bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Cyanobacterial Photoreceptors Regulate Photosynthetic Light Harvesting by Sensing Teal, Green, Yellow, and Red Light
Authors: Wiltbank Lisa B. , Kehoe David M. 
Published: February 2016

ABSTRACTThe genomes of many photosynthetic and nonphotosynthetic bacteria encode numerous phytochrome superfamily photoreceptors whose functions and interactions are largely unknown. Cyanobacterial genomes encode particularly large numbers of phytochrome superfamily members called cyanobacteriochromes. These have diverse light color-sensing abilities, and their functions and interactions are just beginning to be understood. One of the best characterized of these functions is the regulation of photosynthetic light-harvesting antenna composition in the cyanobacteriumFremyella diplosiphonby the cyanobacteriochrome RcaE in response to red and green light, a process known as chromatic acclimation. We have identified a new cyanobacteriochrome named DpxA that maximally senses teal (absorption maximum, 494 nm) and yellow (absorption maximum, 568 nm) light and represses the accumulation of a key light-harvesting protein called phycoerythrin, which is also regulated by RcaE during chromatic acclimation. Like RcaE, DpxA is a two-component system kinase, although these two photoreceptors can influence phycoerythrin expression through different signaling pathways. The peak responsiveness of DpxA to teal and yellow light provides highly refined color discrimination in the green spectral region, which provides important wavelengths for photosynthetic light harvesting in cyanobacteria. These results redefine chromatic acclimation in cyanobacteria and demonstrate that cyanobacteriochromes can coordinately impart sophisticated light color sensing across the visible spectrum to regulate important photosynthetic acclimation processes.IMPORTANCEThe large number of cyanobacteriochrome photoreceptors encoded by cyanobacterial genomes suggests that these organisms are capable of extremely complex light color sensing and responsiveness, yet little is known about their functions and interactions. Our work uncovers previously undescribed cooperation between two photoreceptors with very different light color-sensing capabilities that coregulate an important photosynthetic light-harvesting protein in response to teal, green, yellow, and red light. Other cyanobacteriochromes that have been shown to interact functionally sense wavelengths of light that are close to each other, which makes it difficult to clearly identify their physiological roles in the cell. Our finding of two photoreceptors with broad light color-sensing capabilities and clearly defined physiological roles provides new insights into complex light color sensing and its regulation.
Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study
Authors: Rorie David A , Rogers Amy , Mackenzie Isla S , Ford Ian , Webb David J , Willams Bryan , Brown Morris , Poulter Neil , Findlay Evelyn , Saywood Wendy , MacDonald Thomas M 
Published: February 2016

IntroductionNocturnal blood pressure (BP) appears to be a better predictor of cardiovascular outcome than daytime BP. The BP lowering effects of most antihypertensive therapies are often greater in the first 12 h compared to the next 12 h. The Treatment In Morning versus Evening (TIME) study aims to establish whether evening dosing is more cardioprotective than morning dosing.Methods and analysisThe TIME study uses the prospective, randomised, open-label, blinded end-point (PROBE) design. TIME recruits participants by advertising in the community, from primary and secondary care, and from databases of consented patients in the UK. Participants must be aged over 18 years, prescribed at least one antihypertensive drug taken once a day, and have a valid email address. After the participants have self-enrolled and consented on the secure TIME website (http://www.timestudy.co.uk) they are randomised to take their antihypertensive medication in the morning or the evening. Participant follow-ups are conducted after 1 month and then every 3 months by automated email. The trial is expected to run for 5 years, randomising 10 269 participants, with average participant follow-up being 4 years. The primary end point is hospitalisation for the composite end point of non-fatal myocardial infarction (MI), non-fatal stroke (cerebrovascular accident; CVA) or any vascular death determined by record-linkage. Secondary end points are: each component of the primary end point, hospitalisation for non-fatal stroke, hospitalisation for non-fatal MI, cardiovascular death, all-cause mortality, hospitalisation or death from congestive heart failure. The primary outcome will be a comparison of time to first event comparing morning versus evening dosing using an intention-to-treat analysis. The sample size is calculated for a two-sided test to detect 20% superiority at 80% power.Ethics and disseminationTIME has ethical approval in the UK, and results will be published in a peer-reviewed journal.Trial registration numberUKCRN17071; Pre-results.
The Irish National Adverse Events Study (INAES): the frequency and nature of adverse events in Irish hospitals—a retrospective record review study
Authors: Rafter Natasha , Hickey Anne , Conroy Ronan M , Condell Sarah , O'Connor Paul , Vaughan David , Walsh Gillian , Williams David J 
Published: February 2016

