bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the (f)utility of measuring the lead equivalence of protective garments
Authors: Jones A. Kyle , Wagner Louis K. 
Published: May 2013

Purpose:Protective garments incorporating lead (Pb) or other moderate to high atomic number elements are a necessary radiation protection tool. However, as lead has been replaced by other elements, verifying manufacturers’ claims regarding the lead equivalence of such garments has become nearly impossible, and current standards only require measurement of attenuation or lead equivalence at a single beam quality. A garment may provide a high degree of protection at the specified beam quality, but underperform at others. The authors sought to measure the lead equivalence of several protective garments and propose a better method for quantifying the protective value of garments.Methods:The authors measured the penetration of primary and scattered radiation through lead sheets and three protective garments of nominal 0.5 mm Pb equivalence, one lead and two lead‐free. Penetration was measured using beams of nominal 60, 80, 100, and 120 kVp. Primary penetration through protective garments at 70 kVp was also measured. A lead‐lined enclosure was constructed for measuring scatter penetration, as instruments must be protected from stray radiation when measuring low‐level penetration of scattered radiation. Using polynomial least‐squares fits to the measured data of penetration through lead sheets, the authors determined the lead equivalence of the protective garments across a range of beam qualities.Results:The lead garment was 0.5 mm Pb equivalent across all beam qualities evaluated. While the maximum lead equivalence of the lead‐free garments did occur at the manufacturer‐specified beam quality, neither garment was 0.5 mm Pb equivalent at the specified beam quality. The lead equivalence of the lead‐free garments was a strong function of beam quality and nature of the radiation, i.e., primary or scattered. The lead equivalence of the lead‐free garments in primary beams ranged from 0.40 to 0.47 mm Pb equivalent and in scattered beams ranged from 0.37 to 0.46 mm Pb equivalent. The penetration through one lead‐free garment at 60 kVp was 478% higher than the penetration through the lead garment. The authors have also provided linear fits of radiation penetration through lead as a function of half‐value layer. It is likely that assessment of protective value can be performed using primary beams matched to the spectra of scattered beams. The authors propose the diagnostic radiation index of protection (DRIP), a weighted sum of the percentage of radiation penetration across a range of beam qualities, as a more robust method for specifying the protective value of garments.Conclusions:The protective value of garments from both primary and scattered radiation is a strong function of beam quality. Assessment of the protective value should be performed across a range of beam qualities. Methods for performing such assessment must be developed and must specify beam qualities, measurement geometry, and the appropriate weighting across the beam quality range for different applications.
Quantitative analysis of geometric information from an end‐to‐end examination of IMRT and VMAT using the optimal selection method
Authors: Tachibana Hidenobu , Takahashi Ryo 
Published: May 2013

Purpose:Gamma index, distance‐to‐agreement, and dose difference (DD) are commonly used to evaluate planar dose distributions. In this evaluation, the agreement between calculated and measured dose distributions can be susceptible to steep dose gradients along another axis perpendicular to the evaluation plane. Visual registration of the measured dose distribution may be performed to achieve better agreement, although doing so might lose geometric information related to beam targeting in an end‐to‐end test of intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). The optimal selection (OS) method was developed to take into consideration a dose distribution in three‐dimensions, and also to quantitatively analyze geometric information along with better agreement.Methods:The OS method was composed of two steps. These steps were based on two algorithms, the gamma index and DD, to (1) find the best‐matched plane, which is parallel to the planar measured dose distribution and is reconstructed by a volumetric dose distribution calculated by a treatment planning system; and (2) to get shifts and rotation along with better agreement between the calculated and measured dose distribution, compared with the planar dose distribution from the test. The OS method computes shifts and rotation against a user‐defined coregistered location for the measured dose distribution. Thirteen prostate IMRT plans (two planes per plan for a total of 26 planes) were analyzed retrospectively to compare the pass ratios of DD and gamma index evaluations with and without the OS method. The computed shifts and rotations were evaluated.Results:Compared with the method without OS, the average pass ratios of DD and gamma index with the OS method increased by 8.2% and 5.7%, respectively, in the dose region from 30% to 100%. A particular result from one of the planes showed an increase of 43.5% and 32.5% in the pass ratios of DD and gamma, respectively, with the OS method in the same dose region. The shifts in the x‐, y‐, z‐axes and rotation, which were computed using the OS method, were 0.5 ± 0.6, 0.3 ± 0.5, 1.0 ± 1.1 mm, and 0.3 ± 0.3°, respectively. In terms of the comparatively large difference between the z‐shift and the x‐ and y‐shifts, an additional geometric test was performed. A systematic error of 0.7 mm in the z‐axis was found at the location of the film placed in the phantom that we used.Conclusions:The OS method improved the quality of the end‐to‐end test of IMRT and VMAT plans by providing additional information regarding shifts and rotation, which were calculated and found to be in better agreement.
Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in Acinetobacter baumannii
Authors: Napier Brooke A. , Burd Eileen M. , Satola Sarah W. , Cagle Stephanie M. , Ray Susan M. , McGann Patrick , Pohl Jan , Lesho Emil P. , Weiss David S. 
Published: May 2013

