High MMP-9 activity characterizes pleural tuberculosis correlating with granuloma formation

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid–alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61–218) pg·mL-1 versus 43 (12–83) pg·mL-1 in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease.

Delamination Fracture Related to Tempering in a High-Strength Low-Alloy Steel

The delamination or splitting of mechanical test specimens of rolled steel plate is a phenomenon that has been studied for many years. In the present study, splitting during fracture of tensile and Charpy V-notch (CVN) test specimens is examined in a high-strength low-alloy plate steel. It is shown that delamination did not occur in test specimens from plate in the as-rolled condition, but was severe in material tempered in the temperature range 500 °C to 650 °C. Minor splitting was seen after heating to 200 °C, 400 °C, and 700 °C. Samples that had been triple quenched and tempered to produce a fine equiaxed grain size also did not exhibit splitting. Microstructural and preferred orientation studies are presented and are discussed as they relate to the splitting phenomenon. It is concluded that the elongated as-rolled grains and grain boundary embrittlement resulting from precipitates (carbides and nitrides) formed during reheating were responsible for the delamination.

High precision C-14 dating of Holocene peat deposits: A comparison of Bayesian calibration and wiggle-matching approaches

The chronologies of five northern European ombrotrophic peat bogs subjected to a large ANIS C-14 dating effort (32-44 dates/site) are presented here. The results of Bayesian calibration (BCal) of dates with a prior assumption of chronological ordering were compared with a Bayesian wiggle-match approach (Bpeat) which assumes constant linear accumulation over sections of the peat profile. Interpolation of BCal age estimates of dense sequences of C-14 dates showed variable patterns of peat accumulation with time, with changes in accumulation occurring at intervals ranging from 20 to 50 cm. Within these intervals, peat accumulation appeared to be relatively linear. Close analysis suggests that some of the inferred variations in accumulation rate were related to the plant macrofossil composition of the peat. The wiggle-matched age-depth models had relatively high chronological uncertainty within intervals of closely spaced 14 C dates, suggesting that the premise of constant linear accumulation over large sections of the peat profile is unrealistic. Age models based on the assumption of linear accumulation over large parts of a peat core (and therefore only effective over millennial timescales), are not compatible with studies examining environmental change during the Holocene, where variability often occurs at decadal to centennial time-scales. Ideally, future wiggle-match age models should be constrained, with boundaries between sections based on the plant macrofossil composition of the peat and physical-chemical parameters such as the degree of decomposition. Strategies for the selection of material for dating should be designed so that there should be enough C-14 dates to accurately reconstruct the peat accumulation rate of each homogeneous stratigraphic unit. (c) 2006 Elsevier Ltd. All rights reserved.

Lack of horizontal gene transfer of methicillin-resitance genetic determinants from PBP2a-positive, coagulase-negative Staphylococci to methicillin-sensitive Staphylococcus aureus using transcutaneous electric nerve stimulation (TENS),

Previous research shows that approximately half of the coagulase-negative staphylococci (CNS) isolated from patients in the intensive care unit (ICU) at Belfast City Hospital were resistant to methicillin. The presence of this relatively high proportion of methicillin-resistance genetic material gives rise to speculation that these organisms may act as potential reservoirs of methicillinresistance genetic material to methicillin-sensitive Staphylococcus aureus (MSSA). Mechanisms of horizontal gene transfer from PBP2a-positive CNS to MSSA, potentially transforming MSSA to MRSA, aided by electroporation-type activities such as transcutaneous electrical nerve stimulation (TENS), should be considered. Methicillin-resistant CNS (MR-CNS) isolates are collected over a two-month period from a variety of clinical specimen types, particularly wound swabs. The species of all isolates are confirmed, as well as their resistance to oxacillin by standard disc diffusion assays. In addition, MSSA isolates are collected over the same period and confirmed as PBP2a-negative. Electroporation experiments are designed to mimic the time/voltage combinations used commonly in the clinical application of TENS. No transformed MRSA were isolated and all viable S. aureus cells remained susceptible to oxacillin and PBP2a-negative. Experiments using MSSA pre-exposed to sublethal concentrations of oxacillin (0.25 µg/mL) showed no evidence of methicillin gene transfer and the generation of an MRSA. The study showed no evidence of horizontal transfer of methicillin resistance genetic material from MR-CNS to MSSA. These data support the belief that TENS and the associated time/voltage combinations used do not increase conjugational transposons or facilitate horizontal gene transfer from MR-CNS to MSSA.