IntroductionIrish healthcare has undergone extensive change recently with spending cuts and a focus on quality initiatives; however, little is known about adverse event occurrence.ObjectiveTo assess the frequency and nature of adverse events in Irish hospitals.Methods1574 (53% women, mean age 54 years) randomly selected adult inpatient admissions from a sample of eight hospitals, stratified by region and size, across the Republic of Ireland in 2009 were reviewed using two-stage (nurse review of patient charts, followed by physician review of triggered charts) retrospective chart review with electronic data capture. Results were weighted to reflect the sampling strategy. The impact on adverse event rate of differing application of international adverse event criteria was also examined.Results45% of charts were triggered. The prevalence of adverse events in admissions was 12.2% (95% CI 9.5% to 15.5%), with an incidence of 10.3 events per 100 admissions (95% CI 7.5 to 13.1). Over 70% of events were considered preventable. Two-thirds were rated as having a mild-to-moderate impact on the patient, 9.9% causing permanent impairment and 6.7% contributing to death. A mean of 6.1 added bed days was attributed to events, representing an expenditure of €5550 per event. The adverse event rate varied substantially (8.6%–17.0%) when applying different published adverse event eligibility criteria.ConclusionsThis first study of adverse events in Ireland reports similar rates to other countries. In a time of austerity, adverse events in adult inpatients were estimated to cost over €194 million. These results provide important baseline data on the adverse event burden and, alongside web-based chart review, provide an incentive and methodology to monitor future patient-safety initiatives.
Detection of an Immunogenic HERV-E Envelope with Selective Expression in Clear Cell Kidney Cancer
Authors: Cherkasova Elena , Scrivani Claire , Doh Susan , Weisman Quinn , Takahashi Yoshiyuki , Harashima Nanae , Yokoyama Hisayuki , Srinivasan Ramaprasad , Linehan W. Marston , Lerman Michael I. , Childs Richard W. 
Published: February 2016

Abstract
VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common form of kidney cancer, express transcripts derived from the novel human endogenous retrovirus HERV-E (named CT-RCC HERV-E). In this study, we define a transcript encoding the entire envelope gene of HERV-E as expressed selectively in ccRCC tumors, as distinct from normal kidney tissues or other tumor types. Sequence analysis of this envelope transcript revealed long open reading frames encoding putative surface and transmembrane envelope proteins. Retroviral envelopes are known to be capable of eliciting immunity in humans. Accordingly, we found that HLA-A*0201–restricted peptides predicted to be products of the CT-RCC HERV-E envelope transcript–stimulated CD8+ T cells, which could recognize HLA-A*0201–positive HERV-E–expressing kidney tumor cells. Overall, our results offer evidence of unique HERV-E envelope peptides presented on the surface of ccRCC cells, offering potentially useful tumor-restricted targets for T-cell–based immunotherapy of kidney cancer. Cancer Res; 76(8); 2177–85. ©2016 AACR.
Clinical Trial of Oral Nelfinavir before and during Radiation Therapy for Advanced Rectal Cancer
Authors: Hill Esme J. , Roberts Corran , Franklin Jamie M. , Enescu Monica , West Nicholas , MacGregor Thomas P. , Chu Kwun-Ye , Boyle Lucy , Blesing Claire , Wang Lai-Mun , Mukherjee Somnath , Anderson Ewan M. , Brown Gina , Dutton Susan , Love Sharon B. , Schnabel Julia A. , Quirke Phil , Muschel Ruth , McKenna William G. , Partridge Michael , Sharma Ricky A. 
Published: February 2016

