bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Regional Influence of an Intense Sierra Barrier Jet and Landfalling Atmospheric River on Orographic Precipitation in Northern California: A Case Study
Authors: Neiman Paul J. , Ralph F. Martin , Moore Benjamin J. , Zamora Robert J. 
Published: April 2014

Abstract
A 915-MHz wind profiler, a GPS receiver, and surface meteorological sites in and near California’s northern Central Valley (CV) provide the observational anchor for a case study on 23–25 October 2010. The study highlights key orographic influences on precipitation distributions and intensities across northern California during a landfalling atmospheric river (AR) and an associated Sierra barrier jet (SBJ). A detailed wind profiler/GPS analysis documents an intense AR overriding a shallow SBJ at ~750 m MSL, resulting in record early season precipitation. The SBJ diverts shallow, pre-cold-frontal, incoming water vapor within the AR poleward from the San Francisco Bay gap to the northern CV. The SBJ ultimately decays following the passage of the AR and trailing polar cold front aloft. A statistical analysis of orographic forcing reveals that both the AR and SBJ are crucial factors in determining the amount and spatial distribution of precipitation in the northern Sierra Nevada and in the Shasta–Trinity region at the northern terminus of the CV. As the AR and SBJ flow ascends the steep and tall terrain of the northern Sierra and Shasta–Trinity region, respectively, the precipitation becomes enhanced. Vertical profiles of the linear correlation coefficient quantify the orographic linkage between hourly upslope water vapor flux profiles and hourly rain rate. The altitude of maximum correlation (i.e., orographic controlling layer) is lower for the shallow SBJ than for the deeper AR (i.e., 0.90 versus 1.15 km MSL, respectively). This case study expands the understanding of orographic precipitation enhancement from coastal California to its interior. It also quantifies the connection between dry antecedent soils and reduced flood potential.
Geostrophic Turbulence in the Frequency–Wavenumber Domain: Eddy-Driven Low-Frequency Variability*
Authors: Arbic Brian K. , Müller Malte , Richman James G. , Shriver Jay F. , Morten Andrew J. , Scott Robert B. , Sérazin Guillaume , Penduff Thierry 
Published: April 2014

Abstract
Motivated by the potential of oceanic mesoscale eddies to drive intrinsic low-frequency variability, this paper examines geostrophic turbulence in the frequency–wavenumber domain. Frequency–wavenumber spectra, spectral fluxes, and spectral transfers are computed from an idealized two-layer quasigeostrophic (QG) turbulence model, a realistic high-resolution global ocean general circulation model, and gridded satellite altimeter products. In the idealized QG model, energy in low wavenumbers, arising from nonlinear interactions via the well-known inverse cascade, is associated with energy in low frequencies and vice versa, although not in a simple way. The range of frequencies that are highly energized and engaged in nonlinear transfer is much greater than the range of highly energized and engaged wavenumbers. Low-frequency, low-wavenumber energy is maintained primarily by nonlinearities in the QG model, with forcing and friction playing important but secondary roles. In the high-resolution ocean model, nonlinearities also generally drive kinetic energy to low frequencies as well as to low wavenumbers. Implications for the maintenance of low-frequency oceanic variability are discussed. The cascade of surface kinetic energy to low frequencies that predominates in idealized and realistic models is seen in some regions of the gridded altimeter product, but not in others. Exercises conducted with the general circulation model suggest that the spatial and temporal filtering inherent in the construction of gridded satellite altimeter maps may contribute to the discrepancies between the direction of the frequency cascade in models versus gridded altimeter maps seen in some regions. Of course, another potential reason for the discrepancy is missing physics in the models utilized here.
Some Considerations for the Use of High-Resolution Mobile Radar Data in Tornado Intensity Determination
Authors: Snyder Jeffrey C. , Bluestein Howard B. 
Published: April 2014

Abstract
The increasing number of mobile Doppler radars used in field campaigns across the central United States has led to an increasing number of high-resolution radar datasets of strong tornadoes. There are more than a few instances in which the radar-measured radial velocities substantially exceed the estimated wind speeds associated with the enhanced Fujita (EF) scale rating assigned to a particular tornado. It is imperative, however, to understand what the radar data represent if one wants to compare radar observations to damage-based EF-scale estimates. A violent tornado observed by the rapid-scan, X-band, polarimetric mobile radar (RaXPol) on 31 May 2013 contained radar-relative radial velocities exceeding 135 m s−1 in rural areas essentially devoid of structures from which damage ratings can be made. This case, along with others, serves as an excellent example of some of the complications that arise when comparing radar-estimated velocities with the criteria established in the EF scale. In addition, it is shown that data from polarimetric radars should reduce the variance of radar-relative radial velocity estimates within the debris field compared to data from single-polarization radars. Polarimetric radars can also be used to retrieve differential velocity, large magnitudes of which are spatially associated with large spectrum widths inside the polarimetric tornado debris signature in several datasets of intense tornadoes sampled by RaXPol.
Knocking down CDK4 mediates the elevation of let-7c suppressing cell growth in nasopharyngeal carcinoma
Authors: Liu Zhen , Long Xiaobin , Chao Cheng , Yan Chen , Wu Qiangyun , Hua Shengni , Zhang Yajie , Wu Aibing , Fang Weiyi 
Published: April 2014