ABSTRACT

The alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This problem is compounded by the absence of new antibiotics close to regulatory approval.
Acinetobacter baumannii
is a human pathogen that causes infections primarily in patients in intensive care units (ICUs) and is highly antibiotic resistant. Colistin is one of the last-line antibiotics for treating
A. baumannii
infections; however, colistin-resistant strains are becoming increasingly common. This cationic antibiotic attacks negatively charged bacterial membranes in a manner similar to that seen with cationic antimicrobials of the innate immune system. We therefore set out to determine if the increasing use of colistin, and emergence of colistin-resistant strains, is concomitant with the generation of cross-resistance to host cationic antimicrobials. We found that there is indeed a positive correlation between resistance to colistin and resistance to the host antimicrobials LL-37 and lysozyme among clinical isolates. Importantly, isolates obtained before and after treatment of individual patients demonstrated that colistin use correlated with increased resistance to cationic host antimicrobials. These data reveal the overlooked risk of inducing cross-resistance to host antimicrobials when treating patients with colistin as a last-line antibiotic.

IMPORTANCE
Increased use of the cationic antibiotic colistin to treat multidrug-resistant
Acinetobacter baumannii
has led to the development of colistin-resistant strains. Here we report that treatment of patients with colistin can induce not only increased resistance to colistin but also resistance to host cationic antimicrobials. This worrisome finding likely represents an example of a broader trend observed in other bacteria against which colistin is used therapeutically such as
Pseudomonas aeruginosa
and
Klebsiella pneumoniae
. Furthermore, these data suggest that the possible future use of an array of cationic antimicrobial peptides in development as therapeutics may have unintended negative consequences, eventually leading to the generation of hypervirulent strains that are resistant to innate host defenses. The potential for the induction of cross-resistance to innate immune antimicrobials should be considered during the development of new therapeutics.
Experimental Verification of the Identity of Variant-Specific Surface Proteins in Giardia lamblia Trophozoites
Authors: Li Wei , Saraiya Ashesh A. , Wang Ching C. 
Published: May 2013

ABSTRACT

The cell membrane of a
Giardia lamblia
trophozoite is covered with a single species of variant-specific surface protein (VSP) that is replaced by another VSP every 6 to 13 generations of cell growth, possibly for an evasion of host immunity. Experimentally, only six VSP species have been verified to localize to the cell membrane thus far. By assuming that VSP contains multiple CXXC motifs, 219
vsp
genes were annotated in GiardiaDB of the WB isolate. By further assuming that VSP possesses both CXXC motifs and a CRGKA tail at the C terminus, Adam et al. (BMC Genomics 11:424, 2010) identified a total of 303 potential
vsp
genes in
Giardia
WB. The discrepancies between these two assumed VSP identities have caused some confusion. Here, we used experimental approaches to further verify what is required of the structures of a VSP to localize to the surface of cell membrane. The data led to the following conclusions. (i) The C-terminal CRGKA sequence is not essential for localizing VSPs to the cell membrane. (ii) A “motif 1” of 45 residues, consisting of two CXXCs separated by 12 to 15 amino acid residues, located close to the C terminus and a hydrophobic “motif 2” of 38 residues at the C terminus are both essential and sufficient for localizing the protein to the cell membrane. (ii) An N-terminal sequence upstream from motif 1 is not required for targeting VSPs to the cell membrane. By these criteria, we are able to identify 73 open reading frames as the putative
vsp
genes in
Giardia
.

