bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ugp and PitA Participate in the Selection of PHO-Constitutive Mutants
Authors: Iglesias Neves Henrique , Pereira Tuanny Fernanda , Yagil Ezra , Spira Beny 
Published: February 2015

ABSTRACT

Mutations that cause the constitutive expression of the PHO regulon of
Escherichia coli
occur either in the
pst
operon or in the
phoR
gene, which encode, respectively, a high-affinity P
i
transport system and a histidine kinase sensor protein. These mutations are normally selected on glycerol-2-phosphate (G2P) as the carbon source in the presence of excess P
i
. The emergence of early PHO-constitutive mutants, which appear after growth for up to 48 h on selective medium, depends on the presence of
phoA
, which codes for a periplasmic alkaline phosphatase, while late mutants, which appear after 48 h, depend both on
phoA
and on the
ugp
operon, which encodes a glycerophosphodiester transport system. The emergence of the late mutants hints at an adaptive mutation process. PHO-constitutive
phoR
mutants appear only in a host that is mutated in
pitA
, which encodes an alternative P
i
transport system that does not belong to the PHO regulon. The conserved Thr
217
residue in the PhoR protein is essential for PHO repression.

IMPORTANCE
One of the principal ways in which bacteria adapt to new nutrient sources is by acquiring mutations in key regulatory genes. The inability of
E. coli
to grow on G2P as a carbon source is used to select mutations that derepress the PHO regulon, a system of genes involved in the uptake of phosphorus-containing molecules. Mutations in the
pst
operon or in
phoR
result in the constitutive expression of the entire PHO regulon, including alkaline phosphatase, which hydrolyzes G2P. Here we demonstrate that the
ugp
operon, another member of the PHO regulon, is important for the selection of PHO-constitutive mutants under prolonged nutritional stress and that
phoR
mutations can be selected only in bacteria lacking
pitA
, which encodes a secondary P
i
transport system.
Injuries in World Cup telemark skiing: a 5-year cohort study
Authors: Johansen Melissa Woll , Steenstrup Sophie E , Bere Tone , Bahr Roald , Nordsletten Lars 
Published: February 2015

BackgroundThere are limited data on injuries in World Cup (WC) telemark skiing.ObjectiveTo describe the injury incidence and injury pattern seen among WC telemark skiers during the competitive season.MethodsWe interviewed all WC athletes (or their coach, if the athlete was not present) at the end of five winter seasons from 2008 until 2013. All acute injuries occurring in the competitive season that required the attention of medical personnel were registered. Exposure was calculated based on the official International Ski Federation (FIS) results database.Results149 acute injuries were registered during 565 WC skier seasons. The absolute injury incidence was 26.4 injuries per 100 athletes per season (95% CI 22.1 to 30.6), higher for females than males (risk ratio (RR) 1.49, 95% CI 1.07 to 2.08). During the FIS WC competitions, 69 injuries were registered, corresponding to a relative incidence of 8.2 injuries per 1000 runs (95% CI 6.3 to 10.1). The most frequently injured body part was the knee (21%) followed by the hand-finger-thumb (20%), ankle (13%) and shoulder/clavicle (13%). The absolute risk of knee and shoulder/clavicle injuries was higher for females versus males (RR for knee injuries 2.72, 95% CI 1.35 to 5.51; RR for shoulder/clavicle injuries 2.55, 95% CI 1.06 to 6.14). No differences were detected in the injury incidence between disciplines.ConclusionsFemale telemark skiers are at 1.5 times greater risk of injury than male skiers. The most commonly injured body part was the knee. The risk of knee and shoulder/clavicle injuries was higher for female athletes than for male athletes.
Association between sense of coherence in adolescence and social benefits later in life: a 12-year follow-up study
Authors: Würtz Else Toft , Fonager Kirsten , Mortensen Jens Tølbøll 
Published: February 2015