Abstract

Background
CDK4 is a protein kinase in the CDK family important for G1/S phase cell cycle progression. However, the roles and molecular mechanisms of CDK4 triggering nasopharynx carcinogenesis are still unclear.

Methods
Lentiviral-vector mediated shRNA was used to suppress CDK4 expression and examine its molecular mechanisms. Using immunohistochemistry, we analyzed CDK4 protein expression in clinicopathologically characterized nasopharyngeal carcinoma (NPC) cases and nasopharyngeal tissues (NPs). Survival curves were plotted by the Kaplan-Meier method and compared using the log-rank test.

Results
In this investigation, we knocked down CDK4 expression and observed that NPC cell growth and cell cycle progression were significantly blocked by suppressing expression of CCND1, CDK6, and E2F1 as well as elevated p21 expression. Further, we found that reduced CDK4 expression elevated the expression of let-7c, a tumor-suppressive miRNA modulated by E2F1. We found that let-7c was markedly downregulated in NPC tissues compared to NPs and suppressed cell growth and cell cycle progression by modulating p15/p16/CDK4/E2F1 pathway. Finally, CDK4 protein was observed to be overexpressed in NPC tissues and could be considered an unfavorable prognosis factor for NPC patients although its independent prognostic value did not reach statistical significance (p = 0.087).

Conclusions
Our results demonstrated that overexpressed CDK4 is an unfavorable prognostic factor which suppresses the expression of tumor suppressive-factor let-7c through p21/CCND1/CDK6/E2F1 signaling, and inhibits cell proliferation by p15/p16/CDK4/E2F1 feedback signaling in NPC.
Approaches to ascertaining comorbidity information: validation of routine hospital episode data with clinician-based case note review
Authors: Soo Martin , Robertson Lynn M , Ali Tariq , Clark Laura E , Fluck Nicholas , Johnston Marjorie , Marks Angharad , Prescott Gordon J , Smith William Cairns S , Black Corri 
Published: April 2014

AbstractBackgroundIn clinical practice, research, and increasingly health surveillance, planning and costing, there is a need for high quality information to determine comorbidity information about patients. Electronic, routinely collected healthcare data is capturing increasing amounts of clinical information as part of routine care. The aim of this study was to assess the validity of routine hospital administrative data to determine comorbidity, as compared with clinician-based case note review, in a large cohort of patients with chronic kidney disease.MethodsA validation study using record linkage. Routine hospital administrative data were compared with clinician-based case note review comorbidity data in a cohort of 3219 patients with chronic kidney disease. To assess agreement, we calculated prevalence, kappa statistic, sensitivity, specificity, positive predictive value and negative predictive value. Subgroup analyses were also performed.ResultsMedian age at index date was 76.3 years, 44% were male, 67% had stage 3 chronic kidney disease and 31% had at least three comorbidities. For most comorbidities, we found a higher prevalence recorded from case notes compared with administrative data. The best agreement was found for cerebrovascular disease (κ = 0.80) ischaemic heart disease (κ = 0.63) and diabetes (κ = 0.65). Hypertension, peripheral vascular disease and dementia showed only fair agreement (κ = 0.28, 0.39, 0.38 respectively) and smoking status was found to be poorly recorded in administrative data. The patterns of prevalence across subgroups were as expected and for most comorbidities, agreement between case note and administrative data was similar. Agreement was less, however, in older ages and for those with three or more comorbidities for some conditions.ConclusionsThis study demonstrates that hospital administrative comorbidity data compared moderately well with case note review data for cerebrovascular disease, ischaemic heart disease and diabetes, however there was significant under-recording of some other comorbid conditions, and particularly common risk factors.
Continuous endotracheal tube cuff pressure control system protects against ventilator-associated pneumonia
Authors: Lorente Leonardo , Lecuona María , Jiménez Alejandro , Lorenzo Lisset , Roca Isabel , Cabrera Judith , Llanos Celina , Mora María L 
Published: April 2014

Abstract
Introduction
The use of a system for continuous control of endotracheal tube cuff pressure reduced the incidence of ventilator-associated pneumonia (VAP) in one randomized controlled trial (RCT) with 112 patients but not in another RCT with 142 patients. In several guidelines on the prevention of VAP, the use of a system for continuous or intermittent control of endotracheal cuff pressure is not reviewed. The objective of this study was to compare the incidence of VAP in a large sample of patients (n = 284) treated with either continuous or intermittent control of endotracheal tube cuff pressure.

