bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental analysis of general ion recombination in a liquid‐filled ionization chamber in high‐energy photon beams
Authors: Chung Eunah , Davis Stephen , Seuntjens Jan 
Published: May 2013

Purpose:To study experimentally the general ion recombination effect in a liquid‐filled ionization chamber (LIC) in high‐energy photon beams.Methods:The general ion recombination effect on the response of a micro liquid ion chamber (microLion) was investigated with a 6 MV photon beam in normal and SRS modes produced from a Varian® Novalis TxTM linear accelerator. Dose rates of the linear accelerator were set to 100, 400, and 1000 MU/min, which correspond to pulse repetition frequencies of 60, 240, and 600 Hz, respectively. Polarization voltages applied to the microLion were +800 and +400 V. The relative collection efficiency of the microLion response as a function of dose per pulse was experimentally measured with changing polarization voltage and pulse repetition frequencies and was compared with the theoretically calculated value.Results:For the 60 Hz pulse repetition frequency, the experimental relative collection efficiency was not different from the theoretical one for a pulsed beam more than 0.3% for both polarization voltages. For a pulsed radiation beam with a higher pulse repetition frequency, the experimental relative collection efficiency converged to the theoretically calculated efficiency for continuous beams. This result indicates that the response of the microLion tends toward the response to a continuous beam with increasing pulse repetition frequency of a pulsed beam because of low ion mobility in the liquid.Conclusions:This work suggests an empirical method to correct for differences in general ion recombination of a LIC between different radiation fields. More work is needed to quantitatively explain the LIC general ion recombination behavior in pulsed beams generated from linear accelerators.
The Polyphosphate Kinase Gene
ppk2
Is Required for Mycobacterium tuberculosis Inorganic Polyphosphate Regulation and Virulence
Authors: Chuang Yu-Min , Belchis Deborah A. , Karakousis Petros C. 
Published: May 2013

ABSTRACT

The
Mycobacterium tuberculosis
gene
Rv3232c
/
MT3329
(
ppk2
) encodes a class II polyphosphate kinase, which hydrolyzes inorganic polyphosphate (poly P) to synthesize GTP. We assessed the role of
ppk2
in
M. tuberculosis
poly P regulation, antibiotic tolerance, and virulence. A
ppk2
-deficient mutant (
ppk2
::Tn) and its isogenic wild-type (WT) and complemented (Comp) strains were studied. For each strain, the intrabacillary poly P content, MIC of isoniazid, and growth kinetics during infection of J774 macrophages were determined. Multiplex immunobead assays were used to evaluate cytokines elaborated during macrophage infection. The requirement of
ppk2
for
M. tuberculosis
virulence was assessed in the murine model. The
ppk2
::Tn mutant was found to have significantly increased poly P content and a 4-fold increase in the MIC of isoniazid relative to the WT and Comp strains. The
ppk2
::Tn mutant showed reduced survival at day 7 in activated and naive J774 macrophages relative to the WT. Naive
ppk2
::Tn mutant-infected macrophages showed increased expression of interleukin 2 (IL-2), IL-9, IL-10, IL-12p70, and gamma interferon (IFN-γ) relative to WT-infected macrophages. The
ppk2
::Tn mutant exhibited significantly lower lung CFU during acute murine infection compared to the control groups.
ppk2
is required for control of intrabacillary poly P levels and optimal
M. tuberculosis
growth and survival in macrophages and mouse lungs.

IMPORTANCE
Mycobacterium tuberculosis
, the causative agent of tuberculosis (TB), is a highly successful human pathogen because it has developed mechanisms to multiply and survive in the lungs by circumventing the immune system. Identification of virulence factors responsible for
M. tuberculosis
growth and persistence in host tissues may assist in the development of novel strategies to treat TB. In this study, we found that the mycobacterial enzyme polyphosphate kinase 2 (PPK2) is required for controlling intracellular levels of important regulatory molecules and for maintaining susceptibility to the first-line anti-TB drug isoniazid. In addition, PPK2 was found to be required for
M. tuberculosis
growth in the lungs of mice, at least in part by suppressing the expression of certain key cytokines and chemokines by inactivated lung macrophages.
Physiological and Genetic Description of Dissimilatory Perchlorate Reduction by the Novel Marine Bacterium
Arcobacter
sp. Strain CAB
Authors: Carlström Charlotte I. , Wang Ouwei , Melnyk Ryan A. , Bauer Stefan , Lee Joyce , Engelbrektson Anna , Coates John D. 
Published: May 2013