IMPORTANCE
The intestinal pathogen
Giardia lamblia
expresses only one variant-specific surface protein (VSP) on the cell membrane surface at a given time, but it changes spontaneously every 6 to 13 generations of growth, presumably for evading the host immunity. Only 6 VSPs have been empirically shown to localize to the cell membrane surface thus far. Here, we used mutations of VSPs and methods of identifying their locations in
Giardia
cells and found that a “motif 1” of 45 residues, consisting of two CXXCs separated by 12 to 15 amino acid residues, located close to the C terminus and a hydrophobic “motif 2” of 38 residues at the C terminus are the only essential and sufficient structural requirements for localizing a protein to the cell membrane. By these criteria, 73 genes are identified in the
Giardia
WB strain genome database as the putative repertoire of VSPs.
Acyltransferases in Bacteria
Authors: Röttig Annika , Steinbüchel Alexander 
Published: May 2013

SUMMARY
Long-chain-length hydrophobic acyl residues play a vital role in a multitude of essential biological structures and processes. They build the inner hydrophobic layers of biological membranes, are converted to intracellular storage compounds, and are used to modify protein properties or function as membrane anchors, to name only a few functions. Acyl thioesters are transferred by acyltransferases or transacylases to a variety of different substrates or are polymerized to lipophilic storage compounds. Lipases represent another important enzyme class dealing with fatty acyl chains; however, they cannot be regarded as acyltransferases in the strict sense. This review provides a detailed survey of the wide spectrum of bacterial acyltransferases and compares different enzyme families in regard to their catalytic mechanisms. On the basis of their studied or assumed mechanisms, most of the acyl-transferring enzymes can be divided into two groups. The majority of enzymes discussed in this review employ a conserved acyltransferase motif with an invariant histidine residue, followed by an acidic amino acid residue, and their catalytic mechanism is characterized by a noncovalent transition state. In contrast to that, lipases rely on completely different mechanism which employs a catalytic triad and functions via the formation of covalent intermediates. This is, for example, similar to the mechanism which has been suggested for polyester synthases. Consequently, although the presented enzyme types neither share homology nor have a common three-dimensional structure, and although they deal with greatly varying molecule structures, this variety is not reflected in their mechanisms, all of which rely on a catalytically active histidine residue.
Role of Pore-Forming Toxins in Bacterial Infectious Diseases
Authors: Los Ferdinand C. O. , Randis Tara M. , Aroian Raffi V. , Ratner Adam J. 
Published: May 2013

SUMMARYPore-forming toxins (PFTs) are the most common bacterial cytotoxic proteins and are required for virulence in a large number of important pathogens, includingStreptococcus pneumoniae, group A and B streptococci,Staphylococcus aureus,Escherichia coli, andMycobacterium tuberculosis. PFTs generally disrupt host cell membranes, but they can have additional effects independent of pore formation. Substantial effort has been devoted to understanding the molecular mechanisms underlying the functions of certain model PFTs. Likewise, specific host pathways mediating survival and immune responses in the face of toxin-mediated cellular damage have been delineated. However, less is known about the overall functions of PFTs during infectionin vivo. This review focuses on common themes in the area of PFT biology, with an emphasis on studies addressing the roles of PFTs inin vivoandex vivomodels of colonization or infection. Common functions of PFTs include disruption of epithelial barrier function and evasion of host immune responses, which contribute to bacterial growth and spreading. The widespread nature of PFTs make this group of toxins an attractive target for the development of new virulence-targeted therapies that may have broad activity against human pathogens.
The Unexpected Roles of Eukaryotic Translation Elongation Factors in RNA Virus Replication and Pathogenesis
Authors: Li Dongsheng , Wei Ting , Abbott Catherine M. , Harrich David 
Published: May 2013

