informatik.uni-trier.de/%7Eley/db/conf/iwpacbb/iwpacbb2008.htmlIn this paper, we propose SimSearch, an algorithm implementing a new variant of dynamic programming based on distance series for optimal and near-optimal similarity discovery in biological sequences. The initial phase of SimSearch is devoted to fulfil the binary similarity matrices by signalling the distances between occurrences of the same symbol. The scoring scheme is further applied, when analysed the maximal extension of the pattern. Employing bit parallelism to analyse the global similarity matrix’s upper triangle, the new methodology searches the sequence(s) for all the exact and approximate patterns in regular or reverse order. The algorithm accepts parameterization to work with greater seeds for near-optimal results. Performance tests show significant efficiency improvement over traditional optimal methods based on dynamic programming. Comparing the new algorithm’s efficiency against heuristic based methods, equalizing the required sensitivity, the proposed algorithm remains acceptable.This work has been partially supported by PRODEP

An observation of spin-valve effects in a semiconductor field effect transistor: a novel spintronic device

We present the first spintronic semiconductor field effect transistor. The injector and collector contacts of this device were made from magnetic permalloy thin films with different coercive fields so that they could be magnetized either parallel or antiparallel to each other in different applied magnetic fields. The conducting medium was a two dimensional electron gas (2DEG) formed in an AlSb/InAs quantum well. Data from this device suggest that its resistance is controlled by two different types of spin-valve effect: the first occurring at the ferromagnet-2DEG interfaces; and the second occuring in direct propagation between contacts.Comment: 4 pages, 2 figure

Quality indicators for bladder cancer services : a collaborative review

Context There is a lack of accepted consensus on what should constitute appropriate quality-of-care indicators for bladder cancer. Objective To evaluate the optimal management of bladder cancer and propose quality indicators (QIs). Evidence acquisition A systematic review was performed to identify literature on current optimal management and potential quality indicators for both non–muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer. A panel of experts was convened to select a recommended list of QIs. Evidence synthesis For NMIBC, preoperative QIs include tobacco cessation counselling and appropriate imaging before initial transurethral resection of bladder tumour (TURBT). Intraoperative QIs include administration of antibiotics, proper safe conduct of TURBT using a checklist, and performing restaging TURBT with biopsy of the prostatic urethra in appropriate cases. Postoperative QIs include appropriate receipt of perioperative adjuvant therapy, risk-stratified surveillance, and appropriate decision to change therapy when indicated (eg, unresponsive to bacillus Calmette-Guerin). For MIBC, preoperative QIs include multidisciplinary care, selection for candidates for continent urinary diversion, receipt of neoadjuvant cisplatin-based chemotherapy, time to commencing radical treatment, consideration of trimodal therapy as a bladder-sparing alternative in select patients, preoperative counselling with stoma marking, surgical volume of radical cystectomy, and enhanced recovery after surgery protocols. Intraoperative QIs include adequacy of lymphadenectomy, blood loss, and operative time. Postoperative QIs include prospective standardised monitoring of morbidity and mortality, negative surgical margins for pT2 disease, appropriate surveillance after primary treatment, and adjuvant cisplatin-based chemotherapy in appropriate cases. Participation in clinical trials was highlighted as an important component indicating high quality of care. Conclusions We propose a set of QIs for both NMIBC and MIBC based on established clinical guidelines and the available literature. Measurement of these QIs could aid in improvement and benchmarking of optimal care of bladder cancer. Patient summary After a systematic review of existing guidelines and literature, a panel of experts has recommended a set of quality indicators that can help providers and patients measure and strive towards optimal outcomes for bladder cancer care

Neutron Thermal Cross Sections, Westcott Factors, Resonance Integrals, Maxwellian Averaged Cross Sections and Astrophysical Reaction Rates Calculated from Major Evaluated Data Libraries

We present calculations of neutron thermal cross sections, Westcott factors, resonance integrals, Maxwellian-averaged cross sections and astrophysical reaction rates for 843 ENDF materials using data from the major evaluated nuclear libraries and European activation file. Extensive analysis of newly-evaluated neutron reaction cross sections, neutron covariances, and improvements in data processing techniques motivated us to calculate nuclear industry and neutron physics quantities, produce s-process Maxwellian-averaged cross sections and astrophysical reaction rates, systematically calculate uncertainties, and provide additional insights on currently available neutron-induced reaction data. Nuclear reaction calculations are discussed and new results are presented.Comment: 145 pages, 15 figures, 19 table