bluuebunny/crossref_metadata_2025 huggingface dataset:
Rehabilitating Warranted Assertibility: Moral Inquiry and the Pragmatic Basis of Objectivity
Authors: Frega Roberto
Published: March 2013

This article defends a pragmatic conception of objectivity for the moral domain. I begin by contextualizing pragmatic approaches to objectivity and discuss at some length one of the most interesting proposals in this area,CherylMisak's conception of pragmatic objectivity. My general argument is that in order to defend a pragmatic approach to objectivity, the pragmatic stance should be interpreted in more radical terms than most contemporary proposals do. I suggest in particular that we should disentangle objectivity from truth, and I claim that moral inquiry is in most cases responsive to a normative standard that is closer to warranted assertibility than to truth. Using an argument that relies partly onHuwPrice's account of forms of normative assertion, I will show that a practice‐based account of warranted assertibility does the epistemic work required to defend objectivity while avoiding exposure to the criticisms that are usually addressed against this notion.
Intentionality and Compound Accounts of the Emotions
Authors: Blackman Reid D.
Published: March 2013

Most philosophers of emotion endorse a compound account of the emotions: emotions are wholes made of parts; or, asIprefer to put it, emotions are mental states that supervene on other (mental) states. The goal of this paper is to ascertain how the intentionality of these subvening members relates to the intentionality of the emotions. Towards this end,Iproceed as follows. First,Idiscuss the problems with the accountJustinD'Arms andDanielJacobson offer of the intentionality of the emotions;Iargue their account is fundamentally misguided by virtue of being motivated by a misunderstanding of the nature of propositional attitudes. Second,Iargue againstPeterGoldie's claim that an affective component of an emotion contributes to its intentionality. Third,Ioffer my own compound account of emotions.Iargue (1) emotions are mental states that supervene on other mental states, (2) the mental states that constitute the subvenience base of emotion can have nonconceptual and/or conceptual representational content, and (3) an emotion's intentionality supervenes on (but is often not identical to) the intentionality of only one of its subvening members, specifically, the evaluative representation.
Age refinement of the Messinian salinity crisis onset in the Mediterranean
Authors: Manzi Vinicio , Gennari Rocco , Hilgen Frits , Krijgsman Wout , Lugli Stefano , Roveri Marco , Sierro Francisco J.
Published: March 2013

We propose a revised age calibration of the Messinian salinity crisis onset in the Mediterranean at 5.971 Ma based on the recognition of an extra gypsum cycle in the transitional interval of the Perales section (Sorbas basin, Spain) and the revision of the magnetostratigraphy of the Monticino section (Vena del Gesso basin, Italy). This age re‐calibration allows to state more accurately that: (i) the interval encompassing theMSC‐onset is continuous, thus ruling out any erosional feature or stratigraphic hiatus related to a major sea‐level fall affecting the Mediterranean; (ii) the first gypsum was deposited during the summer insolation peak at 5.969 Ma associated with an eccentricity minimum and roughly coincident with glacial stageTG32; (iii) theMSC‐onset was preconditioned by the tectonically‐driven reduction of the hydrological exchanges with the Atlantic Ocean and finally triggered by glacial conditions in the northern hemisphere and by arid conditions in northern Africa.
Cardiac iron measurement and iron chelation therapy in patients with β thalassaemia major: experience from Taiwan
Authors: Lu M. ‐Y. , Peng S. S. F. , Chang H. ‐H. , Yang Y. ‐L. , Chen C. ‐A. , Jou S. ‐T. , Lin D. ‐T. , Lin K. ‐H.
Published: March 2013

Background

The aims of our study were to evaluate (i) the relationship between cardiac T2* values and cardiac complications in Asian β‐thalassaemia major (TM) patients, and (ii) the association between cardiac T2* values and other parameters currently used to predict cardiac complications as a result of transfusion iron overload.

Methods

We examined the myocardial iron loads of 88 TM patients from Taiwan with cardiac T2* magnetic resonance imaging (MRI) and assessed the correlation between cardiac T2* values and serum ferritin levels, liver iron concentration and left ventricular ejection fraction (LVEF). We also determined the predictive value of these measurements for the development of arrhythmia.

Results and conclusion

In our group of Taiwanese patients, the relative risk for arrhythmia was 10·36 when cardiac T2* values were less than 10 ms (compared with ≥10 ms) and 1·98 when serum ferritin levels increased >2500 ng mL−1 (compared with ≤2500 ng mL−1). Serum ferritin levels correlated with cardiac T2* values in patients with abnormal myocardial iron loads (T2* < 20 ms, r = −0·48, P = 0·004, n = 34), but LVEF (measured by echocardiography) gave no indication of excess myocardial iron deposition (r = −0·07, P = 0·52) or of the risk of developing arrhythmia.
Usefulness of maternal anti‐HPA‐1a antibody quantitation in predicting severity of foetomaternal alloimmune thrombocytopenia
Authors: Sainio S. , Javela K. , Tuimala J. , Koskinen S.
Published: March 2013

Objective

To study the clinical usefulness of maternal anti‐HPA‐1a antibody levels in predicting severe foetomaternal alloimmune thrombocytopenia (FMAIT).