ObjectivesLocal government concerns over expenditure on social and healthcare are growing. The aim of the present study was to explore the association between a weak ‘sense of coherence’ (SOC) in teens and their subsequent risk of receiving social and healthcare benefits during young adulthood, and to monitor how SOC developed during this period.DesignProspective cohort study.SettingNorth Denmark Region.Participants773 Pupils from seventh and eighth forms who answered a questionnaire in 1998.Outcome measuresDifferent social benefits (from the Danish DREAM database embracing disbursed public social benefits). Change in SOC score from 1998 to 2010.Results722 had answered seven items of the original SOC-13 questionnaire (denoted by SOC-7). Girls with a weak SOC-7 (the lowest 1st quartile) in 1998 had a significantly increased risk of receiving unemployment benefits (RR 1.3 (1.1 to 1.6)), social assistance (RR 1.8 (1.3 to 2.5)) and sickness benefits (RR 1.5 (1.2 to 2.0)) compared with girls with a strong SOC-7. For boys, only minor protective and non-significant differences were found. The SOC answers from 1998 and 2010 were compared (n=394). SOC increased significantly and mostly in girls.ConclusionsSOC-7 may serve as a predictor for social life event outcomes and hence facilitate an early identification and a selective approach to support teenage girls with a weak SOC. From adolescence to young adulthood, SOC-7 was of a relatively unstable nature.
Sleep and use of electronic devices in adolescence: results from a large population-based study
Authors: Hysing Mari , Pallesen Ståle , Stormark Kjell Morten , Jakobsen Reidar , Lundervold Astri J , Sivertsen Børge 
Published: February 2015

ObjectivesAdolescents spend increasingly more time on electronic devices, and sleep deficiency rising in adolescents constitutes a major public health concern. The aim of the present study was to investigate daytime screen use and use of electronic devices before bedtime in relation to sleep.DesignA large cross-sectional population-based survey study from 2012, the youth@hordaland study, in Hordaland County in Norway.SettingCross-sectional general community-based study.Participants9846 adolescents from three age cohorts aged 16–19. The main independent variables were type and frequency of electronic devices at bedtime and hours of screen-time during leisure time.OutcomesSleep variables calculated based on self-report including bedtime, rise time, time in bed, sleep duration, sleep onset latency and wake after sleep onset.ResultsAdolescents spent a large amount of time during the day and at bedtime using electronic devices. Daytime and bedtime use of electronic devices were both related to sleep measures, with an increased risk of short sleep duration, long sleep onset latency and increased sleep deficiency. A dose–response relationship emerged between sleep duration and use of electronic devices, exemplified by the association between PC use and risk of less than 5 h of sleep (OR=2.70, 95% CI 2.14 to 3.39), and comparable lower odds for 7–8 h of sleep (OR=1.64, 95% CI 1.38 to 1.96).ConclusionsUse of electronic devices is frequent in adolescence, during the day as well as at bedtime. The results demonstrate a negative relation between use of technology and sleep, suggesting that recommendations on healthy media use could include restrictions on electronic devices.
Cohort differences in the levels and trajectories of frailty among older people in England
Authors: Marshall Alan , Nazroo James , Tampubolon Gindo , Vanhoutte Bram 
Published: February 2015

BackgroundThe level of frailty in the older population across age cohorts and how this changes is a factor in determining future care costs and may also influence the extent of socioeconomic and gender inequalities in frailty.MethodsWe model cohort-specific trajectories in frailty among the community dwelling population older than 50 years, using five waves (2002–2010) of the English Longitudinal Study of Ageing. We stratify our analysis by wealth and gender and use a frailty index, based on accumulation of ‘deficits’.ResultsFor males and females between the ages of 50 and 70 in 2002, frailty trajectories for adjacent age cohorts converge. However, levels of frailty are higher in recent compared with earlier cohorts at the older ages (for cohorts aged over 70 in 2002). These cohort differences are largest in the poorest wealth group, while for the most affluent, frailty trajectories overlap across all adjacent cohorts suggesting no change across cohorts.ConclusionsA key driver of the cohort differences in frailty that we observe is likely to be increased survival of frail individuals. Importantly, this paper illustrates that the social conditions experienced across the wealth distribution impacts on the rate of deficit accumulation in older populations. Our results on trajectories of frailty between 2002 and 2010 are pessimistic and, in the context of rising life expectancies, suggest that poorer older people in particular spend additional years of life in a frail state.
Trapping of buoyant fluids in fault-bound structures
Authors: Yielding Graham 
Published: February 2015

