bluuebunny/crossref_metadata_2025_split huggingface dataset:
ORIGINAL ARTICLE: Use of 3D imaging and awareness of GEC‐ESTRO recommendations for cervix cancer brachytherapy throughout Australia and New Zealand
Authors: Van Dyk S , Byram D , Bernshaw D 
Published: August 2010

AbstractIntroduction:  A 2005 survey of practices indicated limited use of three‐dimensional (3D) imaging modalities and planning methods in cervix cancer brachytherapy in Australia and New Zealand. However, advancing technologies and published recommendations are influencing change. This survey aims to identify both changes in practice and awareness and uptake of Groupe European de Curietherapie of the European Society for Therapeutic Radiology and Oncology (GEC‐ESTRO) recommendations.Methods:  A survey was emailed to all radiotherapy departments with brachytherapy facilities. Twenty departments practise brachytherapy for cancer of the cervix. The survey consisted of five questions enquiring about use and type of 3D imaging; rate of reimaging and replanning; and contouring, prescribing and reporting practices.Results:  A 100% response rate was obtained. Sixty‐five per cent of departments use 3D CT imaging to plan brachytherapy insertions. Thirty per cent of departments use two‐dimensional (2D) x‐rays. Four departments (20%) use a combination of imaging modalities including CT, ultrasound and MRI. Sixty‐five per cent of departments reimage and replan for each insertion. Four departments (20%) contour, prescribe dose and report treatment according to GEC‐ESTRO recommendations.Conclusions:  There has been a marked increase in the use of 3D imaging and awareness of GEC‐ESTRO recommendations. Implementation and reporting of image‐based gynaecological brachytherapy is strongly dependent on local resources and infrastructure.
POINT OF VIEW: Strategies to successfully publish your first manuscript
Authors: Veness M 
Published: August 2010

SummaryApplying published evidence is fundamental to the practice of medicine. However, the steps needed to undertake scientific research and generate a manuscript of publishable quality are often overwhelming for junior doctors. Undertaking research and publishing these findings are complementary. Clinicians often present research at college or scientific meetings as oral or poster presentations. Yet despite this, most research is not subsequently submitted for peer review publication in a scientific journal. Reasons put forward for research not being published include lack of time, ongoing study, difficulties with co‐authors and a negative study. A lack of experience in the actual process of writing and publishing is also likely to be a contributing factor. The steps required in writing a successful manuscript are multiple and clinicians often lack awareness of the specific formatting requirements for submission to a scientific journal such as JMIRO. The aim of this article is to provide information for clinicians inexperienced in writing and submitting a manuscript with the intent of achieving a publication. It is not meant to be a step‐by‐step recipe in doing this but a guide as to what is required.
Identification and Characterization of Four Azole-Resistant
erg3
Mutants of
Candida albicans
Authors: Martel Claire M. , Parker Josie E. , Bader Oliver , Weig Michael , Gross Uwe , Warrilow Andrew G. S. , Rolley Nicola , Kelly Diane E. , Kelly Steven L. 
Published: August 2010

ABSTRACT

Sterol analysis identified four
Candida albicans erg3
mutants in which ergosta 7,22-dienol, indicative of perturbations in sterol Δ
5,6
-desaturase (Erg3p) activity, comprised >5% of the total sterol fraction. The
erg3
mutants (CA12, CA488, CA490, and CA1008) were all resistant to fluconazole, voriconazole, itraconazole, ketoconazole, and clotrimazole under standard CLSI assay conditions (MIC values, ≥256, 16, 16, 8, and 1 μg ml
−1
, respectively). Importantly, CA12 and CA1008 retained an azole-resistant phenotype even when assayed in the presence of FK506, a multidrug efflux inhibitor. Conversely, CA488, CA490, and three comparator isolates (CA6, CA14, and CA177, in which ergosterol comprised >80% of the total sterol fraction and ergosta 7,22-dienol was undetectable) all displayed azole-sensitive phenotypes under efflux-inhibited assay conditions. Owing to their ergosterol content, CA6, CA14, and CA177 were highly sensitive to amphotericin B (MIC values, <0.25 μg ml
−1
); CA1008, in which ergosterol comprised <2% of the total sterol fraction, was less sensitive (MIC, 1 μg ml
−1
). CA1008 harbored multiple amino acid substitutions in Erg3p but only a single conserved polymorphism (E266D) in sterol 14α-demethylase (Erg11p). CA12 harbored one substitution (W332R) in Erg3p and no residue changes in Erg11p. CA488 and CA490 were found to harbor multiple residue changes in both Erg3p and Erg11p. The results suggest that missense mutations in
ERG3
might arise in
C. albicans
more frequently than currently supposed and that the clinical significance of
erg3
mutants, including those in which additional mechanisms also contribute to resistance, should not be discounted.
Complementation of a
Saccharomyces cerevisiae
ERG11/CYP51 (Sterol 14α-Demethylase) Doxycycline-Regulated Mutant and Screening of the Azole Sensitivity of
Aspergillus fumigatus
Isoenzymes CYP51A and CYP51B
Authors: Martel Claire M. , Parker Josie E. , Warrilow Andrew G. S. , Rolley Nicola J. , Kelly Steven L. , Kelly Diane E. 
Published: August 2010