ABSTRACT

A novel dissimilatory perchlorate-reducing bacterium (DPRB),
Arcobacter
sp. strain CAB, was isolated from a marina in Berkeley, CA. Phylogenetically, this halophile was most closely related to
Arcobacter defluvii
strain SW30-2 and
Arcobacter ellisii
. With acetate as the electron donor, strain CAB completely reduced perchlorate (ClO
4
−
) or chlorate (ClO
3
−
) [collectively designated (per)chlorate] to innocuous chloride (Cl
−
), likely using the perchlorate reductase (Pcr) and chlorite dismutase (Cld) enzymes. When grown with perchlorate, optimum growth was observed at 25 to 30°C, pH 7, and 3% NaCl. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) preparations were dominated by free-swimming straight rods with 1 to 2 polar flagella per cell. Strain CAB utilized a variety of organic acids, fructose, and hydrogen as electron donors coupled to (per)chlorate reduction. Further, under anoxic growth conditions strain CAB utilized the biogenic oxygen produced as a result of chlorite dismutation to oxidize catechol via the
meta
-cleavage pathway of aerobic catechol degradation and the catechol 2,3-dioxygenase enzyme. In addition to (per)chlorate, oxygen and nitrate were alternatively used as electron acceptors. The 3.48-Mb draft genome encoded a distinct perchlorate reduction island (PRI) containing several transposases. The genome lacks the
pcrC
gene, which was previously thought to be essential for (per)chlorate reduction, and appears to use an unrelated
Arcobacter c
-type cytochrome to perform the same function.

IMPORTANCE
The study of dissimilatory perchlorate-reducing bacteria (DPRB) has largely focused on freshwater, mesophilic, neutral-pH environments. This study identifies a novel marine DPRB in the genus
Arcobacter
that represents the first description of a DPRB associated with the
Campylobacteraceae
. Strain CAB is currently the only epsilonproteobacterial DPRB in pure culture. The genome of strain CAB lacks the
pcrC
gene found in all other DPRB tested, demonstrating a new variation on the (per)chlorate reduction pathway. The ability of strain CAB to oxidize catechol via the oxygenase-dependent
meta
-cleavage pathway in the absence of external oxygen by using the biogenic oxygen produced from the dismutation of chlorite provides a valuable model for understanding the anaerobic degradation of a broad diversity of xenobiotics which are recalcitrant to anaerobic metabolism but labile to oxygenase-dependent mechanisms.
Pyrophosphate-Fueled Na+and H+Transport in Prokaryotes
Authors: Baykov Alexander A. , Malinen Anssi M. , Luoto Heidi H. , Lahti Reijo 
Published: May 2013

SUMMARYIn its early history, life appeared to depend on pyrophosphate rather than ATP as the source of energy. Ancient membrane pyrophosphatases that couple pyrophosphate hydrolysis to active H+transport across biological membranes (H+-pyrophosphatases) have long been known in prokaryotes, plants, and protists. Recent studies have identified two evolutionarily related and widespread prokaryotic relics that can pump Na+(Na+-pyrophosphatase) or both Na+and H+(Na+,H+-pyrophosphatase). Both these transporters require Na+for pyrophosphate hydrolysis and are further activated by K+. The determination of the three-dimensional structures of H+- and Na+-pyrophosphatases has been another recent breakthrough in the studies of these cation pumps. Structural and functional studies have highlighted the major determinants of the cation specificities of membrane pyrophosphatases and their potential use in constructing transgenic stress-resistant organisms.
Provision of hormonal and long-acting reversible contraceptive services by general practices in Scotland, UK (2004–2009)
Authors: Reddy Anusha , Watson Margaret , Hannaford Philip , Lefevre Karen , Ayansina Dolapo 
Published: May 2013

BackgroundIn the UK, a large proportion of contraceptive services are provided from general practice. However, little is known about which contraceptive services are provided and to whom.Study designDescriptive serial cross-sectional study of women aged 12–55 years, registered with 191 general practices in Scotland, UK between 2004 and 2009.ResultsAnnual incidence of provision of hormonal and long-acting reversible contraceptives (LARCs) increased from 27.7% in 2004 to 30.1% in 2009. Amongst those women registered with a general practice for the full 5-year period the provision of LARCs increased from 8.8% to 12.5% (p<0.001). For the same group, the provision of emergency hormonal contraception (EHC) decreased from 5.2% to 2.6% (p<0.001).ConclusionsWith the exception of EHC, there was an increase over time in the provision of hormonal contraceptives and LARCs from general practices. It is important that a full range of contraceptive options remains easily available to women.
VEGF-C and VEGF-D Blockade Inhibits Inflammatory Skin Carcinogenesis
Authors: Alitalo Annamari K. , Proulx Steven T. , Karaman Sinem , Aebischer David , Martino Stefania , Jost Manuela , Schneider Nicole , Bry Maija , Detmar Michael 
Published: May 2013