Abstract

Structural traps comprise surfaces having high capillary threshold pressure for fluid phases such as hydrocarbon or CO
2
. Traps may include top-seal, bottom-seal and side-seal surfaces, the latter commonly being faults. Faults may form seals by juxtaposition or by fault-rock. The first step in fault characterization is mapping the distribution of offset layers at the fault surface. This pattern (‘Allan diagram’) comprises the separation polygons. These same lines define the displacement distribution on the fault, and so can also be used as a quality-check of the interpretation. They are also a fundamental part of horizon maps. Despite their central role in subsurface mapping, construction of fault polygons remains a weak step in the workflow in many E&P companies. To characterize fault-rock effects, it is usual to consider an upscaled proxy such as shale gouge ratio (SGR), with the assumption that high SGR represents clay smears and low SGR represents clay-poor fault rock. Suitable estimates of hydraulic properties can then be applied to different parts of the fault surface. The property distribution on the fault side-seals allows an estimate of the maximum hydrocarbon column height that the trap might contain, by comparing the multiple potential leak-points and finding which predicts the shallowest contact.
What's the best way to teach computer science to beginners?
Authors: Guzdial Mark 
Published: February 2015

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm
Mark Guzdial questions the practice of teaching programming to new CS students by having them practice programming largely on their own.
MPEG column
Authors: Timmerer Christian 
Published: February 2015

The 110th MPEG meeting was held at the Strasbourg Convention and Conference Centre featuring the following highlights:
• The future of video coding standardization
• Workshop on media synchronization
• Standards at FDIS: Green Metadata and CDVS
• What's happening in MPEG-DASH?
Additional details about MPEG's 110th meeting can be also found here including the official press release and all publicly available documents.
Reprogramming of the ERRα and ERα Target Gene Landscape Triggers Tamoxifen Resistance in Breast Cancer
Authors: Thewes Verena , Simon Ronald , Schroeter Petra , Schlotter Magdalena , Anzeneder Tobias , Büttner Reinhard , Benes Vladimir , Sauter Guido , Burwinkel Barbara , Nicholson Robert I. , Sinn Hans-Peter , Schneeweiss Andreas , Deuschle Ulrich , Zapatka Marc , Heck Stefanie , Lichter Peter 
Published: February 2015

Abstract
Endocrine treatment regimens for breast cancer that target the estrogen receptor-α (ERα) are effective, but acquired resistance remains a limiting drawback. One mechanism of acquired resistance that has been hypothesized is functional substitution of the orphan receptor estrogen-related receptor-α (ERRα) for ERα. To examine this hypothesis, we analyzed ERRα and ERα in recurrent tamoxifen-resistant breast tumors and conducted a genome-wide target gene profiling analysis of MCF-7 breast cancer cell populations that were sensitive or resistant to tamoxifen treatment. This analysis uncovered a global redirection in the target genes controlled by ERα, ERRα, and their coactivator AIB1, defining a novel set of target genes in tamoxifen-resistant cells. Beyond differences in the ERα and ERRα target gene repertoires, both factors were engaged in similar pathobiologic processes relevant to acquired resistance. Functional analyses confirmed a requirement for ERRα in tamoxifen- and fulvestrant-resistant MCF-7 cells, with pharmacologic inhibition of ERRα sufficient to partly restore sensitivity to antiestrogens. In clinical specimens (n = 1041), increased expression of ERRα was associated with enhanced proliferation and aggressive disease parameters, including increased levels of p53 in ERα-positive cases. In addition, increased ERRα expression was linked to reduced overall survival in independent tamoxifen-treated patient cohorts. Taken together, our results suggest that ERα and ERRα cooperate to promote endocrine resistance, and they provide a rationale for the exploration of ERRα as a candidate drug target to treat endocrine-resistant breast cancer. Cancer Res; 75(4); 720–31. ©2015 AACR.
Cytidine Deaminase Axis Modulated by miR-484 Differentially Regulates Cell Proliferation and Chemoresistance in Breast Cancer
Authors: Ye Fu-Gui , Song Chuan-Gui , Cao Zhi-Gang , Xia Chen , Chen Dan-Na , Chen Li , Li Shan , Qiao Feng , Ling Hong , Yao Ling , Hu Xin , Shao Zhi-Ming 
Published: February 2015