Fasciola hepatica: Histological changes in the reproductive structures of triclabendazole (TCBZ)-sensitive and TCBZ-resistant flukes after treatment in vivo with TCBZ and the related benzimidazole derivative, Compound Alpha

Twenty-four shed-reared lambs were each infected orally with 250 metacercariae of Fasciola hepatica, using either the triclabendazole (TCBZ)-sensitive Cullompton isolate or the TCBZ-resistant Sligo isolate. Twelve weeks after infection the lambs were treated with TCBZ (10 mg/kg) or with the experimental fasciolicide, Compound Alpha (Cpd alpha), a benzimidazole derivative of TCBZ (15 mg/kg). The lambs were euthanised 48,72 and 96 h after TCBZ treatment, or 24, 48 and 72 h after Cpd a treatment, and flukes were collected from the liver and/or gall bladder of each animal. Untreated animals harbouring 12-week infections were euthanised 24 h after administration of anthelmintic to the treatment groups, and the untreated flukes provided control material. A semi-quantitative assessment of the degree of histological change induced by the two drugs after different times of exposure was achieved by scoring the intensity of three well-defined lesions that developed in the testes and uteri of a representative sample of flukes from each lamb. In general, it was found that in those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles), there was progressive loss of cell content due to apparent failure of cell division to keep pace with expulsion of the mature or effete products. Further, actively dividing cell types tended to become individualised, rounded and condensed, characteristic of apoptotic cell death. Protein synthetic activity was apparently inhibited in the Mehlis' secretory cells. In the uterus, where successful formation of shelled eggs represents the culmination of a complex sequence of cytokinetic, cytological and synthetic activity involving the vitelline follicles, the ovary and the Mehlis' gland, histological evidence indicating failure of ovigenesis was evident from 24 h post-treatment onwards. The development of these lesions may be related to the known antitubulin activity of the benzimidazole class of anthelmintics, to the induction of apoptosis in cells where mitosis or meiosis has aborted due to failure of spindle formation, and to drug-induced inhibition of protein synthesis. The semi-quantitative findings indicated that Cpd a is slightly less efficacious than TCBZ itself in causing histological damage to the reproductive structures of TCBZ-sensitive flukes, and that, like TCBZ, it caused no histological damage in flukes of the TCBZ-resistant isolate. This study illustrates the potential utility of histological techniques for conveniently screening representative samples of flukes in field trials designed to validate instances of drug resistance or to test the efficacy of new products against known drug-resistant and drug-susceptible fluke isolates. It also provides reference criteria for drug-induced histopathological changes in fluke reproductive structures which may aid interpretation of TEM findings. (C) 2009 Elsevier B.V. All rights reserved.

High pressures generated by laser driven shocks: applications to planetary physics

High power lasers are a tool that can be used to determine important parameters in the context of Warm Dense Matter, i.e. at the convergence of low-temperature plasma physics and finite-temperature condensed matter physics. Recent results concerning planet inner core materials such as water and iron are presented. We determined the equation of state, temperature and index of refraction of water for pressures up to 7 Mbar. The release state of iron in a LiF window allowed us to investigate the melting temperature near the inner core boundary conditions. Finally, the first application of proton radiography to the study of shocked material is also discussed.