Background

Recent studies using an international anti‐HPA‐1a standard have shown a correlation between maternal antibody levels and neonatal thrombocytopenia. Cut‐off values for identifying high‐risk pregnancies have also been suggested.

Materials

In 1986–2010, HPA‐1a alloimmunisation was confirmed in 84 women with 129 pregnancies. Maternal samples were obtained at delivery and during subsequent pregnancies. Anti‐HPA‐1a was quantified using a MAIPA assay with a detection limit of 0·8 IU mL‐1 (WHO reference serum 03/152). Antibody levels were compared with the severity of neonatal disease in the index and in the subsequent pregnancies.

Results

In the index cases, the correlation between an anti‐HPA‐1a level and neonatal platelet count did not reach statistical significance (n = 77, P = 0·074). However, the platelet counts and antibody levels in cases with cutaneous (n = 45) or intracranial haemorrhage (n = 7) were significantly different from cases with no evidence of bleeding (n = 20). In the subsequent pregnancies, there was a stronger association between the second trimester anti‐HPA‐1a level and the foetal platelet count (n = 16, P = 0·046). The positive predictive value of the maternal antibody level for a foetal platelet count <20 × 109 L‐1 was 90%, but the negative predictive value only 31%.

Conclusion

Although a higher anti‐HPA‐1a level correlated with a more severe neonatal disease, barely detectable antibody levels were also observed in severely affected pregnancies. Cut‐off values with sufficient sensitivity and specificity to identify these foetuses could not be found. A previous obstetric history still remains the most useful predictive parameter for severe FMAIT in clinical practice.
A pilot prospective study of the vascular repair response following red cell transfusion in critically ill patients
Authors: Christou G. , Abou‐Nassar K. , Li Y. , Labonté L. , Tinmouth A. , McArdle T. , Watpool I. , McIntyre L. , Allan D. S.
Published: March 2013

Background

Red blood cell transfusion has been associated with adverse outcomes including infection, delayed recovery and increased mortality in some patient populations. Circulating cells that yield endothelial‐like vascular progenitor cell (VPC) clusters are correlated with vascular repair and recovery after ischaemic injury. The impact of red cell transfusion on VPC clusters and vascular repair remains uncertain.

Study design

We prospectively enrolled patients admitted to intensive care requiring red cell transfusion and subjects at low likelihood of requiring red cell transfusion. Levels of VPC clusters and plasma levels of angiogenic cytokines were compared. A total of 17 patients were recruited and had blood samples collected at time of enrolment and at 24–48 h, 48–72 h and 1 week following transfusion.

Results

We could not discern differences in the number of VPC clusters between transfused patients (n = 6) and non‐transfused subjects (n = 11) at baseline or throughout the study period. VPC cluster levels demonstrated wide variance and were highest at 24‐h post‐enrolment in the entire cohort. Furthermore, levels of all 16 cytokines analysed were not significantly different between transfused and non‐transfused patients and we did not observe a correlation between cytokine concentrations and levels of circulating VPC‐cluster forming cells in the overall study population.

Conclusions

Our data suggest that assessment of vascular repair responses after red blood cell transfusion in critically ill patients is challenging. Although our study did not allow us to discern an influence of red cell transfusion on VPC cluster levels or angiogenic cytokines, new methods evaluating vascular repair mechanisms may be required.
Embryo defective12 encodes the plastid initiation factor 3 and is essential for embryogenesis in maize
Authors: Shen Yun , Li Cuiling , McCarty Donald R. , Meeley Robert , Tan Bao‐Cai
Published: March 2013

Embryo‐specific mutants in maize define a unique class of genetic loci that affect embryogenesis without a significant deleterious impact on endosperm development. Here we report the characterization of an embryo specific12 (emb12) mutant in maize. Embryogenesis in the emb12 mutants is arrested at or before transition stage. The mutant embryo at an early stage exhibits abnormal cell structure with increased vacuoles and dramatically reduced internal membrane organelles. In contrast, the mutant endosperm appears normal in morphology, cell structure, starch, lipid and protein accumulation. The Emb12 locus was cloned by transposon tagging and predicts a protein with a high similarity to prokaryotic translation initiation factor 3 (IF3). EMB12–GFP fusion analysis indicates that EMB12 is localized in plastids. The RNA in situ hybridization and protein immunohistochemical analyses indicate that a high level of Emb12 expression localizes in the embryo proper at early developmental stages and in the embryo axis at later stages. Western analysis indicates that plastid protein synthesis is impaired. These results indicate that Emb12 encodes the plastid IF3 which is essential for embryogenesis but not for endosperm development in maize.
Characteristics of silicon etching by silicon chloride ions
Authors: Ito Tomoko , Karahashi Kazuhiro , Kang Song-Yun , Hamaguchi Satoshi
Published: March 2013

Plasmas generated from halogen-containing gases, such as Cl2 or HBr, have been widely used in gate etching processes for semiconductor chip manufacturing. Such plasmas may contain silicon halide ions formed by the ionization of etching products that enter the plasma. In this study, to illustrate Si etching by such silicon halide ions, the sputtering yield of Si by SiClx+ (with x = 1 or 3) ions has been obtained as a function of the incident ion energy by using a mass-selected ion beam injection system. It has been found that, at sufficiently low energy, the incidence of SiCl+ ions leads to the deposition of Si which may affect profile control in microelectronic device fabrication processes.
Effects of postdeposition annealing on a high-k-last/gate-last integration scheme for 20 nm nMOS and pMOS
Authors: Chen Ying-Tsung , Fu Ssu-I , Lin Chien-Ting , Chiang Wen-Tai , Chang Shoou-Jinn , Lin Mon-Sen , Jenq Jyh-Shyang
Published: March 2013

