bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two self‐referencing methods for the measurement of beam spot position
Authors: Nyiri Balazs J. , Smale Jason R. , Gerig Lee H. 
Published: December 2012

Purpose:Two quantitative methods of measuring electron beam spot position with respect to the collimator axis of rotation (CAOR) are described.Methods:Method 1 uses a cylindrical ion chamber (IC) mounted on a jig corotational with the collimator making the relationship among the chamber, jaws, and CAOR fixed and independent of collimator angle. A jaw parallel to the IC axis is set to zero and the IC position adjusted so that the IC signal is approximately 50% of the open field value, providing a large dose gradient in the region of the IC. The cGy/MU value is measured as a function of collimator rotation, e.g., every 30°. If the beam spot does not lie on the CAOR, the signal from the ion chamber will vary with collimator rotation. Based on a measured spatial sensitivity, the distance of the beam spot from the CAOR can be calculated from the IC signal variation with rotation. The 2nd method is image based. Two stainless steel rods, 3 mm in diameter, are mounted to a jig attached to the Linac collimator. The rods, offset from the CAOR, lay in different planes normal to the CAOR, one at 158 cm SSD and the other at 70 cm SSD. As the collimator rotates the rods move tangent along an envelope circle, the centers of which are on the CAOR in their respective planes. Three images, each at a different collimator rotation, containing the shadows of both rods, are acquired on the Linac EPID. At each angle the shadow of the rods on the EPID defines lines tangent to the projection of the envelope circles. From these the authors determine the projected centers of the two circles at different heights. From the distance of these two points using the two heights and the source to EPID distance, the authors calculate the distance of the beam spot from the CAOR. Measurements with all two techniques were performed on an Elekta Linac. Measurements were performed with the beam spot in nominal clinical position and in a deliberately offset position. Measurements were also performed using the Flexmap image registration/ball‐bearing test.Results:Within their uncertainties, both methods report the same beam spot displacement. In clinical use, a total of 203 monthly beam spot measurements on 14 different beams showed an average displacement of 0.11 mm (σ = 0.07 mm) in‐plane and 0.10 mm (σ = 0.07 mm) cross‐plane with maximum displacement of 0.37 mm in‐plane and 0.34 mm cross‐plane.Conclusions:The methods described provide a quantitative measure of beam spot position, are easy to use, and provide another tool for Linac setup and quality assurance. Fundamental to the techniques is that they are self‐referencing–i.e., they do not require the user to independently define the CAOR.
Semiempirical simulation of x‐ray detectors for imaging applications
Authors: Bontempi Marco , Bettuzzi Matteo , Visani Andrea 
Published: December 2012

Purpose:The Monte Carlo (MC) simulation is widely used to design and test complex physical phenomena. This paper presents a simulator of x‐ray detector for imaging applications by providing a simple component that can be embedded into a MC code and allowing developers to focus their attention on the primary goals without hanging in the quality of the final output image.Methods:A simplified semiempirical model of x‐ray detector was developed and implemented starting from the definition of absorber material and developing scintillator and photoconductor screens and detectors. The validation was done by comparing a Hamamatsu C10900D digital flat panel with a simulation of the same detector using the presented model: MTF, nNPS, and NEQ.Results:The results of validation tests shown excellent agreement of the simulation with respect to the experimental data. The simulation was fast and efficient even in older computers (2004) and it was excellent in newer multicore computers (2010).Conclusions:Comparisons between experimental data and simulations shown that the simulator is able to mimic the output of a real imaging system, and it can have many applications in fields such as industry, medical physics, and teaching.
Efficacy of Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010
Authors: Leang Rithea , Barrette Amy , Bouth Denis Mey , Menard Didier , Abdur Rashid , Duong Socheat , Ringwald Pascal 
Published: December 2012