Effect of batch size on mechanical properties of granules in high shear granulation

The flow patterns in a high shear granulator depend on the fill volume. For example, DEM simulations reported by Terashita et al. [1] show that fill volume affects the velocities and kinetic energies of the particles. It also influences the granule size distribution [2]. Here the effects on the properties of the granule are described. The total mass of the granulate material was varied without changing the other variables such as impeller speed, granulation time and liquid to solid ratio. The resulting mechanical properties, such as strength, yield stress and Young's modulus, of the granules were measured. For the materials studied in the current work, increasing the fill factor (batch size) increased the values of these material parameters. This could be explained by the relative increase in the number and intensity of collisions between the particles, when the size of a batch was increased, leading to smaller porosities. (c) 2010 Elsevier B.V. All rights reserved.

Tracing Inspiration in Proverbial Material: From 'The Royal Dictionary' (1699 & 1729) of Abel Boyer to 'The English-Irish Dictionary' (1732) of Begley-McCurtin.

This metalexicographic study examines the relationship between the proverbial material in The English-Irish Dictionary (1732) of Begley and McCurtin, Abel Boyer’s The Royal Dictionary (First edition 1699, second edition 1729), and Nathaniel Bailey’s An Universal Etymological English Dictionary (1721). It will show, for the first time, that both the English macrostructure and microstructure of the proverbial entries in Begley and McCurtin (1732) were reproduced directly from Boyer’s dictionary and, in spite of claims to the contrary, the impact of Bailey’s (1721) dictionary was negligible. Furthermore, empirical data gleaned from a comparative linguistic analysis of the various editions of The Royal Dictionary prior to 1732, will prove that it was the second official edition (1729) that was used as the framework for The English-Irish Dictionary. A quantitative and qualitative analysis of the nature of the proverbial entries will also outline the various translation strategies that were used to compose the Irish material— particularly literal translation—and show that there are extremely high-levels of borrowings from Boyer (1729), both in terms of the English entries under the lemma, and the French entries in the comment.

High-surface thermally stable mesoporous gallium phosphates constituted by nanoparticles as primary building blocks

In constant, search for micro/mesoporous materials, gallium phosphates, have attracted continued interest due to the large pore size reported for some of these solids in comparison with analogous aluminum phosphates. However up to now, the porosity of gallium phosphates collapsed upon template removal or exposure to the ambient moisture. In the present work, we describe high-surface thermally stable mesoporous gallium phosphates synthesized from gallium propoxide and PCl3 and different templating agents such as amines (dipropylamine, piperidine and aminopiperidine) and quaternary ammonium salts (C16H33(CH3)3NBr and C16PyCl). These highly reactive precursors have so far not been used as gallium and phosphate sources for the synthesis of gallophosphates. Conceptually, our present synthetic procedure is based on the fast formation of gallium phosphate nanoparticles via the reaction of gallium propoxide with PCl3 and subsequent construction of the porous material with nanoparticles as building blocks. The organization of the gallophosphate nanoparticles in stable porous structures is effected by the templates. Different experimental procedures varying the molar composition of the sol-gel, pH and the pretreatment of gallium precursor were assayed, most of them leading to satisfactory materials in terms of thermal stability and porosity. In this way, a series of gallium phosphates with surface are above 200 m(2) g(-1), and narrow pore size from 3 to 6 nm and remarkable thermal stability (up to 550 degrees C) have been prepared. In some cases, the structure tends to show some periodicity and regularity as determined by XRD. The remarkable stability has allowed us to test the catalytic activity of gallophosphates for the aerobic oxidation of alkylaromatics with notable good results. Our report reopens the interest for gallophosphates in heterogeneous catalysis. (C) 2010 Elsevier Inc. All rights reserved.