The authors report the use of postdeposition annealing (PDA) to improve the performance of a high-k (HK)-last/gate-last integration scheme involving the use of a chemical oxide interfacial layer (IL). They find that the chemical oxide IL can form Hf-silicate at the HK/IL interface to provide a larger effective k value and a smaller equivalent oxide thickness. They also find that they can achieve a small gate leakage current density (Jg) and minimal flat-band voltage (Vfb) degradation by PDA in O2 atmosphere. Furthermore, they find that Jg and Vfb can be further improved by optimizing the metal gate stack.
Commissioning of the Varian TrueBeam linear accelerator: A multi‐institutional study
Authors: Glide‐Hurst C. , Bellon M. , Foster R. , Altunbas C. , Speiser M. , Altman M. , Westerly D. , Wen N. , Zhao B. , Miften M. , Chetty I. J. , Solberg T.
Published: March 2013

Purpose:

Latest generation linear accelerators (linacs), i.e., TrueBeam (Varian Medical Systems, Palo Alto, CA) and its stereotactic counterpart, TrueBeam STx, have several unique features, including high‐dose‐rate flattening‐filter‐free (FFF) photon modes, reengineered electron modes with new scattering foil geometries, updated imaging hardware/software, and a novel control system. An evaluation of five TrueBeam linacs at three different institutions has been performed and this work reports on the commissioning experience.

Methods:

Acceptance and commissioning data were analyzed for five TrueBeam linacs equipped with 120 leaf (5 mm width) MLCs at three different institutions. Dosimetric data and mechanical parameters were compared. These included measurements of photon beam profiles (6X, 6XFFF, 10X, 10XFFF, 15X), photon and electron percent depth dose (PDD) curves (6, 9, 12 MeV), relative photon output factors (Scp), electron cone factors, mechanical isocenter accuracy, MLC transmission, and dosimetric leaf gap (DLG). End‐to‐end testing and IMRT commissioning were also conducted.

Results:

Gantry/collimator isocentricity measurements were similar (0.27–0.28 mm), with overall couch/gantry/collimator values of 0.46–0.68 mm across the three institutions. Dosimetric data showed good agreement between machines. The average MLC DLGs for 6, 10, and 15 MV photons were 1.33 ± 0.23, 1.57 ± 0.24, and 1.61 ± 0.26 mm, respectively. 6XFFF and 10XFFF modes had average DLGs of 1.16 ± 0.22 and 1.44 ± 0.30 mm, respectively. MLC transmission showed minimal variation across the three institutions, with the standard deviation <0.2% for all linacs. Photon and electron PDDs were comparable for all energies. 6, 10, and 15 MV photon beam quality, %dd(10)x varied less than 0.3% for all linacs. Output factors (Scp) and electron cone factors agreed within 0.27%, on average; largest variations were observed for small field sizes (1.2% coefficient of variation, 10 MV, 2 × 2 cm2) and small cone sizes (<1% coefficient of variation, 6 × 6 cm2 cone), respectively.

Conclusions:

Overall, excellent agreement was observed in TrueBeam commissioning data. This set of multi‐institutional data can provide comparison data to others embarking on TrueBeam commissioning, ultimately improving the safety and quality of beam commissioning.
Dependency of image quality on system configuration parameters in a stationary digital breast tomosynthesis system
Authors: Tucker Andrew W. , Lu Jianping , Zhou Otto
Published: March 2013

Purpose:

In principle, a stationary digital breast tomosynthesis (s‐DBT) system has better image quality when compared to continuous motion DBT systems due to zero motion blur of the source. The authors have developed a s‐DBT system by using a linear carbon nanotube x‐ray source array. The purpose of the current study was to quantitatively evaluate the performance of the s‐DBT system; and investigate the dependence of imaging quality on the system configuration parameters.

Methods:

Physical phantoms were used to assess the image quality of each configuration including inplane resolution as measured by the modulation transfer function (MTF), inplane contrast as measured by the signal difference to noise ratio (SdNR), and depth resolution as measured by the z‐axis artifact spread function. Five parameters were varied to create five groups of configurations: (1) total angular span; (2) total number of projection images; (3) distribution of exposure (mAs) across the projection images; (4) entrance dose; (5) detector pixel size.

Results:

It was found that the z‐axis depth resolution increased with the total angular span but was insensitive to the number of projection images, mAs distribution, entrance dose, and detector pixel size. The SdNR was not affected by the angular span or the number of projection images. A decrease in SdNR was observed when the mAs was not evenly distributed across the projection images. As expected, the SdNR increased with entrance dose and when larger pixel sizes were used. For a given detector pixel size, the inplane resolution was found to be insensitive to the total angular span, number of projection images, mAs distribution, and entrance dose. A 25% increase in the MTF was observed when the detector was operating in full resolution mode (70μm pixel size) compared to 2 × 2 binned mode (140 μm pixel size).