Abstract
Purpose: Nelfinavir, a PI3K pathway inhibitor, is a radiosensitizer that increases tumor blood flow in preclinical models. We conducted an early-phase study to demonstrate the safety of nelfinavir combined with hypofractionated radiotherapy (RT) and to develop biomarkers of tumor perfusion and radiosensitization for this combinatorial approach.
Experimental Design: Ten patients with T3-4 N0-2 M1 rectal cancer received 7 days of oral nelfinavir (1,250 mg b.i.d.) and a further 7 days of nelfinavir during pelvic RT (25 Gy/5 fractions/7 days). Perfusion CT (p-CT) and DCE-MRI scans were performed pretreatment, after 7 days of nelfinavir and prior to the last fraction of RT. Biopsies taken pretreatment and 7 days after the last fraction of RT were analyzed for tumor cell density (TCD).
Results: There were 3 drug-related grade 3 adverse events: diarrhea, rash, and lymphopenia. On DCE-MRI, there was a mean 42% increase in median Ktrans, and a corresponding median 30% increase in mean blood flow on p-CT during RT in combination with nelfinavir. Median TCD decreased from 24.3% at baseline to 9.2% in biopsies taken 7 days after RT (P = 0.01). Overall, 5 of 9 evaluable patients exhibited good tumor regression on MRI assessed by tumor regression grade (mrTRG).
Conclusions: This is the first study to evaluate nelfinavir in combination with RT without concurrent chemotherapy. It has shown that nelfinavir-RT is well tolerated and is associated with increased blood flow to rectal tumors. The efficacy of nelfinavir-RT versus RT alone merits clinical evaluation, including measurement of tumor blood flow. Clin Cancer Res; 22(8); 1922–31. ©2016 AACR.
See related commentary by Meyn et al., p. 1834
Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity
Authors: Garofalo Mariangela , Iovine Barbara , Kuryk Lukasz , Capasso Cristian , Hirvinen Mari , Vitale Andrea , Yliperttula Marjo , Bevilacqua Maria Assunta , Cerullo Vincenzo 
Published: February 2016

Abstract
Oncolytic viruses are able to specifically replicate, infect, and kill only cancer cells. Their combination with chemotherapeutic drugs has shown promising results due to the synergistic action of virus and drugs; the combinatorial therapy is considered a potential clinically relevant approach for cancer. In this study, we optimized a strategy to absorb peptides on the viral capsid, based on electrostatic interaction, and used this strategy to deliver an active antitumor drug. We used L-carnosine, a naturally occurring histidine dipeptide with a significant antiproliferative activity. An ad hoc modified, positively charged L-carnosine was combined with the capsid of an oncolytic adenovirus to generate an electrostatic virus–carnosine complex. This complex showed enhanced antitumor efficacy in vitro and in vivo in different tumor models. In HCT-116 colorectal and A549 lung cancer cell lines, the complex showed higher transduction ratio and infectious titer compared with an uncoated oncolytic adenovirus. The in vivo efficacy of the complex was tested in lung and colon cancer xenograft models, showing a significant reduction in tumor growth. Importantly, we investigated the molecular mechanisms underlying the effects of complex on tumor growth reduction. We found that complex induces apoptosis in both cell lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in future studies also for delivery of other bioactive drugs. Mol Cancer Ther; 15(4); 651–60. ©2016 AACR.
Photopreventive Effect and Mechanism of AZD4547 and Curcumin C3 Complex on UVB-Induced Epidermal Hyperplasia
Authors: Khandelwal Alok R. , Rong Xiaohua , Moore-Medlin Tara , Ekshyyan Oleksandr , Abreo Fleurette , Gu Xin , Nathan Cherie-Ann O. 
Published: February 2016