ABSTRACT

We describe here the results of antimalarial therapeutic efficacy studies conducted in Cambodia from 2008 to 2010. A total of 15 studies in four sentinel sites were conducted using dihydroartemisinin-piperaquine (DP) for the treatment of
Plasmodium falciparum
infection and chloroquine (CQ) and DP for the treatment of
P. vivax
infection. All studies were performed according to the standard World Health Organization protocol for the assessment of antimalarial treatment efficacy. Among the studies of DP for the treatment of
P. falciparum
, an increase in treatment failure was observed in the western provinces. In 2010, the PCR-corrected treatment failure rates for DP on day 42 were 25% (95% confidence interval [CI] = 10 to 51%) in Pailin and 10.7% (95% CI = 4 to 23%) in Pursat, while the therapeutic efficacy of DP remained high (100%) in Ratanakiri and Preah Vihear provinces, located in northern and eastern Cambodia. For the studies of
P. vivax
, the day 28 uncorrected treatment failure rate among patients treated with CQ ranged from 4.4 to 17.4%; DP remained 100% effective in all sites. Further study is required to investigate suspected
P. falciparum
resistance to piperaquine in western Cambodia; the results of
in vitro
and molecular studies were not found to support the therapeutic efficacy findings. The emergence of artemisinin resistance in this region has likely put additional pressure on piperaquine. Although DP appears to be an appropriate new first-line treatment for
P. vivax
in Cambodia, alternative treatments are urgently needed for
P. falciparum
-infected patients in western Cambodia.
Chemobiosynthesis of New Antimalarial Macrolides
Authors: Goodman Christopher D. , Useglio Mariana , Peirú Salvador , Labadie Guillermo R. , McFadden Geoffrey I. , Rodríguez Eduardo , Gramajo Hugo 
Published: December 2012

ABSTRACT

We have synthesized new derivatives of the macrolide antibiotics erythromycin and azithromycin. Novel deoxysugar moieties were attached to these standard antibiotics by biotransformation using a heterologous host. The resulting compounds were tested against several standard laboratory and clinically isolated bacterial strains. In addition, they were also tested
in vitro
against standard and drug-resistant strains of human malaria parasites (
Plasmodium falciparum
) and the liver stages of the rodent malaria parasite (
Plasmodium berghei
). Antibacterial activity of modified erythromycin and azithromycin showed no improvement over the unmodified macrolides, but the modified compounds showed a 10-fold increase in effectiveness after a short-term exposure against blood stages of malaria. The new compounds also remained active against azithromycin-resistant strains of
P. falciparum
and inhibited growth of liver-stage parasites at concentrations similar to those used for primaquine. Our findings show that malaria parasites have two distinct responses to macrolide antibiotics, one reflecting the prokaryotic origin of the apicoplast and a second, as-yet uncharacterized response that we attribute to the eukaryotic nature of the parasite. This is the first report for macrolides that target two different functions in the
Plasmodium
parasites.
NVC-422 Inactivates Staphylococcus aureus Toxins
Authors: Jekle Andreas , Yoon Jungjoo , Zuck Meghan , Najafi Ramin , Wang Lu , Shiau Timothy , Francavilla Charles , Rani Suriani Abdul , Eitzinger Christian , Nagl Markus , Anderson Mark , Debabov Dmitri 
Published: December 2012

ABSTRACT

Bacterial pathogens have specific virulence factors (e.g., toxins) that contribute significantly to the virulence and infectivity of microorganisms within the human hosts. Virulence factors are molecules expressed by pathogens that enable colonization, immunoevasion, and immunosuppression, obtaining nutrients from the host or gaining entry into host cells. They can cause pathogenesis by inhibiting or stimulating certain host functions. For example, in systemic
Staphylococcus aureus
infections, virulence factors such as toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxin A (SEA), and staphylococcal enterotoxin B (SEB) cause sepsis or toxic shock by uncontrolled stimulation of T lymphocytes and by triggering a cytokine storm.
In vitro
, these superantigens stimulate the proliferation of human peripheral blood mononuclear cells (PBMC) and the release of many cytokines. NVC-422 (
N
,
N
-dichloro-2,2-dimethyltaurine) is a broad-spectrum, fast-acting topical anti-infective agent against microbial pathogens, including antibiotic-resistant microbes. Using mass spectrometry, we demonstrate here that NVC-422 oxidizes methionine residues of TSST-1, SEA, SEB, and exfoliative toxin A (ETA). Exposure of virulence factors to 0.1% NVC-422 for 1 h prevented TSST-1-, SEA-, SEB-, and ETA-induced cell proliferation and cytokine release. Moreover, NVC-422 also delayed and reduced the protein A- and clumping factor-associated agglutination of
S. aureus
cultures. These results show that, in addition to its well-described direct microbicidal activity, NVC-422 can inactivate
S. aureus
virulence factors through rapid oxidation of methionines.
'Computing, we have a problem …'
Authors: Camp Tracy 
Published: December 2012