Abstract
VEGF-C and VEGF-D were identified as lymphangiogenic growth factors and later shown to promote tumor metastasis, but their effects on carcinogenesis are poorly understood. Here, we have studied the effects of VEGF-C and VEGF-D on tumor development in the murine multistep chemical carcinogenesis model of squamous cell carcinoma by using a soluble VEGF-C/VEGF-D inhibitor. After topical treatment with a tumor initiator and repeated tumor promoter applications, transgenic mice expressing a soluble VEGF-C/VEGF-D receptor (sVEGFR-3) in the skin developed significantly fewer squamous cell tumors with a delayed onset when compared with wild-type mice or mice expressing sVEGFR-3 lacking the ligand-binding site. Epidermal proliferation was reduced in the carcinogen-treated transgenic skin, whereas epidermal keratinocyte proliferation in vitro was not affected by VEGF-C or VEGF-D, indicating indirect effects of sVEGFR-3 expression. Importantly, transgenic mouse skin was less sensitive to tumor promoter–induced inflammation, with reduced angiogenesis and blood vessel leakage. Cutaneous leukocytes, especially macrophages, were reduced in transgenic skin without major changes in macrophage polarization or blood monocyte numbers. Several macrophage-associated cytokines were also reduced in transgenic papillomas, although the dermal macrophages themselves did not express VEGFR-3. These findings indicate that VEGF-C/VEGF-D are involved in shaping the inflammatory tumor microenvironment that regulates early tumor progression. Our results support the use of VEGF-C/VEGF-D–blocking agents not only to inhibit metastatic progression, but also during the early stages of tumor growth. Cancer Res; 73(14); 4212–21. ©2013 AACR.
Circulating Adipokine Levels and Endometrial Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Luhn Patricia , Dallal Cher M. , Weiss Jocelyn M. , Black Amanda , Huang Wen-Yi , Lacey James V. , Hayes Richard B. , Stanczyk Frank Z. , Wentzensen Nicolas , Brinton Louise A. 
Published: May 2013

Abstract
Background: Circulating adipokine levels may be associated with endometrial cancer risk, yet few studies have evaluated these markers prospectively.
Methods: We conducted a nested case–control study of postmenopausal women in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n = 78,216), including 167 incident endometrial cancer cases and 327 controls that were matched on age, study center, race, study year of diagnosis, year of blood draw, time of day of blood draw, and menopausal hormone therapy (MHT) use. Adipokine and estradiol levels were categorized into tertiles (T). ORs and 95% confidence intervals (CIs) for the associations of adiponectin, leptin, and visfatin with endometrial cancer risk were estimated by conditional logistic regression, adjusting for known endometrial cancer risk factors, including body mass index (BMI) and circulating estradiol levels.
Results: Adiponectin levels were inversely associated with risk of endometrial cancer [ORT3vsT1 = 0.48; 95% CI, 0.29–0.80); Ptrend &lt; 0.01], whereas elevated leptin levels showed a positive association [2.77 (1.60–4.79); Ptrend &lt; 0.01]. These results remained significant after adjustment for estradiol, but not after further adjustment for BMI. When analyses were restricted to non-MHT users, associations of adiponectin and leptin were stronger and remained significant after adjustment for estradiol and BMI [0.25 (0.08–0.75); Ptrend = 0.01 and 4.72 (1.15–19.38); Ptrend = 0.02, respectively]. Nonsignificant positive associations were observed for visfatin.
Conclusion: Adipokines may influence endometrial cancer risk through pathways other than estrogen-mediated cell growth in postmenopausal women not currently on MHT.
Impact: Understanding how adipokines influence endometrial cancer risk may help to elucidate biological mechanisms important for the observed obesity–endometrial cancer association. Cancer Epidemiol Biomarkers Prev; 22(7); 1304–12. ©2013 AACR.
Deubiquitinase Inhibition of 19S Regulatory Particles by 4-Arylidene Curcumin Analog AC17 Causes NF-κB Inhibition and p53 Reactivation in Human Lung Cancer Cells
Authors: Zhou Binhua , Zuo Yinglin , Li Baojian , Wang Hao , Liu Hao , Wang Xianfeng , Qiu Xu , Hu Yun , Wen Shijun , Du Jun , Bu Xianzhang 
Published: May 2013