Conclusions:

The results suggest that the optimal imaging configuration for a s‐DBT system is a large angular span, an intermittent number of projection views, and a uniform mAs distribution over all views. With the detector operating at full resolution, a stationary DBT system can achieve an inplane resolution of 5.1 cycles per mm, which is significantly better than continuous motion DBT systems.
Monte Carlo investigation of I‐125 interseed attenuation for standard and thinner seeds in prostate brachytherapy with phantom validation using a MOSFET
Authors: Mason J. , Al‐Qaisieh B. , Bownes P. , Henry A. , Thwaites D.
Published: March 2013

Purpose:

In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG‐43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively.

Methods:

A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight‐seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT‐based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models.

Results:

In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%–18.3% (6711) and 7.8%–16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG‐43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%).

Conclusions:

ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG‐43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.
Automated x‐ray/light field congruence using the LINAC EPID panel
Authors: Polak Wojciech , O'Doherty Jim , Jones Matt
Published: March 2013

Purpose:

X‐ray/light field alignment is a test described in many guidelines for the routine quality control of clinical linear accelerators (LINAC). Currently, the gold standard method for measuring alignment is through utilization of radiographic film. However, many modern LINACs are equipped with an electronic portal imaging device (EPID) that may be used to perform this test and thus subsequently reducing overall cost, processing, and analysis time, removing operator dependency and the requirement to sustain the departmental film processor.

Methods:

This work describes a novel method of utilizing the EPID together with a custom inhouse designed jig and automatic image processing software allowing measurement of the light field size, x‐ray field size, and congruence between them. The authors present results of testing the method for aS1000 and aS500 Varian EPID detectors for six LINACs at a range of energies (6, 10, and 15 MV) in comparison with the results obtained from the use of radiographic film.

Results:

Reproducibility of the software in fully automatic operation under a range of operating conditions for a single image showed a congruence of 0.01 cm with a coefficient of variation of 0. Slight variation in congruence repeatability was noted through semiautomatic processing by four independent operators due to manual marking of positions on the jig. Testing of the methodology using the automatic method shows a high precision of 0.02 mm compared to a maximum of 0.06 mm determined by film processing. Intraindividual examination of operator measurements of congruence was shown to vary as much as 0.75 mm. Similar congruence measurements of 0.02 mm were also determined for a lower resolution EPID (aS500 model), after rescaling of the image to the aS1000 image size.

Conclusions:

The designed methodology was proven to be time efficient, cost effective, and at least as accurate as using the gold standard radiographic film. Additionally, congruence testing can be easily performed for all four cardinal gantry angles which can be difficult when using radiographic film. Therefore, the authors propose it can be used as an alternative to the radiographic film method allowing decommissioning of the film processor.
Using Fisher information to quantify uncertainty in environmental parameters estimated from correlated ambient noise
Authors: Walker Shane C. , Yardim Caglar , Thode Aaron , Arias-Castro Ery
Published: March 2013

Efforts to characterize environmental parameters from ambient noise must contend with uncertainty introduced by stochastic fluctuations of the noise itself. This Letter calculates the Fisher information and Cramer-Rao bound of an unbiased correlated ambient noise parameter estimate. As an illustration, lower bounds on the error covariance of medium speed and attenuation parameters are obtained for a two-dimensional isotropic ambient noise scenario. The results demonstrate that an optimal sensor separation exists for obtaining the minimum error and the predictions are validated using simulated parameter inversions. The influences of record length, bandwidth, signal-to-noise, and spatial resolution are discussed.
Characteristics of Extended-Spectrum β-Lactamase- and Carbapenemase-Producing Enterobacteriaceae Isolates from Rivers and Lakes in Switzerland
Authors: Zurfluh Katrin , Hächler Herbert , Nüesch-Inderbinen Magdalena , Stephan Roger
Published: March 2013

One of the currently most relevant resistance mechanisms in
Enterobacteriaceae
is the production of enzymes that lead to modern expanded-spectrum cephalosporin and even carbapenem resistance, mainly extended-spectrum β-lactamases (ESBLs) and carbapenemases. A worrisome aspect is the spread of ESBL and carbapenemase producers into the environment. The aim of the present study was to assess the occurrence of ESBL- and carbapenemase-producing
Enterobacteriaceae
and to further characterize ESBL- and carbapenemase-producing
Enterobacteriaceae
in rivers and lakes in Switzerland. ESBL-producing
Enterobacteriaceae
were detected in 21 (36.2%) of the 58 bodies of water sampled. One river sample tested positive for a carbapenemase-producing
Klebsiella pneumoniae
subsp.
pneumoniae
strain. Seventy-four individual strains expressing an ESBL phenotype were isolated. Species identification revealed 60
Escherichia coli
strains, seven
Klebsiella pneumoniae
subsp.
pneumoniae
strains, five
Raoultella planticola
strains, one
Enterobacter cloacae
strain, and one
Enterobacter amnigenus
strain. Three strains were identified as SHV-12 ESBL producers, and 71 strains carried genes encoding CTX-M ESBLs. Of the 71 strains with CTX-M ESBL genes, 8 isolates expressed CTX-M-1, three produced CTX-M-3, 46 produced CTX-M-15, three produced CTX-M-55, one produced CTX-M-79, six produced CTX-M-14, and four produced CTX-M-27. Three of the four CTX-M-27 producers belonged to the multiresistant pandemic sequence type
E. coli
B2:ST131 that is strongly associated with potentially severe infections in humans and animals.
Autotrophic Growth of Bacterial and Archaeal Ammonia Oxidizers in Freshwater Sediment Microcosms Incubated at Different Temperatures
Authors: Wu Yucheng , Ke Xiubin , Hernández Marcela , Wang Baozhan , Dumont Marc G. , Jia Zhongjun , Conrad Ralf
Published: March 2013