Abstract
There has been little study of how the evolution of chemoresistance in cancer affects other aspects of disease pathogenesis. Here, we show that an important chemoresistance axis driven by cytidine deaminase (CDA) also acts to suppress cell-cycle progression by regulating cyclin E–CDK2 signaling. We found that CDA was regulated by miR-484 in a gemcitabine-resistant model of breast cancer. Elevating miR-484 expression reversed the CDA effects, thereby enhancing gemcitabine sensitivity, accelerating cell proliferation, and redistributing cell-cycle progression. Conversely, elevating CDA to restore its expression counteracted the chemosensitization and cell proliferative effects of miR-484. In clinical specimens of breast cancer, CDA expression was frequently downregulated and inversely correlated with miR-484 expression. Moreover, high expression of CDA was associated with prolonged disease-free survival in studied cohorts. Collectively, our findings established that miR-484–modulated CDA has a dual impact in promoting chemoresistance and suppressing cell proliferation in breast cancer, illustrating the pathogenic tradeoffs associated with the evolution of chemoresistance in this malignant disease. Cancer Res; 75(7); 1504–15. ©2015 AACR.
The Yin and Yang of Alloreactivity: Chronic Graft-versus-Host Disease and Leukemia Relapse
Authors: Gill Saar 
Published: February 2015

Abstract
Chronic graft-versus-host disease is a frequent complication of allogeneic hematopoietic cell transplantation and plays an important role in posttransplant morbidity and mortality, yet is correlated with the graft-versus-tumor effect in some studies. New approaches to separate the graft-versus-tumor from the graft-versus-host effect are urgently needed. Clin Cancer Res; 21(9); 1981–3. ©2015 AACR.
See related article by Boyiadzis et al., p. 2020
Can Circulating Tumor Cells Predict Resistance in Metastatic Breast Cancer?
Authors: Mathew Aju , Brufsky Adam M. , Davidson Nancy E. 
Published: February 2015

Abstract
Circulating tumor cell (CTC) enumeration provides prognostic but not predictive information for chemotherapy in metastatic breast cancer. Because CTC measurement is reproducible and allows molecular profiling, an assay to assess endocrine resistance was developed. Whether this CTC-based assay can be used to reliably select endocrine therapy must be tested. Clin Cancer Res; 21(11); 2421–3. ©2015 AACR.
See related article by Paoletti et al., p. 2487
Enhanced Antitumor Activity of 3-Bromopyruvate in Combination with Rapamycin In Vivo and In Vitro
Authors: Zhang Qi , Pan Jing , Lubet Ronald A. , Komas Steven M. , Kalyanaraman Balaraman , Wang Yian , You Ming 
Published: February 2015

Abstract
3-Bromopyruvate (3-BrPA) is an alkylating agent and a well-known inhibitor of energy metabolism. Rapamycin is an inhibitor of the serine/threonine protein kinase mTOR. Both 3-BrPA and rapamycin show chemopreventive efficacy in mouse models of lung cancer. Aerosol delivery of therapeutic drugs for lung cancer has been reported to be an effective route of delivery with little systemic distribution in humans. In this study, 3-BrPA and rapamycin were evaluated in combination for their preventive effects against lung cancer in mice by aerosol treatment, revealing a synergistic ability as measured by tumor multiplicity and tumor load compared treatment with either single-agent alone. No evidence of liver toxicity was detected by monitoring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes. To understand the mechanism in vitro experiments were performed using human non–small cell lung cancer (NSCLC) cell lines. 3-BrPA and rapamycin also synergistically inhibited cell proliferation. Rapamycin alone blocked the mTOR signaling pathway, whereas 3-BrPA did not potentiate this effect. Given the known role of 3-BrPA as an inhibitor of glycolysis, we investigated mitochondrial bioenergetics changes in vitro in 3-BrPA–treated NSCLC cells. 3-BrPA significantly decreased glycolytic activity, which may be due to adenosine triphosphate (ATP) depletion and decreased expression of GAPDH. Our results demonstrate that rapamycin enhanced the antitumor efficacy of 3-BrPA, and that dual inhibition of mTOR signaling and glycolysis may be an effective therapeutic strategy for lung cancer chemoprevention. Cancer Prev Res; 8(4); 318–26. ©2015 AACR.
Therapeutic Insights from Genomic Studies of Head and Neck Squamous Cell Carcinomas
Authors: Hammerman Peter S. , Hayes D. Neil , Grandis Jennifer R. 
Published: February 2015