Abstract
Proteasome inhibitors have been suggested as potential anticancer agents in many clinical trials. Recent evidence indicates that proteasomal deubiquitinase (DUB) inhibitors, bearing a different mechanism from that of traditional proteasome inhibitors, would be appropriate candidates for new anticancer drug development. In the present study, we describe the deubiquitinase inhibition of 19S regulatory particles (19S RP) by AC17, a 4-arylidene curcumin analog synthesized in our laboratory. Although 4-arylidene curcumin analogs were reported to act as inhibitory κB (IκB) kinase (IKK) inhibitors, AC17 instead induced a rapid and marked accumulation of ubiquitinated proteins without inhibiting proteasome proteolytic activities. In contrast to its parent compound, curcumin, which is a proteasome proteolytic inhibitor, AC17 serves as an irreversible deubiquitinase inhibitor of 19S RP, resulting in inhibition of NF-κB pathway and reactivation of proapoptotic protein p53. In addition, in a murine xenograft model of human lung cancer A549, treatment with AC17 suppresses tumor growth in a manner associated with proteasome inhibition, NF-κB blockage, and p53 reactivation. These results suggest that 4-arylidene curcumin analogs are novel 19S deubiquitinase inhibitors with great potential for anticancer drug development. Mol Cancer Ther; 12(8); 1381–92. ©2013 AACR.
DNA Methylation Biomarkers for Noninvasive Diagnosis of Colorectal Cancer
Authors: Carmona F. Javier , Azuara Daniel , Berenguer-Llergo Antonio , Fernández Agustin F. , Biondo Sebastiano , de Oca Javier , Rodriguez-Moranta Francisco , Salazar Ramón , Villanueva Alberto , Fraga Mario F. , Guardiola Jordi , Capellá Gabriel , Esteller Manel , Moreno Victor 
Published: May 2013

Abstract
DNA methylation biomarkers for noninvasive diagnosis of colorectal cancer (CRC) and precursor lesions have been extensively studied. Different panels have been reported attempting to improve current protocols in clinical practice, although no definite biomarkers have been established.
In the present study, we have examined patient biopsies starting from a comprehensive analysis of DNA methylation differences between paired normal and tumor samples in known cancer-related genes aiming to select the best performing candidates informative for CRC diagnosis in stool samples.
Five selected markers were considered for subsequent analyses in independent biologic cohorts and in silico data sets. Among the five selected genes, three of them (AGTR1, WNT2 and SLIT2) were validated in stool DNA of affected patients with a detection sensitivity of 78% [95% confidence interval (CI), 56%–89%]. As a reference, DNA methylation of VIM and SEPT9 was evaluated in a subset of stool samples yielding sensitivities of 55% and 20%, respectively. Moreover, our panel may complement histologic and endoscopic diagnosis of inflammatory bowel disease (IBD)-associated neoplasia, as it was also efficient detecting aberrant DNA methylation in non-neoplastic tissue samples from affected patients.
This novel panel of specific methylation markers can be useful for early diagnosis of CRC using stool DNA and may help in the follow-up of high-risk patients with IBD. Cancer Prev Res; 6(7); 656–65. ©2013 AACR.
Assessment of Coronary Artery Stenosis by Coronary Angiography
Authors: Jiangping Song , Zhe Zheng , Wei Wang , Yunhu Song , Jie Huang , Hongyue Wang , Hong Zhao , Shengshou Hu 
Published: May 2013

Background—
Conventional coronary angiography (CCA) has been considered as a gold standard for the diagnosis of coronary artery diseases; however, its diagnostic accuracy is still unknown.

Methods and Results—
Between July 2004 and December 2011, 97 patients underwent CCA within 15 days before heart transplantation in Fuwai hospital. A head-to-head comparison study was performed to examine the diagnostic accuracy of CCA as compared with that of pathological coronary artery anatomy. As confirmed by pathological coronary artery anatomy, 44 (45.4%) patients had coronary artery diseases. The patient-based diagnostic accuracy evaluation showed that the area under the receiver-operating characteristic curve of CCA for detecting ≥50% stenosis was 0.91, with a sensitivity of 91%, a specificity of 93%, and high concordance (κ=0.83). A per-vessel analysis of 291 vessels yielded an AUC of 0.79, the agreement of 3 vessels >0.6 (κ statistic). The area under the receiver-operating characteristic curve was 0.88 for proximal and middle segments, and was 0.62 for distal segments, κ was calculated to detect the distal segments with lower concordance than proximal and middle segments. The patient- and vessel-based evaluations showed similar diagnostic accuracy of CCA in detecting ≥75% stenosis. Per-segment evaluation found CCA was more accurate for detecting ≥50% and ≥75% stenosis in proximal and middle segments than in distal segments, and the diagnosis ability decreased in more severe stenosis segments and more complex lesions.