In May 2005, Jim Foley (Board Chair of the Computing Research Association) published an abstract that was titled with these words: "Computing, We Have a Problem …". The main purpose of Dr. Foley's article was to discuss the image problem within computing, that "the public does not fully understand, and hence does not appreciate, what computing is and why computing and computing research are important" [1]. He then considered the consequences of this image problem (e.g., decreased enrollments in computing degree programs) and stated what CRA planned to do to rectify the situation.While Dr. Foley's article did not mention women, minorities, or persons with disabilities, it is clear that several groups in our society are tremendously impacted by the image problem that exists within computing. In this article, we begin by discussing the lack of participation that exists for those who are trained in computing (i.e., people who have the skills to develop computer hardware and software). We then discuss why this digital divide should be of high concern to everyone, what we can learn from other previously male-dominated fields, what you can do to help improve the current situation, and what the future might hold.
The Role of JAK Pathway Dysregulation in the Pathogenesis and Treatment of Acute Myeloid Leukemia
Authors: Lee Hun Ju , Daver Naval , Kantarjian Hagop M. , Verstovsek Srdan , Ravandi Farhad 
Published: December 2012

AbstractThe discovery of the Janus kinase 2 (JAK2) V617F mutation has improved our understanding of the pathophysiology of myeloproliferative neoplasms such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Before discovery of the JAK2 V617F mutation, there were no specific targeted therapies for patients with myeloproliferative neoplasms. More recently, several small-molecule inhibitors have been developed that have shown therapeutic potential in the clinical setting. There is evidence that the JAK2 pathway is dysregulated in some acute myeloid leukemias and may also represent a novel therapeutic target in this disease. In this review, we describe the preclinical, clinical, and pathophysiologic evidence for using JAK inhibitors in the treatment of acute myeloid leukemias. Clin Cancer Res; 19(2); 327–35. ©2012 AACR.
Estimating Central Equatorial Pacific SST Variability over the Past Millennium. Part II: Reconstructions and Implications
Authors: Emile-Geay Julien , Cobb Kimberly M. , Mann Michael E. , Wittenberg Andrew T. 
Published: December 2012

AbstractReducing the uncertainties surrounding the impacts of anthropogenic climate change requires vetting general circulation models (GCMs) against long records of past natural climate variability. This is particularly challenging in the tropical Pacific Ocean, where short, sparse instrumental data preclude GCM validation on multidecadal to centennial time scales. This two-part paper demonstrates the application of two statistical methodologies to a network of accurately dated tropical climate records to reconstruct sea surface temperature (SST) variability in the Niño-3.4 region over the past millennium. While Part I described the methods and established their validity and limitations, this paper presents several reconstructions of Niño-3.4, analyzes their sensitivity to procedural choices and input data, and compares them to climate forcing time series and previously published tropical Pacific SST reconstructions. The reconstructions herein show remarkably similar behavior at decadal to multidecadal scales, but diverge markedly on centennial scales. The amplitude of centennial variability in each reconstruction scales with the magnitude of the A.D. 1860–1995 trend in the target dataset’s Niño-3.4 index, with Extended Reconstructed SST, version 3 (ERSSTv3) > the Second Hadley Centre SST dataset (HadSST2) > Kaplan SST; these discrepancies constitute a major source of uncertainty in reconstructing preinstrumental Niño-3.4 SST. Despite inevitable variance losses, the reconstructed multidecadal variability exceeds that simulated by a state-of-the-art GCM (forced and unforced) over the past millennium, while reconstructed centennial variability is incompatible with constant boundary conditions. Wavelet coherence analysis reveals a robust antiphasing between solar forcing and Niño-3.4 SST on bicentennial time scales, but not on shorter time scales. Implications for GCM representations of the tropical Pacific climate response to radiative forcing are then discussed.
Model Bias Reduction and the Limits of Oceanic Decadal Predictability: Importance of the Deep Ocean
Authors: Sévellec Florian , Fedorov Alexey V. 
Published: December 2012