ABSTRACT

Aspergillus fumigatus
sterol 14α-demethylase isoenzymes CYP51A and CYP51B were heterologously expressed in a
Saccharomyces cerevisiae
mutant (YUG37-
erg11
), wherein native ERG11/CYP51 expression is controlled using a doxycycline-regulatable promoter. When cultured in the presence of doxycycline, recombinant YUG37-p
cyp51A
and YUG37-p
cyp51B
yeasts were able to synthesize ergosterol and grow; a control strain harboring reverse-oriented
cyp51A
could not. YUG37-p
cyp51A
and YUG37-p
cyp51B
constructs showed identical sensitivity to itraconazole, posaconazole, clotrimazole, and voriconazole. Conversely, YUG37-p
cyp51A
withstood 16-fold-higher concentrations of fluconazole than YUG37-p
cyp51B
(8 and 0.5 μg ml
−1
, respectively).
Genotypic Characterization of UL23 Thymidine Kinase and UL30 DNA Polymerase of Clinical Isolates of Herpes Simplex Virus: Natural Polymorphism and Mutations Associated with Resistance to Antivirals
Authors: Burrel Sonia , Deback Claire , Agut Henri , Boutolleau David 
Published: August 2010

ABSTRACTThe molecular mechanisms of herpes simplex virus (HSV) resistance to antiviral drugs interfering with viral DNA synthesis reported so far rely on the presence of mutations within UL23 (thymidine kinase [TK]) and UL30 (DNA polymerase) genes. The interpretation of genotypic antiviral resistance assay results requires the clear distinction between resistance mutations and natural interstrain sequence variations. The objectives of this work were to describe extensively the natural polymorphism of UL23 TK and UL30 DNA polymerase among HSV-1 and HSV-2 strains and the amino acid changes potentially associated with HSV resistance to antivirals. The sequence analysis of the full-length UL23 and UL30 genes was performed. Ninety-four drug-sensitive clinical isolates (43 HSV-1 and 51 HSV-2) and 3 laboratory strains (KOS, gHSV-2, and MS2) were studied for natural polymorphism, and 25 clinical isolates exhibiting phenotypic traits of resistance to antivirals were analyzed for drug resistance mutations. Our results showed that TK and DNA polymerase are highly conserved among HSV strains, with a weaker variability for HSV-2 strains. This study provided a precise map of the natural polymorphism of both viral enzymes among HSV-1 and HSV-2 isolates, with the identification of 15 and 51 polymorphisms never previously described for TK and DNA polymerase, respectively, which will facilitate the interpretation of genotypic antiviral-resistant testing. Moreover, the genotypic characterization of 25 drug-resistant HSV isolates revealed 8 new amino acid changes located in TK and potentially accounting for acyclovir (ACV) resistance.
Mechanisms Involved in the Selection of HIV-1 Reverse Transcriptase Thumb Subdomain Polymorphisms Associated with Nucleoside Analogue Therapy Failure
Authors: Betancor Gilberto , Puertas Maria C. , Nevot María , Garriga César , Martínez Miguel A. , Martinez-Picado Javier , Menéndez-Arias Luis 
Published: August 2010