Conclusions—
The accuracy of CCA is quite high in detecting coronary artery stenosis in patients- and vessels-based levels. However, the diagnosis ability decreased in more severe and complex lesions, especially for distal segments.
Sonic Hedgehog Signaling Pathway Mediates Cerebrolysin-Improved Neurological Function After Stroke
Authors: Zhang Li , Chopp Michael , Meier Dieter H. , Winter Stefan , Wang Lei , Szalad Alexandra , Lu Mei , Wei Min , Cui Yisheng , Zhang Zheng Gang 
Published: May 2013

Background and Purpose—
Cerebrolysin, a mixture of neurotrophic peptides, enhances neurogenesis and improves neurological outcome in experimental neurodegenerative diseases and stroke. The Sonic hedgehog (Shh) signaling pathway stimulates neurogenesis after stroke. The present study tests whether the Shh pathway mediates cerebrolysin-induced neurogenesis and improves neurological outcome after stroke.

Methods—
Rats subjected to embolic stroke were treated with cerebrolysin with or without cyclopamine.

Results—
Using neural progenitor cells derived from the subventricular zone of the lateral ventricle of adult rats, we found that cerebrolysin significantly increased neural progenitor cells proliferation and their differentiation into neurons and myelinating oligodendrocytes, which were associated with upregulation of Shh and its receptors patched and smoothened. Blockage of the Shh signaling pathway with a pharmacological smoothened inhibitor, cyclopamine, abolished cerebrolysin-induced in vitro neurogenesis and oligodendrogenesis. In the ischemic rats, treatment with cerebrolysin starting 24 hours after stroke significantly increased neural progenitor cell proliferation in the subventricular zone and enhanced neurogenesis, oligodendrogenesis, and axonal remodeling in the peri-infarct area. Moreover, profound neurological function improvements were observed in rats treated with cerebrolysin from week 3 to week 5 after stroke onset compared with vehicle-treated rats. However, in vivo inhibition of the Shh pathway with cyclopamine completely reversed the effects of cerebrolysin on neurorestoration and functional recovery.

Conclusions—
These results demonstrate that the Shh pathway mediates cerebrolysin-enhanced neurogenesis and white matter remodeling and improves functional recovery in rats after stroke.
Rotational Vertebral Artery Occlusion
Authors: Choi Kwang-Dong , Choi Jae-Hwan , Kim Ji-Soo , Kim Hyo Jung , Kim Min-Ji , Lee Tae-Hong , Lee Hyung , Moon In Soo , Oh Hui Jong , Kim Jae-Il 
Published: May 2013

Background and Purpose—
To elucidate the mechanisms and prognosis of rotational vertebral artery occlusion (RVAO).

Methods—
We analyzed clinical and radiological characteristics, patterns of induced nystagmus, and outcome in 21 patients (13 men, aged 29–77 years) with RVAO documented by dynamic cerebral angiography during an 8-year period at 3 University Hospitals in Korea. The follow-up periods ranged from 5 to 91 months (median, 37.5 months). Most patients (n=19; 90.5%) received conservative treatments.

Results—
All the patients developed vertigo accompanied by tinnitus (38%), fainting (24%), or blurred vision (19%). Only 12 (57.1%) patients showed the typical pattern of RVAO during dynamic cerebral angiography, a compression of the dominant vertebral artery at the C1-2 level during contralateral head rotation. The induced nystagmus was mostly downbeat with horizontal and torsional components beating toward the compressed vertebral artery side. None of the patients with conservative treatments developed posterior circulation stroke, and 4 of them (21.1%) showed resolution of symptoms during the follow-ups.

Conclusions—
RVAO has various patterns of vertebral artery compression, and favorable long-term outcome with conservative treatments. In most patients with RVAO, the symptoms may be ascribed to asymmetrical excitation of the bilateral labyrinth induced by transient ischemia or by disinhibition from inferior cerebellar hypoperfusion. Conservative management might be considered as the first-line treatment of RVAO.