Abstract
Ocean general circulation models (GCMs), as part of comprehensive climate models, are extensively used for experimental decadal climate prediction. Understanding the limits of decadal ocean predictability is critical for making progress in these efforts. However, when forced with observed fields at the surface, ocean models develop biases in temperature and salinity. Here, the authors ask two complementary questions related to both decadal prediction and model bias: 1) Can the bias be temporarily reduced and the prediction improved by perturbing the initial conditions? 2) How fast will such initial perturbations grow? To answer these questions, the authors use a realistic ocean GCM and compute temperature and salinity perturbations that reduce the model bias most efficiently during a given time interval. The authors find that to reduce this bias, especially pronounced in the upper ocean above 1000 m, initial perturbations should be imposed in the deep ocean (specifically, in the Southern Ocean). Over 14 yr, a 0.1-K perturbation in the deep ocean can induce a temperature anomaly of several kelvins in the upper ocean, partially reducing the bias. A corollary of these results is that small initialization errors in the deep ocean can produce large errors in the upper-ocean temperature on decadal time scales, which can be interpreted as a decadal predictability barrier associated with ocean dynamics. To study the mechanisms of the perturbation growth, the authors formulate an idealized model describing temperature anomalies in the Southern Ocean. The results indicate that the strong mean meridional temperature gradient in this region enhances the sensitivity of the upper ocean to deep-ocean perturbations through nonnormal dynamics generating pronounced stationary-wave patterns.
CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia
Authors: McNerney Megan E. , Brown Christopher D. , Wang Xiaoyue , Bartom Elizabeth T. , Karmakar Subhradip , Bandlamudi Chaitanya , Yu Shan , Ko Jinkyung , Sandall Barry P. , Stricker Thomas , Anastasi John , Grossman Robert L. , Cunningham John M. , Le Beau Michelle M. , White Kevin P. 
Published: December 2012

Key PointsCUX1 is a transcription factor encoded on a region of chromosome 7 that is frequently deleted in high-risk acute myeloid leukemia. Haploinsufficiency of CUX1/cut promotes hematopoietic overgrowth in both Drosophila melanogaster and human xenograft mouse models in vivo.
Phase 1 trial of IL-15 trans presentation blockade using humanized Mik-Beta-1 mAb in patients with T-cell large granular lymphocytic leukemia
Authors: Waldmann Thomas A. , Conlon Kevin C. , Stewart Donn M. , Worthy TatYana A. , Janik John E. , Fleisher Thomas A. , Albert Paul S. , Figg William D. , Spencer Shawn D. , Raffeld Mark , Decker Jean R. , Goldman Carolyn K. , Bryant Bonita R. , Petrus Michael N. , Creekmore Stephen P. , Morris John C. 
Published: December 2012

AbstractIn the present study, Hu-Mikβ1, a humanized mAb directed at the shared IL-2/IL-15Rβ subunit (CD122) was evaluated in patients with T-cell large granular lymphocytic (T-LGL) leukemia. Hu-Mikβ1 blocked the trans presentation of IL-15 to T cells expressing IL-2/IL-15Rβ and the common γ-chain (CD132), but did not block IL-15 action in cells that expressed the heterotrimeric IL-15 receptor in cis. There was no significant toxicity associated with Hu-Mikβ1 administration in patients with T-LGL leukemia, but no major clinical responses were observed. One patient who had previously received murine Mikβ1 developed a measurable Ab response to the infused Ab. Nevertheless, the safety profile of this first in-human study of the humanized mAb to IL-2/IL-15Rβ (CD122) supports its evaluation in disorders such as refractory celiac disease, in which IL-15 and its receptor have been proposed to play a critical role in the pathogenesis and maintenance of disease activity. The protocol is registered with www.clinicaltrials.gov as number NCT 00076180.
Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer
Authors: Suzumura Tomohiro , Kimura Tatsuo , Kudoh Shinzoh , Umekawa Kanako , Nagata Misato , Matsuura Kuniomi , Tanaka Hidenori , Mitsuoka Shigeki , Yoshimura Naruo , Kira Yukimi , Nakai Toshiyuki , Hirata Kazuto 
Published: December 2012