Abstract
Summary: Large and comprehensive genomic surveys of head and neck squamous cell carcinomas (HNSCC) are now greatly increasing our understanding of the diversity of this disease and the key genomic changes that drive these tumors. The results from these studies are beginning to inform the introduction of novel therapies for patients with HNSCCs. Here, we review some of the key findings from recent genomic studies of head and neck cancers, including the most comprehensive study to date from The Cancer Genome Atlas Network. Cancer Discov; 5(3); 239–44. ©2015 AACR.
Age-Related Difference in the Sleep Pressure-Lowering Effect Between an Angiotensin II Receptor Blocker and a Calcium Channel Blocker in Asian Hypertensives
Authors: Kario Kazuomi , Hoshide Satoshi 
Published: February 2015

Sleep blood pressure (BP), which is partly determined by salt sensitivity and intake, is an important cardiovascular risk in hypertensives. However, there have been no studies on age-related differences in the sleep BP–lowering effect between angiotensin II receptor blockers and calcium channel blockers in Asians. Azilsartan Circadian and Sleep Pressure—the 1st Study was a multicenter, randomized, open-label, 2-parallel-group study conducted to compare the efficacy of 8-week oral treatment with an angiotensin II receptor blocker (azilsartan 20 mg) or a calcium channel blocker (amlodipine 5 mg) on sleep BP as evaluated by ambulatory BP monitoring. Among the overall population, amlodipine treatment achieved significantly greater reduction in sleep BP, awake BP, and 24-hour BP than azilsartan treatment. BP reduction by amlodipine was particularly pronounced in elderly hypertensive patients aged ≥60 years old. Among patients ≥60 years old, the amlodipine group had numerically, but not significantly, higher control rate of sleep BP compared with the azilsartan group. Similar results were found for awake BP and 24-hour BP. These results suggest a greater BP reduction/control by amlodipine compared with azilsartan and that reduction/control of BP by amlodipine was also more effective in the elderly population. As recommended in the American Society of Hypertension/The international Society of Hypertension and the National Institute for Health and Clinical Excellence guidelines for differentiating treatment according to age, amlodipine should be one of the options for starting treatment in the elderly population.

Clinical Trial URL—

http://clinicaltrials.gov/show/NCT01762501

Clinical Trial ID—
NCT01762501
Computing an Average When Part of the Population Is Not Perceived
Authors: Pavlovskaya Marina , Soroker Nachum , Bonneh Yoram S. , Hochstein Shaul 
Published: February 2015

AbstractThe syndrome of unilateral spatial neglect (USN) after right-hemisphere damage is characterized by failure of salient left-sided stimuli to activate an orienting response, attract attention, and gain access to conscious awareness. The explicit failure processing left-sided visual information is not uniform, however, and patients seem to be more successful performing certain visual tasks than others. The source of this difference is still not clear. We focus on processing of visual scene statistical properties, asking whether, in computing the average size of an array of objects, USN patients give appropriate weight to objects on the left; disregard left-side objects entirely; or assign them an intermediate, lower weight, in accord with their tendency to neglect these objects. The interest in testing this question stems from a series of studies in healthy individuals that led Chong and Treisman [Chong, S. C., & Treisman, A. Statistical processing: Computing the average size in perceptual groups. Vision Research, 45, 891–900, 2005a; Chong, S. C., & Treisman, A. Attentional spread in the statistical processing of visual displays. Perception & Psychophysics, 67, 1–13, 2005b] to propose that processing of statistical properties (like the average size of visual scene elements) is carried out in parallel, with no need for serial allocation of focal attention to the different scene elements. Our results corroborate this suggestion, showing that objects in the left (“neglected”) hemispace contribute to average size computation, despite a marked imbalance in spatial distribution of attention, which leads to a reduced weight of left-side elements in the averaging computation. This finding sheds light on the nature of the impairment in USN and on basic mechanisms underlying statistical processing in vision. We confirm that statistical processing depends mainly on spread-attention mechanisms, which are largely spared in USN.