Both bacteria and archaea potentially contribute to ammonia oxidation, but their roles in freshwater sediments are still poorly understood. Seasonal differences in the relative activities of these groups might exist, since cultivated archaeal ammonia oxidizers have higher temperature optima than their bacterial counterparts. In this study, sediment collected from eutrophic freshwater Lake Taihu (China) was incubated at different temperatures (4°C, 15°C, 25°C, and 37°C) for up to 8 weeks. We examined the active bacterial and archaeal ammonia oxidizers in these sediment microcosms by using combined stable isotope probing (SIP) and molecular community analysis. The results showed that accumulation of nitrate in microcosms correlated negatively with temperature, although ammonium depletion was the same, which might have been related to enhanced activity of other nitrogen transformation processes. Incubation at different temperatures significantly changed the microbial community composition, as revealed by 454 pyrosequencing targeting bacterial 16S rRNA genes. After 8 weeks of incubation, [
13
C]bicarbonate labeling of bacterial
amoA
genes, which encode the ammonia monooxygenase subunit A, and an observed increase in copy numbers indicated the activity of ammonia-oxidizing bacteria in all microcosms.
Nitrosomonas
sp. strain Is79A3 and
Nitrosomonas communis
lineages dominated the heavy fraction of CsCl gradients at low and high temperatures, respectively, indicating a niche differentiation of active bacterial ammonia oxidizers along the temperature gradient. The
13
C labeling of ammonia-oxidizing archaea in microcosms incubated at 4 to 25°C was minor. In contrast, significant
13
C labeling of
Nitrososphaera
-like archaea and changes in the abundance and composition of archaeal
amoA
genes were observed at 37°C, implicating autotrophic growth of ammonia-oxidizing archaea under warmer conditions.
Positive Feedback Regulation of
stgR
Expression for Secondary Metabolism in Streptomyces coelicolor
Authors: Mao Xu-Ming , Sun Zhi-Hao , Liang Bi-Rong , Wang Zhi-Bin , Feng Wei-Hong , Huang Fang-Liang , Li Yong-Quan
Published: March 2013

LysR-type transcriptional regulators (LTTRs) compose a large family and are responsible for various physiological functions in bacteria, while little is understood about their regulatory mechanism on secondary metabolism in
Streptomyces
. Here we reported that StgR, a typical LTTR in
Streptomyces coelicolor
, was a negative regulator of undecylprodigiosin (Red) and γ-actinorhodin (Act) production in the early developmental phase of secondary metabolism by suppressing the expression of two pathway-specific regulator genes,
redD
and
actII-orf4
, respectively. Meanwhile,
stgR
expression was downregulated during secondary metabolism to remove its repressive effects on antibiotic production. Moreover,
stgR
expression was positively autoregulated by direct binding of StgR to its own promoter (
stgRp
), and the binding site adjacent to translation start codon was determined by a DNase I footprinting assay. Furthermore, the StgR-
stgRp
interaction could be destroyed by the antibiotic γ-actinorhodin produced from
S. coelicolor
. Thus, our results suggested a positive feedback regulatory mechanism of
stgR
expression and antibiotic production for the rapid and irreversible development of secondary metabolism in
Streptomyces
.
6S-1 RNA Function Leads to a Delay in Sporulation in Bacillus subtilis
Authors: Cavanagh Amy T. , Wassarman Karen M.
Published: March 2013

We have discovered that 6S-1 RNA (encoded by
bsrA
) is important for appropriate timing of sporulation in
Bacillus subtilis
in that cells lacking 6S-1 RNA sporulate earlier than wild-type cells. The time to generate a mature spore once the decision to sporulate has been made is unaffected by 6S-1 RNA, and, therefore, we propose that it is the timing of onset of sporulation that is altered. Interestingly, the presence of cells lacking 6S-1 RNA in coculture leads to all cell types exhibiting an early-sporulation phenotype. We propose that cells lacking 6S-1 RNA modify their environment in a manner that promotes early sporulation. In support of this model, resuspension of wild-type cells in conditioned medium from Δ
bsrA
cultures also resulted in early sporulation. Use of
Escherichia coli
growth as a reporter of the nutritional status of conditioned media suggested that
B. subtilis
cells lacking 6S-1 RNA reduce the nutrient content of their environment earlier than wild-type cells. Several pathways known to impact the timing of sporulation, such as the
skf
- and
sdp
-dependent cannibalism pathways, were eliminated as potential targets of 6S-1 RNA-mediated changes, suggesting that 6S-1 RNA activity defines a novel mechanism for altering the timing of onset of sporulation. In addition, 6S-2 RNA does not influence the timing of sporulation, providing further evidence of the independent influences of these two related RNAs on cell physiology.
The Major Outer Sheath Protein (Msp) of Treponema denticola Has a Bipartite Domain Architecture and Exists as Periplasmic and Outer Membrane-Spanning Conformers
Authors: Anand Arvind , Luthra Amit , Edmond Maxwell E. , Ledoyt Morgan , Caimano Melissa J. , Radolf Justin D.
Published: March 2013