SUMMARY
The prokaryotic translation elongation factors were identified as essential cofactors for RNA-dependent RNA polymerase activity of the bacteriophage Qβ more than 40 years ago. A growing body of evidence now shows that eukaryotic translation elongation factors (eEFs), predominantly eEF1A, acting in partially characterized complexes sometimes involving additional eEFs, facilitate virus replication. The functions of eEF1A as a protein chaperone and an RNA- and actin-binding protein enable its “moonlighting” roles as a virus replication cofactor. A diverse group of viruses, from human immunodeficiency type 1 and West Nile virus to tomato bushy stunt virus, have adapted to use eEFs as cofactors for viral transcription, translation, assembly, and pathogenesis. Here we review the mechanisms used by viral pathogens to usurp these abundant cellular proteins for their replication.
Toxin Plasmids of Clostridium perfringens
Authors: Li Jihong , Adams Vicki , Bannam Trudi L. , Miyamoto Kazuaki , Garcia Jorge P. , Uzal Francisco A. , Rood Julian I. , McClane Bruce A. 
Published: May 2013

SUMMARYIn both humans and animals,Clostridium perfringensis an important cause of histotoxic infections and diseases originating in the intestines, such as enteritis and enterotoxemia. The virulence of this Gram-positive, anaerobic bacterium is heavily dependent upon its prolific toxin-producing ability. Many of the ∼16 toxins produced byC. perfringensare encoded by large plasmids that range in size from ∼45 kb to ∼140 kb. These plasmid-encoded toxins are often closely associated with mobile elements. AC. perfringensstrain can carry up to three different toxin plasmids, with a single plasmid carrying up to three distinct toxin genes. Molecular Koch's postulate analyses have established the importance of several plasmid-encoded toxins whenC. perfringensdisease strains cause enteritis or enterotoxemias. Many toxin plasmids are closely related, suggesting a common evolutionary origin. In particular, most toxin plasmids and some antibiotic resistance plasmids ofC. perfringensshare an ∼35-kb region containing a Tn916-related conjugation locus namedtcp(transfer of clostridial plasmids). Thistcplocus can mediate highly efficient conjugative transfer of these toxin or resistance plasmids. For example, conjugative transfer of a toxin plasmid from an infecting strain toC. perfringensnormal intestinal flora strains may help to amplify and prolong an infection. Therefore, the presence of toxin genes on conjugative plasmids, particularly in association with insertion sequences that may mobilize these toxin genes, likely providesC. perfringenswith considerable virulence plasticity and adaptability when it causes diseases originating in the gastrointestinal tract.
Sampling technique is important for optimal isolation of pharyngeal gonorrhoea
Authors: Mitchell M , Rane V , Fairley C K , Whiley D M , Bradshaw C S , Bissessor M , Chen M Y 
Published: May 2013

BackgroundCulture is insensitive for the detection of pharyngeal gonorrhoea but isolation is pivotal to antimicrobial resistance surveillance. The aim of this study was to ascertain whether recommendations provided to clinicians (doctors and nurses) on pharyngeal swabbing technique could improve gonorrhoea detection rates and to determine which aspects of swabbing technique are important for optimal isolation.MethodsThis study was undertaken at the Melbourne Sexual Health Centre, Australia. Detection rates among clinicians for pharyngeal gonorrhoea were compared before (June 2006–May 2009) and after (June 2009–June 2012) recommendations on swabbing technique were provided. Associations between detection rates and reported swabbing technique obtained via a clinician questionnaire were examined.ResultsThe overall yield from testing before and after provision of the recommendations among 28 clinicians was 1.6% (134/8586) and 1.8% (264/15 046) respectively (p=0.17). Significantly higher detection rates were seen following the recommendations among clinicians who reported a change in their swabbing technique in response to the recommendations (2.1% vs 1.5%; p=0.004), swabbing a larger surface area (2.0% vs 1.5%; p=0.02), applying more swab pressure (2.5% vs 1.5%; p<0.001) and a change in the anatomical sites they swabbed (2.2% vs 1.5%; p=0.002). The predominant change in sites swabbed was an increase in swabbing of the oropharynx: from a median of 0% to 80% of the time.ConclusionsMore thorough swabbing improves the isolation of pharyngeal gonorrhoea using culture. Clinicians should receive training to ensure swabbing is performed with sufficient pressure and that it covers an adequate area that includes the oropharynx.
Lineage Relationship of Gleason Patterns in Gleason Score 7 Prostate Cancer
Authors: Kovtun Irina V. , Cheville John C. , Murphy Stephen J. , Johnson Sarah H. , Zarei Shabnam , Kosari Farhad , Sukov William R , Karnes R. Jeffrey , Vasmatzis George 
Published: May 2013