ABSTRACTPrevious studies showed an increased prevalence of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) thumb subdomain polymorphisms Pro272, Arg277, and Thr286 in patients failing therapy with nucleoside analogue combinations. Interestingly, wild-type HIV-1BH10RT contains Pro272, Arg277, and Thr286. Here, we demonstrate that in the presence of zidovudine, HIV-1BH10RT mutations P272A/R277K/T286A produce a significant reduction of the viral replication capacity in peripheral blood mononuclear cells in both the absence and presence of M41L/T215Y. In studies carried out with recombinant enzymes, we show that RT thumb subdomain mutations decrease primer-unblocking activity on RNA/DNA complexes, but not on DNA/DNA template-primers. These effects were observed with primers terminated with thymidine analogues (i.e., zidovudine and stavudine) and carbovir (the relevant derivative of abacavir) and were more pronounced when mutations were introduced in the wild-type HIV-1BH10RT sequence context. RT thumb subdomain mutations increased by 2-fold the apparent dissociation equilibrium constant (Kd) for RNA/DNA without affecting theKdfor DNA/DNA substrates. RNase H assays carried out with RNA/DNA complexes did not reveal an increase in the reaction rate or in secondary cleavage events that could account for the decreased excision activity. The interaction of Arg277 with the phosphate backbone of the RNA template in HIV-1 RT bound to RNA/DNA and the location of Thr286 close to the RNA strand are consistent with thumb polymorphisms playing a role in decreasing nucleoside RT inhibitor excision activity on RNA/DNA template-primers by affecting interactions with the template-primer duplex without involvement of the RNase H activity of the enzyme.
In Vivo
and
In Vitro
Sensitivity of
Fasciola hepatica
to Triclabendazole Combined with Artesunate, Artemether, or OZ78
Authors: Duthaler Urs , Smith Thomas A. , Keiser Jennifer 
Published: August 2010

ABSTRACT

Triclabendazole resistance is continually documented from livestock, and hence new treatment strategies for
Fasciola hepatica
infections are needed. We investigated the effect of triclabendazole combined with artesunate, artemether, or OZ78 compared to that of monotherapy against adult and juvenile
F. hepatica
in rats.
In vitro
experiments with triclabendazole and its sulfoxide and sulfone metabolites, each in combination with the peroxides, complemented our study.
F. hepatica
-infected rats were subjected to single drugs or drug combinations 3 to 4 weeks (juvenile flukes) and >8 weeks (adult flukes) postinfection. Negative binomial regressions of worm and egg counts were used to analyze dose-response relationships and whether the effects of drug combinations were synergistic or antagonistic. The
in vitro
assays were evaluated by means of viability scales based on fluke motility. Fifty percent effective dose values of 113.0, 77.7, 22.9, and 2.7 mg/kg of body weight were calculated for monotherapy with artesunate, artemether, OZ78, and triclabendazole, respectively, against adult
F. hepatica
. Likelihood ratio tests revealed synergistic interactions (
P
< 0.05) of combinations of triclabendazole (2.5 mg/kg) plus artesunate or artemether on adult worm burden. Antagonistic effects on the adult burden and egg output were observed when a lower triclabendazole dose (1.25 mg/kg) was combined with the artemisinins. No significant interactions (
P
= 0.07) were observed for OZ78 and triclabendazole combinations and between the triclabendazole effect and the effects of the other partner drugs on juvenile worms. Our
in vitro
studies of adult worms agreed with the
in vivo
results, while the
in vitro
analysis of juvenile worms revealed greater interactions than observed
in vivo
. In conclusion, single-agent triclabendazole demonstrated a more potent
in vivo
and
in vitro
fasciocidal activity than the experimental drugs artesunate, artemether, and OZ78. When combined, synergistic but also antagonistic effects depending on the doses administered were observed, which should be elucidated in more detail in future studies.
Stent-assisted coiling of paraclinoid aneurysms: risks and effectiveness
Authors: Ogilvy Christopher S , Natarajan Sabareesh K , Jahshan Shady , Karmon Yuval , Yang Xinyu , Snyder Kenneth V , Hopkins L Nelson , Siddiqui Adnan H , Levy Elad I 
Published: August 2010