High-velocity features: A ubiquitous property of Type Ia supernovae

Evidence of high-velocity features (HVFs) such as those seen in the near-maximum spectra of some Type Ia supernovae (SNe Ia; e. g., SN 2000cx) has been searched for in the available SN Ia spectra observed earlier than 1 week before B maximum. Recent observational efforts have doubled the number of SNe Ia with very early spectra. Remarkably, all SNe Ia with early data ( seven in our Research Training Network sample and 10 from other programs) show signs of such features, to a greater or lesser degree, in Ca II IR and some also in the Si II lambda 6355 line. HVFs may be interpreted as abundance or density enhancements. Abundance enhancements would imply an outer region dominated by Si and Ca. Density enhancements may result from the sweeping up of circumstellar material (CSM) by the highest velocity SN ejecta. In this scenario, the high incidence of HVFs suggests that a thick disk and/or a high-density companion wind surrounds the exploding white dwarf, as may be the case in single degenerate systems. Large-scale angular fluctuations in the radial density and abundance distribution may also be responsible: this could originate in the explosion and would suggest a deflagration as the more likely explosion mechanism. CSM interaction and surface fluctuations may coexist, possibly leaving different signatures on the spectrum. In some SNe, the HVFs are narrowly confined in velocity, suggesting the ejection of blobs of burned material.

Infection-control strategies for preventing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in nursing homes for older people (Review)

Background: Nursing homes for older people provide an environment likely to promote the acquisition and spread of meticillin-resistant Staphylococcus aureus (MRSA), putting residents at increased risk of colonisation and infection. It is recognised that infection control strategies are important in preventing and controlling MRSA transmission.

Objectives: The objective of this review was to determine the effects of infection control strategies for preventing the transmission of MRSA in nursing homes for older people.

Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2009, Issue 2), the Cochrane Wounds Group Specialised Register (searched May 29th, 2009). We also searched MEDLINE (from 1950 to May Week 4 2009), Ovid EMBASE (1980 to 2009 Week 21), EBSCO CINAHL (1982 to May Week 4 2009), British Nursing Index (1985 to May 2009), DARE (1992 to May 2009), Web of Science (1981 to May 2009), and the Health Technology Assessment (HTA) website (1988 to May 2009). Research in progress was sought through Current Clinical Trials (www.controlled-trials.com), Medical Research Council Research portfolio, and HSRPRoj (current USA projects). SIGLE was also searched in order to identify atypical material which was not accessible through more conventional sources.

Selection criteria: All randomised and controlled clinical trials, controlled before and after studies and interrupted time series studies of infection control interventions in nursing homes for older people were eligible for inclusion.

Data collection and analysis: Two authors independently reviewed the results of the searches.

Main results: Since no studies met the selection criteria, neither a meta-analysis nor a narrative description of studies was possible.

Authors' conclusions: The lack of studies in this field is surprising. Nursing homes for older people provide an environment likely to promote the acquisition and spread of infection, with observational studies repeatedly reporting that being a resident of a nursing home increases the risk of MRSA colonisation. Much of the evidence for recently-issued United Kingdom guidelines for the control and prevention of MRSA in health care facilities was generated in the acute care setting. It may not be possible to transfer such strategies directly to the nursing home environment, which serves as both a healthcare setting and a resident's home. Rigorous studies should be conducted in nursing homes, to test interventions that have been specifically designed for this unique environment.

Influence of aggregate and curing regime on the mechanical properties of ultra-high performance fibre reinforced concrete (UHPFRC)

A new generation of concrete, Ultra-high performance fibre reinforced concrete (UHPFRC) has been developed for its outstanding mechanical performance and shows a very promising future in construction applications. In this paper, several possibilities are examined for reducing the price of producing UHPFRC and for bringing UHPFRC away from solely precast applications and onto the construction site as an in situ material. Recycled glass cullet and two types of local natural sand were examined as replacement materials for the more expensive silica sand normally used to produce UHPFRC. In addition, curing of UHPFRC cubes and prisms at 20 degrees C and 90 degrees C has been investigated to determine differences in both mechanical and ductility.