The major outer sheath protein (Msp) is a primary virulence determinant in
Treponema denticola
, as well as the parental ortholog for the
Treponema pallidum
repeat (Tpr) family in the syphilis spirochete. The Conserved Domain Database (CDD) server revealed that Msp contains two conserved domains, major outer sheath protein
N
(MOSP
N
) and MOSP
C
, spanning residues 77 to 286 and 332 to 543, respectively, within the N- and C-terminal regions of the protein. Circular dichroism (CD) spectroscopy, Triton X-114 (TX-114) phase partitioning, and liposome incorporation demonstrated that full-length, recombinant Msp (Msp
Fl
) and a recombinant protein containing MOSP
C
, but not MOSP
N
, form amphiphilic, β-sheet-rich structures with channel-forming activity. Immunofluorescence analysis of intact
T. denticola
revealed that only MOSP
C
contains surface-exposed epitopes. Data obtained using proteinase K accessibility, TX-114 phase partitioning, and cell fractionation revealed that Msp exists as distinct OM-integrated and periplasmic trimers. Msp
Fl
folded in Tris buffer contained slightly less β-sheet structure than detergent-folded Msp
Fl
; both forms, however, partitioned into the TX-114 detergent-enriched phase. CDD analysis of the nine Tpr paralogs predicted to be outer membrane proteins (OMPs) revealed that seven have an Msp-like bipartite structure; phylogenetic analysis revealed that the MOSP
N
and MOSP
C
domains of Msp are most closely related to those of TprK. Based upon our collective results, we propose a model whereby a newly exported, partially folded intermediate can be either processed for OM insertion by the β-barrel assembly machinery (BAM) or remain periplasmic, ultimately forming a stable, water-soluble trimer. Extrapolated to
T. pallidum
, our model enables us to explain how individual Tprs can localize to either the periplasmic (e.g., TprK) or OM (e.g., TprC) compartments.
The Stringent Response Controls Catalases in Pseudomonas aeruginosa and Is Required for Hydrogen Peroxide and Antibiotic Tolerance
Authors: Khakimova Malika , Ahlgren Heather G. , Harrison Joe J. , English Ann M. , Nguyen Dao
Published: March 2013

Pseudomonas aeruginosa
, a human opportunistic pathogen, possesses a number of antioxidant defense enzymes under the control of multiple regulatory systems. We recently reported that inactivation of the
P. aeruginosa
stringent response (SR), a starvation stress response controlled by the alarmone (p)ppGpp, caused impaired antioxidant defenses and antibiotic tolerance. Since catalases are key antioxidant enzymes in
P. aeruginosa
, we compared the levels of H
2
O
2
susceptibility and catalase activity in
P. aeruginosa
wild-type and Δ
relA
Δ
spoT
(ΔSR) mutant cells. We found that the SR was required for optimal catalase activity and mediated H
2
O
2
tolerance during both planktonic and biofilm growth. Upon amino acid starvation, induction of the SR upregulated catalase activity. Full expression of
katA
and
katB
also required the SR, and this regulation occurred through both RpoS-independent and RpoS-dependent mechanisms. Furthermore, overexpression of
katA
was sufficient to restore H
2
O
2
tolerance and to partially rescue the antibiotic tolerance of ΔSR cells. All together, these results suggest that the SR regulates catalases and that this is an important mechanism in protecting nutrient-starved and biofilm bacteria from H
2
O
2
- and antibiotic-mediated killing.
Differential Detergent Extraction of Mycobacterium marinum Cell Envelope Proteins Identifies an Extensively Modified Threonine-Rich Outer Membrane Protein with Channel Activity
Authors: van der Woude Aniek D. , Mahendran Kozhinjampara R. , Ummels Roy , Piersma Sander R. , Pham Thang V. , Jiménez Connie R. , de Punder Karin , van der Wel Nicole N. , Winterhalter Mathias , Luirink Joen , Bitter Wilbert , Houben Edith N. G.
Published: March 2013

A striking characteristic of mycobacteria is the presence of an unusual outer membrane which forms a thick permeability barrier and provides resistance to many antibiotics. Although specialized proteins must reside in this layer, only few mycolate outer membrane (MOM) proteins have been identified to date. Their discovery is complicated by difficulties in obtaining good separation of mycobacterial inner and outer membranes. During our efforts to identify novel mycobacterial outer membrane proteins (MOMPs), we discovered that we can enrich for MOMPs using differential solubilization of mycobacterial cell envelopes. Subsequently, these different fractions were analyzed by nano liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS). This proteomic analysis confirmed that our marker proteins for inner membrane and MOM were found in their expected fractions and revealed a few interesting candidate MOMPs. A number of these putative MOMPs were further analyzed for their expression and localization in the cell envelope. One identified MOMP, MMAR_0617 of
Mycobacterium marinum
, was purified and demonstrated to form a large oligomeric complex. Importantly, this protein showed a clear single-channel conductance of 0.8 ± 0.1 ns upon reconstitution into artificial planar lipid bilayers. The most surprising feature of MMAR_0617 is a long C-terminal threonine-rich domain with extensive modifications. In summary, we have identified a novel mycobacterial outer membrane porin with unusual properties.
Use of Acupuncture for Pain Management in An Academic Korean Medicine Hospital: A Retrospective Review of Electronic Medical Records
Authors: Kim Kun Hyung , Kim Yu Ri , Noh Seung Hee , Kang Kyung Won , Kim Jae Kyu , Yang Gi Young , Lee Byung Ryul
Published: March 2013

Objective

This study aimed to identify the descriptive characteristics of patients with pain conditions who visited an academic medical centre for traditional Korean medicine (TKM).