BackgroundStent assistance for treatment of wide-based aneurysms is becoming rapidly accepted.MethodsCases of aneurysms arising in the paraclinoid location of the internal carotid artery treated with intracranial stents and/or bare platinum coils were analyzed retrospectively from our prospectively collected database. We identified 70 aneurysms treated with stent assistance (including one stenting-alone case) and 24 aneurysms treated with coiling alone. Stenting-assisted coiling was achieved either as a one-time treatment or as a two-step maneuver with the stent placed several weeks before coiling, or stent-assisted coiling was used as a second maneuver in aneurysms that recanalized after previous coiling.ResultsIn aneurysms treated with stent assistance, 60% had ≥95% occlusion at treatment completion, a result comparing favorably with the 54.2% rate of ≥95% occlusion associated with coiling alone. At last follow-up, 60 aneurysms treated with stent assistance had a 66.7% incidence of ≥95% occlusion, with no in-stent stenosis; 75% of patients treated with coiling alone had ≥95% aneurysm occlusion. Thrombus occurred during stent deployment in two patients, one with and one without neurologic sequelae; stent displacement occurred in one patient without neurologic sequelae. At last follow-up, 57 of 62 patients (91.9%) treated with stent-assisted coiling experienced excellent/good outcomes (modified Rankin scale score ≤2). These results compared favorably with those for the coiling-alone group in which 23 of 24 (95.8%) had good outcomes.ConclusionStent-assisted coiling of paraclinoid aneurysms did not add significantly to morbidity; overall effectiveness was comparable to that of bare coiling of paraclinoid aneurysms. These results require confirmation by a prospective controlled trial.
Dynamo
Authors: DeCandia Giuseppe , Hastorun Deniz , Jampani Madan , Kakulapati Gunavardhan , Lakshman Avinash , Pilchin Alex , Sivasubramanian Swaminathan , Vosshall Peter , Vogels Werner 
Published: August 2010

Reliability at massive scale is one of the biggest challenges we face at Amazon.com, one of the largest e-commerce operations in the world; even the slightest outage has significant financial consequences and impacts customer trust. The Amazon.com platform, which provides services for many web sites worldwide, is implemented on top of an infrastructure of tens of thousands of servers and network components located in many datacenters around the world. At this scale, small and large components fail continuously and the way persistent state is managed in the face of these failures drives the reliability and scalability of the software systems.
This paper presents the design and implementation of Dynamo, a highly available key-value storage system that some of Amazon's core services use to provide an "always-on" experience. To achieve this level of availability, Dynamo sacrifices consistency under certain failure scenarios. It makes extensive use of object versioning and application-assisted conflict resolution in a manner that provides a novel interface for developers to use.
High-level small-step operational semantics for transactions
Authors: Moore Katherine F. , Grossman Dan 
Published: August 2010

Software transactions have received significant attention as a way to simplify shared-memory concurrent programming, but insufficient focus has been given to the precise meaning of software transactions or their interaction with other language features. This work begins to rectify that situation by presenting a family of formal languages that model a wide variety of behaviors for software transactions. These languages abstract away implementation details of transactional memory, providing high-level definitions suitable for programming languages. We use small-step semantics in order to represent explicitly the interleaved execution of threads that is necessary to investigate pertinent issues.
We demonstrate the value of our core approach to modeling transactions by investigating two issues in depth. First, we consider parallel nesting, in which parallelism and transactions can nest arbitrarily. Second, we present multiple models for weak isolation, in which nontransactional code can violate the isolation of a transaction. For both, type-and-effect systems let us soundly and statically restrict what computation can occur inside or outside a transaction. We prove some key language-equivalence theorems to confirm that under sufficient static restrictions, in particular that each mutable memory location is used outside transactions or inside transactions (but not both), no program can determine whether the language implementation uses weak isolation or strong isolation.
Automatic inference of stationary fields
Authors: Unkel Christopher , Lam Monica S. 
Published: August 2010

Java programmers can document that the relationship between two objects is unchanging by declaring the field that encodes that relationship to be final. This information can be used in program understanding and detection of errors in new code additions. Unfortunately, few fields in programs are actually declared final. Programs often contain fields that could be final, but are not declared so. Moreover, the definition of final has restrictions on initializationthat limit its applicability.