Abstract
Aggressive cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common type of skin cancer in the United States due to high exposure to ultraviolet B (UVB) radiation. In our previous studies, Curcumin C3 complex (C3), a standardized preparation of three curcumonoids, delayed UVB-induced tumor incidence and inhibited multiplicity. Exposure to UVB activates mTOR and FGFR signaling that play a key role in skin tumorigenesis. The purpose of this study was to investigate the efficacy of C3 complex to afford protection against acute UVB-induced hyperproliferation by targeting the mTOR and FGFR signaling pathways. Pretreatment with C3 complex significantly inhibited UVB-induced FGF-2 induction, FGF-2–induced cell proliferation, progression and colony formation, mTORC1 and mTORC2 activation, and FGFR2 phosphorylation in the promotion-sensitive JB6 cells epithelial cells. Further, FGFR was critical for UVB-induced mTOR activation, suggesting an important role of FGFR2 in UVB-induced mTOR signaling. SKH-1 mice pretreated with C3 (15 mg/kg/b.w.) for 2 weeks followed by a single exposure to UVB (180 mj/cm2) significantly attenuated UVB-induced mTORC1, mTORC2, and FGFR2 activation. To further assess the role of FGFR in UVB-induced hyperproliferation, SKH-1 mice were pretreated with AZD4547 (5 mg/kg/b.w.); a selective pan-FGFR kinase inhibitor followed by single exposure to UVB (180 mj/cm2). AZD4547 significantly inhibited UVB-induced mTORC1 and mTORC2 activation, epidermal hyperplasia and hyperproliferation. Our studies underscore the importance of FGFR signaling in UVB-induced acute skin changes and the role of FGFR/mTOR signaling in mediating the effects of C3 complex in the pathogenesis of skin cancer. Cancer Prev Res; 9(4); 296–304. ©2016 AACR.
Sex- and Method-Specific Reference Values for Right Ventricular Strain by 2-Dimensional Speckle-Tracking Echocardiography
Authors: Muraru Denisa , Onciul Sebastian , Peluso Diletta , Soriani Nicola , Cucchini Umberto , Aruta Patrizia , Romeo Gabriella , Cavalli Giacomo , Iliceto Sabino , Badano Luigi P. 
Published: February 2016

Background—
Despite the fact that assessment of right ventricular longitudinal strain (RVLS) carries important implications for patient diagnosis, prognosis, and treatment, its implementation in clinical settings has been hampered by the limited reference values and the lack of uniformity in software, method, and definition used for measuring RVLS. Accordingly, this study was designed to establish (1) the reference values for RVLS by 2-dimensional speckle-tracking echocardiography; and (2) their relationship with demographic, hemodynamic, and cardiac factors.

Methods and Results—

In 276 healthy volunteers (55% women; age, 18–76 years), free wall and septum RVLS (6 segments) and free wall RVLS (3 segments) using both 6- and 3-segment regions of interest were obtained. Feasibility of 6-segment RVLS was 92%. Free wall RVLS from 3- versus 6-segment regions of interest had similar values, yet 6-segment region of interest was more feasible (86% versus 73%;
P
<0.001) and reproducible. Reference values (lower limits of normality) were as follows: 6-segment RVLS, −24.7±2.6% (−20.0%) for men and −26.7±3.1% (−20.3%) for women; 3-segment RVLS, −29.3±3.4% (−22.5%) for men and −31.6±4.0% (−23.3%) for women (
P
<0.001). Free wall RVLS was 5±2 strain units (%) larger in magnitude than 6-segment RVLS, 10±4% larger than septal RVLS, and 2±4% larger in women than in men (
P
<0.001). At multivariable analysis, age, sex, pulmonary systolic pressure, right atrial minimal volume, as well as right atrial and left ventricular longitudinal strain resulted as correlates of RVLS values.

Conclusions—
This is the largest study providing sex- and method-specific reference values for RVLS. Our data may foster the implementation of 2-dimensional speckle-tracking echocardiography–derived RV analysis in clinical practice.
The Role of the Dry Static Stability for the Recent Change in the Pacific Walker Circulation
Authors: Sohn Byung-Ju , Lee Sukyoung , Chung Eui-Seok , Song Hwan-Jin 
Published: February 2016

Abstract
There is an uncertainty in how the Pacific Walker circulation (PWC) will change in response to increased greenhouse gas (GHG) warming. On average, climate models predict that the PWC will weaken. Observational evidence is mixed, with some evidence supporting the models while others do not. In this study, insight into the PWC trend is provided by examining the tropical dry static stability, a quantity that is inversely proportional to the strength of the PWC. For the 1979–2012 period, the static stability increased markedly in all phase 5 of the Coupled Model Intercomparison Project (CMIP5) models, far more so than in the satellite and global reanalysis data, which show a strengthening of the PWC. The stabilization is greater for a subset of models that simulate a significant weakening of the PWC.
With the observed sea surface temperature as the lower boundary condition, over the western tropical Pacific, atmospheric models that belong to the weakening-PWC-CMIP5 group produce greater stabilization than those that belong to the strengthening-PWC-CMIP5 group. Compared with the latter group, the former group of atmospheric models simulates weaker trade winds over the western and central tropical Pacific and, consistent with the Bjerknes mechanism, the corresponding CMIP5 models produce a weaker west–east gradient in tropical SST. Given that the models’ convective parameterizations overstabilize the atmosphere compared with an explicit convection, the findings here suggest that the models’ representations of tropical convection and stability contribute to the models’ tendency to simulate a weakening of the PWC and an El Niño–like SST.
On the Detection of Robust Multidecadal Changes in Earth’s Outgoing Longwave Radiation Spectrum
Authors: Bantges R. J. , Brindley H. E. , Chen X. H. , Huang X. L. , Harries J. E. , Murray J. E. 
Published: February 2016