Methods

This work was a retrospective review of the electronic medical records of patients who received at least one session of acupuncture for pain management from March 2010 to February 2012 in the Korean medical hospital of Pusan National University. Demographic characteristics and data on patient conditions, treatment interventions received and costs associated with acupuncture treatments were analysed.

Results

We identified a total of 2167 patients, including 2105 outpatients and 237 inpatients. The mean age (SD) of the patients was 52.0 (15.3) years, and approximately two-thirds of the patients were women (64.0%). The average number of acupuncture treatment sessions was 8.0 (6.6 for outpatients and 14.5 for inpatients). The most treated conditions were low back pain (30.5%), neck pain (23.9%) and shoulder pain (17.5%). Interventions included needle acupuncture with manual (52.6%) or electrical (47.4%) stimulation, herbal medicine (44.2%), cupping (21.2%) and moxibustion (3.5%). Over one-third of outpatients (33.5%) received at least six sessions of acupuncture. The median total cost of each outpatient and inpatient care per person was 169 604 and 1 001 707 Korean Won (approximately £98 and £577), respectively.

Conclusions

Acupuncture was primarily used for the treatment of low back, neck and shoulder pain with a wide range of related interventions at an academic medical centre for traditional Korean medicine. These data reflect real clinical practice and should inform the design of future prospective clinical research of acupuncture.
Effect of Acupuncture on Target Tissue Distribution of Schisandra lignans
Authors: Lu Tu-Lin , Wu Xiao-Yan , Song Yu , Chen Hao , Xu Bin , Zhou Yuan , Huang Zhi-Jun , Sun Yong , Mao Chun-Qin
Published: March 2013

Background

Recently, the combination of acupuncture and Chinese medicine as a practical strategy to treat diseases is receiving considerable attention worldwide as they are usually found to exhibit intriguing therapeutic effectiveness. The current study aimed to study the adjunct effect of acupuncture on target tissue distribution of schisandra lignans when acupuncture is combined with Schisandra chinensis.

Methods

A simple and reliable high performance liquid chromatography-electrospray tandem-mass spectrometry (HPLC-ESI-MS) method for simultaneous analysis of three bioactive lignans (schisandrin, deoxyschisandrin and schisandrin B) in rat tissues was established. Using this analytical method we evaluated whether acupuncture had a synergistic effect on the tissue distribution of schisandra lignans.

Results

Tissue concentrations of the three lignans in the group receiving acupuncture were significantly higher than those in the schisandra only group, suggesting that acupuncture may potently increase tissue concentrations of schisandra lignans. The highest concentrations of the three lignans occurred in the liver compared with other tissues, and tissue concentrations in the heart, spleen, lungs and kidneys were increased by 315%, 203%, 250% and 224%, respectively. In addition, retention times of the lignans in tissues were prolonged for a relative long time.

Conclusions

Our date indicate that the combined use of acupuncture and Schisandra chinensis could produce a synergistic effect which could play a beneficial role on promoting the tissue distribution of lignans. This has supported our initial hypothesis. The HPLC-MS method showed good sensitivity in quantifying the three schisandra lignans in different tissues.
Pneumocystis pneumonia in a non-HIV patient on chronic corticosteroid therapy: a question of prophylaxis
Authors: Plakke Michael J , Jalota Leena , Lloyd Benjamin J
Published: March 2013

A man in his late 50s with a history of membranoproliferative glomerulonephritis presented with fever and mild dyspnoea. He was HIV-negative and had been on corticosteroids as immunosuppression for 6 months prior to tapering them off 1 week before presentation. He was not taking prophylaxis forPneumocystis jiroveciipneumonia. After unsuccessful treatment for community-acquired pneumonia, his condition worsened and he required intubation and mechanical ventilation. Full respiratory workup including bronchoscopy revealedP jiroveciias a source for the patient's infection. He was treated successfully with a 21-day course of trimethoprim-sulfamethoxazole  and eventually weaned off the ventilator. He has had no complications to date. In our review of this case and the existing literature, we believe that proper utilisation of prophylaxis for pneumocystis pneumonia may have prevented our patient's transfer to intensive care unit. In our article, we discuss this issue and explore current evidence for prophylaxis.
A dangerous cough
Authors: Chitnis Abhishek Rajeev
Published: March 2013