Abstract

Background
Rash, liver dysfunction, and diarrhea are known major adverse events associated with erlotinib and gefitinib. However, clinical trials with gefitinib have reported different proportions of adverse events compared to trials with erlotinib. In an in vitro study, cytochrome P450 (CYP) 2D6 was shown to be involved in the metabolism of gefitinib but not erlotinib. It has been hypothesized that CYP2D6 phenotypes may be implicated in different adverse events associated with gefitinib and erlotinib therapies.

Methods
The frequency of each adverse event was evaluated during the period in which the patients received gefitinib or erlotinib therapy. CYP2D6 phenotypes were determined by analysis of CYP2D6 genotypes using real-time polymerase chain reaction techniques, which can detect single-nucleotide polymorphisms. The CYP2D6 phenotypes were categorized into 2 groups according to functional or reduced metabolic levels. In addition, we evaluated the odds ratio (OR) of the adverse events associated with each factor, including CYP2D6 activities and treatment types.

Results
A total of 232 patients received gefitinib therapy, and 86 received erlotinib therapy. Reduced function of CYP2D6 was associated with an increased risk of rash of grade 2 or more (OR, 0.44; 95% confidence interval [CI], 0.21–0.94; *p = 0.03), but not diarrhea ≥ grade 2 (OR, 0.49; 95% CI, 0.17–1.51; *p = 0.20) or liver dysfunction ≥ grade 2 (OR, 1.08; 95% CI, 0.52–2.34; *p = 0.84) in the gefitinib cohort. No associations were observed between any adverse events in the erlotinib cohort and CYP2D6 phenotypes (rash: OR, 1.77; 95% CI, 0.54–6.41; *p = 0.35/diarrhea: OR, 1.08; 95% CI, 0.21–7.43; *p = 0.93/liver dysfunction: OR, 0.93; 95% CI, 0.20–5.07; *p = 0.93).

Conclusions
The frequency of rash was significantly higher in patients with reduced CYP2D6 activity who treated with gefitinib compared to patients with functional CYP2D6. CYP2D6 phenotypes are a risk factor for the development of rash in response to gefitinib therapy.
Ethanol extract of Gleditsia sinensis thorn suppresses angiogenesis in vitro and in vivo
Authors: Yi Jin-Mu , Park Jong-Shik , Oh Se-Mi , Lee Jun , Kim Jinhee , Oh Dal-Seok , Bang Ok-Sun , Kim No Soo 
Published: December 2012

AbstractBackgroundGleditsia sinensisthorns have been widely used in traditional Korean medicine for the treatment of several diseases, including obesity, thrombosis, and tumor-related diseases. The aim of the study is to determine the antiangiogenic effect ofGleditsia sinensisthornsin vitroandin vivoin a bid to evaluate its potential as an anticancer drug.MethodsEthanol extract ofGleditsia sinensisthorns (EEGS) were prepared and used forin vitroandin vivoassays.In vitroantiangiogenic effect of EEGS was determined in HUVEC primary cells by cell migration and tube formation assays.In vivoantiangiogenic effect of EEGS was determined by measuring vessel formation and vascular endothelial cells migrating into the implanted matrigels in nude mice. The angiogenesis-related proteins of which expression levels were altered by EEGS were identified by proteomic analysis.ResultsEEGS exerted a dose-dependent antiproliferative effect on HUVEC cells without significant cytotoxicity. Angiogenic properties, such as cell migration and tube formation, were significantly inhibited by EEGS in a dose-dependent manner. New vessel formation was also suppressed by EEGS, as determined by the directedin vivoangiogenesis assays in nude mice. EEGS reduced the expression of proangiogenic proteins, endothelin 1 and matrix metallopeptidase 2, in HUVEC cells.ConclusionsOur findings suggest that EEGS can inhibit angiogenesis by down-regulating proangiogenic proteins, and therefore it should be considered as a potential anticancer drug targeting tumor-derived angiogenesis.