Abstract
Differences between Earth’s global mean all-sky outgoing longwave radiation spectrum as observed in 1970 [Interferometric Infrared Spectrometer (IRIS)], 1997 [Interferometric Monitor for Greenhouse Gases (IMG)], and 2012 [Infrared Atmospheric Sounding Instrument (IASI)] are presented. These differences are evaluated to determine whether these are robust signals of multidecadal radiative forcing and hence whether there is the potential for evaluating feedback-type responses. IASI–IRIS differences range from +2 K in the atmospheric window (800–1000 cm−1) to −5.5 K in the 1304 cm−1 CH4 band center. Corresponding IASI–IMG differences are much smaller, at 0.2 and −0.8 K, respectively. More noticeably, IASI–IRIS differences show a distinct step change across the 1042 cm−1 O3 band that is not seen in IASI–IMG comparisons. This step change is a consequence of a difference in behavior when moving from colder to warmer scenes in the IRIS data compared to IASI and IMG. Matched simulations for the relevant periods using ERA reanalyses mimic the spectral behavior shown by IASI and IMG rather than by IRIS. These findings suggest that uncertainties in the spectral response of IRIS preclude the use of these data for quantitative assessments of forcing and feedback processes.
Precipitation Deficit Flash Droughts over the United States
Authors: Mo Kingtse C. , Lettenmaier Dennis P. 
Published: February 2016

AbstractFlash drought refers to relatively short periods of warm surface temperature and anomalously low and rapid decreasing soil moisture (SM). Based on the physical mechanisms associated with flash droughts, these events are classified into two categories: heat wave and precipitation P deficit flash droughts. In previous work, the authors have defined heat wave flash droughts as resulting from the confluence of severe warm air temperature Tair, which increases evapotranspiration (ET), and anomalously low and decreasing SM. Here, a second type of flash drought caused by precipitation deficits is explored. The authors term these events P-deficit flash droughts, which they associate with lack of P. Precipitation deficits cause ET to decrease and temperature to increase. The P-deficit flash droughts are analyzed based on observations of P, Tair, and SM and ET reconstructed using land surface models for the period 1916–2013. The authors find that P-deficit flash droughts are more common than heat wave flash droughts. They are about twice as likely to occur as heat wave flash droughts over the conterminous United States. They are most prevalent over the southern United States with maxima over the southern Great Plains and the Southwest, in contrast to heat wave flash droughts that are mostly likely to occur over the Midwest and the Pacific Northwest, where the vegetation cover is dense.
Review of Underwater Cable Shape Detection
Authors: Xu Chunying , Chen Jiawang , Yan Dongxu , Ji Jian 
Published: February 2016

AbstractUnderwater cables play vital roles in marine engineering because they provide power and communication connections from the shore to an increasing number of sea installations. To ensure the system is operating reliably and continuously, it is necessary to detect the shapes of underwater cables in real time. However, this task is difficult to accomplish because the underwater cables are located in a dynamic and complicated subsea environment, which can cause changes in position, depth, and visibility.In this report, the current development of underwater cable shape detection methods, including visual, acoustic, magnetic detection, and multisensor fusion detection, and the advantages and disadvantages are described and analyzed. Furthermore, the disadvantages of these methods are addressed, which, based on survey platforms with high cost, include a long detection period and the failure to reveal emergencies. Then, the need to construct a simple and reliable system to detect the shapes of underwater cables is highlighted, and one possible solution based on bend sensors embedded in underwater cables is discussed.