We introduce
stationary
fields as a generalization of final. A field in a program is stationary if, for every object that contains it, all writes to the field occur before all the reads. Unlike the definition of final fields, there can be multiple writes during initialization, and initialization can span multiple methods.

We have developed an efficient algorithm for inferring which fields are stationary in a program, based on the observation that many fields acquire their value very close to object creation. We presume that an object's initialization phase has concluded when its reference is saved in some heap object. We perform precise analysis only regarding recently created objects. Applying our algorithm to real-world Java programs demonstrates that stationary fields are more common than final fields: 44-59% vs. 11-17% respectively in our benchmarks.
These surprising results have several significant implications. First, substantial portions of Java programs appear to be written in a functional style. Second, initialization of these fields occurs very close to object creation, when very good alias information is available. These results open the door for more accurate and efficient pointer alias analysis.
Demand-driven alias analysis for C
Authors: Zheng Xin , Rugina Radu 
Published: August 2010

This paper presents a demand-driven, flow-insensitive analysisalgorithm for answering may-alias queries. We formulate thecomputation of alias queries as a CFL-reachability problem, and use this formulation to derive a demand-driven analysis algorithm. The analysis uses a worklist algorithm that gradually explores the program structure and stops as soon as enough evidence is gathered to answer the query. Unlike existing techniques, our approach does not require building or intersecting points-to sets.
Experiments show that our technique is effective at answering alias queries accurately and efficiently in a demand-driven fashion. For a set of alias queries from the SPEC2000 benchmarks, an implementation of our analysis is able to accurately answer 96% of the queries in 0.5 milliseconds per query on average, using only 65 KB of memory. Compared to a demand-driven points-to analysis that constructs and intersects points-to sets on the fly, our alias analysis can achieve better accuracy while running more than 30 times faster. The low run-time cost and low memory demands of the analysis make it a very good candidate not only for compilers, but also for interactive tools, such as program understanding tools or integrated development environments (IDEs).
Generating precise and concise procedure summaries
Authors: Yorsh Greta , Yahav Eran , Chandra Satish 
Published: August 2010

We present a framework for generating procedure summaries that are (a) precise - applying the summary in a given context yields the same result as re-analyzing the procedure in that context, and(b) concise - the summary exploits the commonalitiesin the ways the procedure manipulates abstract values, and does not contain superfluous context information.
The use of a precise and concise procedure summary inmodular analyses provides a way to capture infinitely many possible contexts in a finite way; in interprocedural analyses, it provides a compact representation of an explicit input-output summary table without loss of precision.
We define a class of abstract domains and transformers for which precise and concise summaries can be efficiently generated using our framework. Our framework is rich enough to encode a wide range of problems, including all IFDS and IDE problems. In addition, we show how the framework is instantiated to provide novel solutions to two hard problems: modular linear constant propagation and modular typestate verification, both in the presence of aliasing. We implemented a prototype of our framework that computes summaries for the typestate domain, and report on preliminary experimental results.
A theory of contracts for web services
Authors: Castagna Giuseppe , Gesbert Nils , Padovani Luca 
Published: August 2010

Contracts are behavioural descriptions of Web services. We devise a theory of contracts that formalises the compatibility of a client to a service, and the safe replacement of a service with another service. The use of contracts statically ensures the successful completion of every possible interaction between compatible clients and services.
The technical device that underlies the theory is the definition of filters, which are explicit coercions that prevent some possible behaviours of services and, in doing so, they make services compatible with different usage scenarios. We show that filters can be seen as proofs of a sound and complete subcontracting deduction system which simultaneously refines and extends Hennessy's classical axiomatisation of the must testing preorder. The relation is decidable and the decision algorithm is obtained via a cut-elimination process that proves the coherence of subcontracting as a logical system.
Despite the richness of the technical development, the resulting approach is based on simple ideas and basic intuitions. Remarkably, its application is mostly independent of the language used to program the services or the clients. We also outline the possible practical impact of such a work and the perspectives of future research it opens.