Patient X is a 48-year-old retired potteries worker who presented to his general practitioner (GP) with a non-productive cough, which had lasted over 1 month, and it was a television advert that he had seen that prompted him to visit his doctor. A cough is the most common presenting complaint for patients when they visit their GP and when considering differential diagnoses it is important to look at a patient's medical, drug and social history. It would have been easy for the GP to dismiss the cough as an exacerbation of the patient's asthma based on his medical history, but on further questioning into the patient's social history an emergency chest x-ray was ordered, which later revealed a bronchial carcinoma. This case highlights the importance of the media in healthcare advertising and describes how a fairly innocent presentation can later turn out to be a more sinister pathology.
Diversities in presentations of extrapulmonary tuberculosis
Authors: Neelakantan Shiba , Nair Preeti P , Emmanuel Roby V , Agrawal Kavita
Published: March 2013

The incidence of extrapulmonary tuberculosis (EPTB) has been increasing worldwide over the last few years. Tuberculous lymphadenitis is the most common form of the disease and is reported to occur in 25–60% of all EPTB cases. It is commonly seen in the cervical lymph nodes, but may also be in the larynx, pharynx, parotid and rarely, in the sinuses and petrous bone. The posterior triangle, supraclavicular and jugular nodes are most frequently affected. They are usually unilateral, although diffuse adenopathy may occur. TB involving cervical lymph nodes represents 50% of extrapulmonary TB. A series of six cases of tuberculous lymphadenitis with varying clinical features is documented here to alert one of its prevalence in developing countries.
Haemophagocytic syndrome with disseminated intravascular coagulation associated with tuberculosis
Authors: Cherif Eya , Bel Feki Nabil , Ben Hassine Lamia , Khalfallah Narjess
Published: March 2013

Haemophagocytic syndrome (HPS) is a clinical entity that combines non-specific clinical and biological features. The diagnosis is usually confirmed by a bone marrow examination. HPS may be primary or secondary to a malignancy or to an infectious or autoimmune disease. Early aggressive survey of the aetiology and optimal treatment of the underlying disease improve the outcome of life-threatening HPS. Infection-associated HPS occurs predominantly in immunocompromised patients and is usually fatal. Leading trigger agents are viruses, especially the Epstein-Barr virus  and cytomegalovirus. Mycobacterial infections associated with HPS are rare but should be considered in those patients where there is associated fever of unknown origin. We present a case of disseminated tuberculosis-associated HPS.
The interactions of ethical notions and moral values of immediate stakeholders of immunisation services in two Indian states: a qualitative study
Authors: Varghese Joe , Raman Kutty V , Ramanathan Mala
Published: March 2013

Objectives

This study examines the existing norms regarding immunisation within the communities and the ethical notions that govern the actions of different health professionals and their collective synergistic or conflicting effects on the governance of the programme.

Design

We used descriptive and analytical qualitative methods as it suited the research question.

Setting

The data were collected from areas under 16 primary health centres in Kerala and Tamil Nadu identified through a three-step sampling process.

Participants

This involved in-depth interviews with stakeholders including providers, beneficiaries and other stakeholders, focus group discussions with mothers of under-five children and participant and non-participant observations of vaccination-related activities.

Results

Unlike most other ethical analyses that look at the ethics of vaccination policies, the interactions of normative principles and notions are analysed in this article. Moral obligation of parents towards their children, beneficence of healthcare providers and the utilitarian aspirations of the state are the key normative principles involved. Our analysis points to the interplay of both synergy and conflict in ethical notions and moral values in the context of immunisation services. Paternalistic interventions like special immunisation campaigns against polio and Japanese encephalitis are a case in point: they generate conflict at the normative level and create mistrust.

Conclusions

Analysis of vaccination policies and programmes needs to go beyond factors that assess monetary benefits or herd immunity. Understanding the interactions of normative notions that shape the social organisation of the providers and the users of vaccination is important in creating a sustainable environment for the programme.
Semen quality and reproductive hormones in Faroese men: a cross-sectional population-based study of 481 men
Authors: Halling Jónrit , Petersen Maria Skaalum , Jørgensen Niels , Jensen Tina Kold , Grandjean Philippe , Weihe Pál
Published: March 2013

Objectives

To determine semen quality and reproductive hormone levels in young Faroese men.

Design

Descriptive cross-sectional study of Faroese men compared with Danish men.

Setting

Faroese one-centre study.

Participants

481 men born from 1981 to 1987 and investigated from 2007 to 2010.

Outcome measures

Sperm concentration, semen volume, total sperm count, sperm motility, sperm morphology and reproductive hormone levels.

Results

Sperm concentrations for the Faroese men were lower than for the Danish men (crude median 40 vs 48 mill/ml, p<0.0005). Semen volume was higher, and thus the total sperm counts did not differ (159 vs 151 mill, p=0.2). Motility and morphology did not differ between the Faroese and Danes. The inhibin B/follicle-stimulating hormone ratios for the Faroese men were lower than for the Danes (64 vs 76, p=0.001). Similarly, lower total testosterone/luteinising hormone (LH) ratio (4.6 vs 6.0, p<0.0005) and lower calculated free-testosterone/LH ratio (94 vs 134, p<0.0005) were detected for the Faroese men.

Conclusions

Semen quality among the Faroese men is at the same low level as reported for Danish men, and the reproductive hormone levels furthermore indicated a lower Leydig cell capacity for testosterone production. The influence of environmental exposure and genetic factors on semen quality has to be studied further.