Abstract
Gleason score 7 (GS7) prostate cancer [tumors with both Gleason patterns 3 (GP3) and 4 (GP4)] portends a significantly more aggressive tumor than Gleason score 6 (GS6). It is, therefore, critical to understand the molecular relationship of adjacent GP3 and GP4 tumor cell populations and relate molecular abnormalities to disease progression. To decipher molecular relatedness, we used laser capture microdissection (LCM) and whole-genome amplification (WGA) to separately collect and amplify DNA from adjacent GP3 and GP4 cell populations from 14 cases of GS7 prostate cancer. We then carried out massively parallel mate-pair next generation sequencing (NGS) to examine the landscape of large chromosomal alterations. We identified four to 115 DNA breakpoints in GP3 and 17 to 480 in GP4. Our findings indicate that while GP3 and GP4 from the same tumor each possess unique breakpoints, they also share identical ones, indicating a common origin. Approximately 300 chromosomal breakpoints were localized to the regions affected in at least two tumors, whereas more than 3,000 were unique within the set of 14 tumors. TMPRSS2–ERG was the most recurrent rearrangement present in eight cases, in both GP3 and GP4. PTEN rearrangements were found in five of eight TMPRSS2–ERG fusion–positive cases in both GP3 and GP4. Hierarchical clustering analysis revealed that GP3 has greater breakpoint similarity to its partner GP4 compared with GP3 from different patients. We show evidence that LCM, WGA, and NGS of adjacent tumor regions provide an important tool in deciphering lineage relationships and discovering chromosomal alterations associated with tumor progression. Cancer Res; 73(11); 3275–84. ©2013 AACR.
Visualizing Inhibition of Nucleosome Mobility and Transcription by Cisplatin–DNA Interstrand Crosslinks in Live Mammalian Cells
Authors: Zhu Guangyu , Song Lina , Lippard Stephen J. 
Published: May 2013

Abstract
Cisplatin is a widely used anticancer drug that acts by binding DNA and causing the formation of intrastrand and interstrand (ICL) crosslinks, but the precise downstream effects of the latter damage are not well understood. In this study, we investigated the influence of cisplatin ICLs on synthetic nucleosomes that were platinated in a site-specific manner in vitro and on gene transcription in live mammalian cells. Nucleosome core particles that we constructed contained site-specific cisplatin 5′-d(G*pC)/5′-d(G*pC) ICLs, where the asterisk denotes the platinated nucleoside, to examine the influence of platinum lesions on the dynamic behavior of nucleosomes in solution. A cisplatin ICL, but not a 1,2-d(GpG) crosslink, significantly inhibited ATP-independent histone octamer-DNA sliding. We also used a novel linearization-recircularization strategy described here to synthesize mammalian expression vectors containing site-specific cisplatin ICLs. Plasmid vectors were tested in live mammalian cells to study the transcription inhibition effects of cisplatin ICLs in the context of two different repair backgrounds. Cisplatin ICLs inhibit transcription as effectively as 1,2-d(GpG) crosslinks. We determined that nucleotide excision repair plays a key role in the removal of cisplatin ICLs, acting in a replication-independent fashion. We also found that loss of mismatch repair function dramatically attenuates the transcription inhibition effects by cisplatin ICLs but not 1,2-d(GpG) intrastrand crosslinks. Our results revealed the unique properties of cisplatin ICLs on nucleosome mobility and on transcription, and they defined how these adducts act in a manner completely different from that used for cisplatin 1,2-d(GpG) crosslinks. These new findings provide direct support for a role of ICLs in the pharmacologic activities of cisplatin, despite the lower frequency of their formation. Cancer Res; 73(14); 4451–60. ©2013 AACR.