Challenges of UK/Irish Contractors Regarding Material Management and Logistics in Confined Site Construction

The aim of this paper is to identify the various managerial issues encountered by UK/Irish contractors in the management of materials in confined urban construction sites. Through extensive literature review, detailed interviews, case studies, cognitive mapping, causal loop diagrams, questionnaire survey and documenting severity indices, a comprehensive insight into the materials management concerns within a confined construction site environment is envisaged and portrayed. The leading issues highlighted are: that contractors’ material spatial requirements exceed available space, it is difficult to coordinate the storage of materials in line with the programme, location of the site entrance makes delivery of materials particularly difficult, it is difficult to store materials on-site due to the lack of space, and difficult to coordinate the storage requirements of the various sub-contractors. With the continued development of confined urban centres and the increasing high cost of materials, any marginal savings made on-site would translate into significant monetary savings at project completion. Such savings would give developers a distinct competitive advantage in this challenging economic climate. As on-site management professionals successfully identify, acknowledge and counteract the numerous issues illustrated, the successful management of materials on a confined urban construction site becomes attainable.

Predicting die life from die temperature for high pressure dies casting

The objective of this research was to determine the surface temperature of a high pressure die casting die during casting conditions. This was achieved by instrumentation of an insert which was placed in the shotplate region of the die. This research overcame the challenge of directly measuring the die surface temperature during a HPDC production casting cycle and shows that this is an effective method to determine the die surface temperature during the casting cycle. The instrumentation results gave a peak and minimum temperature of 500 C and 240 C respectively during steady state running conditions with a molten aluminium casting temperature of 660 C. Stress analysis from the steady state measured temperature of the die surface was calculated through a simple FEA model and the resulting stress uctuation was applied to a fatigue equation for the die material, the predicted number of cycles for cracking to start was found to correlate well with observed die damage.

Evaluation of c-FLIP in castrate-resistant prostate cancer antagonizes therapeutic response to androgen receptor-targeted therapy

Purpose: To characterize the importance of cellular Fas-associated death domain (FADD)–like interleukin 1ß-converting enzyme (FLICE) inhibitory protein (c-FLIP), a key regulator of caspase-8 (FLICE)–promoted apoptosis, in modulating the response of prostate cancer cells to androgen receptor (AR)–targeted therapy.

Experimental Design: c-FLIP expression was characterized by immunohistochemical analysis of prostatectomy tissue. The functional importance of c-FLIP to survival and modulating response to bicalutamide was studied by molecular and pharmacologic interventions.

Results: c-FLIP expression was increased in high-grade prostatic intraepithelial neoplasia and prostate cancer tissue relative to normal prostate epithelium (P < 0.001). Maximal c-FLIP expression was detected in castrate-resistant prostate cancer (CRPC; P < 0.001). In vitro, silencing of c-FLIP induced spontaneous apoptosis and increased 22Rv1 and LNCaP cell sensitivity to bicalutamide, determined by flow cytometry, PARP cleavage, and caspase activity assays. The histone deacetylase inhibitors (HDACi), droxinostat and SAHA, also downregulated c-FLIP expression, induced caspase-8- and caspase-3/7–mediated apoptosis, and increased apoptosis in bicalutamide-treated cells. Conversely, the elevated expression of c-FLIP detected in the CRPC cell line VCaP underpinned their insensitivity to bicalutamide and SAHA in vitro. However, knockdown of c-FLIP induced spontaneous apoptosis in VCaP cells, indicating its relevance to cell survival and therapeutic resistance.

Conclusion: c-FLIP reduces the efficacy of AR-targeted therapy and maintains the viability of prostate cancer cells. A combination of HDACi with androgen deprivation therapy may be effective in early-stage disease, using c-FLIP expression as a predictive biomarker of sensitivity. Direct targeting of c-FLIP, however, may be relevant to enhance the response of existing and novel therapeutics in CRPC. Clin Cancer Res; 18(14); 3822–33.