Methods
We performed a prospective observational study of patients undergoing mechanical ventilation during more than 48 hours in an intensive care unit (ICU) using either continuous or intermittent endotracheal tube cuff pressure control. Multivariate logistic regression analysis (MLRA) and Cox proportional hazard regression analysis were used to predict VAP. The magnitude of the effect was expressed as odds ratio (OR) or hazard ratio (HR), respectively, and 95% confidence interval (CI).

Results
We found a lower incidence of VAP with the continuous (n = 150) than with the intermittent (n = 134) pressure control system (22.0% versus 11.2%; p = 0.02). MLRA showed that the continuous pressure control system (OR = 0.45; 95% CI = 0.22-0.89; p = 0.02) and the use of an endotracheal tube incorporating a lumen for subglottic secretion drainage (SSD) (OR = 0.39; 95% CI = 0.19-0.84; p = 0.02) were protective factors against VAP. Cox regression analysis showed that the continuous pressure control system (HR = 0.45; 95% CI = 0.24-0.84; p = 0.01) and the use of an endotracheal tube incorporating a lumen for SSD (HR = 0.29; 95% CI = 0.15-0.56; p < 0.001) were protective factors against VAP. However, the interaction between type of endotracheal cuff pressure control system (continuous or intermittent) and endotracheal tube (with or without SSD) was not statistically significant in MLRA (OR = 0.41; 95% CI = 0.07-2.37; p = 0.32) or in Cox analysis (HR = 0.35; 95% CI = 0.06-1.84; p = 0.21).

Conclusions
The use of a continuous endotracheal cuff pressure control system and/or an endotracheal tube with a lumen for SSD could help to prevent VAP in patients requiring more than 48 hours of mechanical ventilation.
Should Event Organizers Prevent Resale of Tickets?
Authors: Cui Yao , Duenyas Izak , Şahin Özge 
Published: April 2014

We are interested in whether preventing resale of tickets benefits the capacity providers for sporting and entertainment events. Common wisdom suggests that ticket resale is harmful to event organizers' revenues, and event organizers have tried to prevent resale of tickets. For instance, Ticketmaster recently proposed paperless (nontransferrable) ticketing, which would severely limit the opportunity to resell tickets. We consider a model that allows resale from both consumers and speculators with different transaction costs for each party. Surprisingly, we find that this wisdom is incorrect when event organizers use fixed pricing policies; in fact, event organizers benefit from reductions in consumers' (and speculators') transaction costs of resale. Even when multiperiod pricing policies are used, we find that an event organizer may still benefit from ticket resale if his capacity is small. Although paperless ticketing is suggested as a way to reduce ticket resale and prevent speculators from buying tickets, our results suggest that it may reduce the capacity providers' revenues in many situations. Instead, we propose ticket options as a novel ticket pricing mechanism. We show that ticket options (where consumers would initially buy an option to buy a ticket and then exercise at a later date) naturally reduce ticket resale significantly and result in significant increases in event organizers' revenues. Furthermore, since a consumer only risks the option price (and not the whole ticket price) if she cannot attend the event, options may face less consumer resistance than paperless tickets. This paper was accepted by Serguei Netessine, operations management.
Childhood Pneumonia in Low and Middle Income Countries: Burden,
Prevention and Management
Authors: Gray D. , Zar H.J. 
Published: April 2014

Background:
Pneumonia is the leading cause of morbidity and mortality in children under five years of age
worldwide. The burden of childhood pneumonia occurs predominantly in low or middle income countries. Despite recent
advances in management and preventative strategies, high rates of treatment failure and case fatality continue to occur in
children in such countries.

Aim:
To review the current evidence on the epidemiology and management of childhood pneumonia in low and middle
income countries.

Methods:
Direct search of Medline database from 1995 to date through Pubmed was conducted. Search terms included:
(pneumonia OR lower respiratory tract infections OR lower respiratory infections OR ARI) AND child. Search was
restricted to English articles. In addition reference lists of selected studies were reviewed for relevant information.

Findings:
Major findings accounting for the high burden include delayed health seeking, poor access to health care,
poorly resourced health care systems, inadequate immunisation programs and lack of availability of oxygen delivery
systems. The burden of pneumonia deaths has also been increased by the paediatric HIV epidemic in sub-Saharan Africa.
Effective preventive interventions include exclusive breastfeeding, optimizing nutrition, reduction of indoor air pollution
and immunisations. Wider availability of new immunisations particularly pneumococcal conjugate vaccine can
substantially reduce pneumonia incidence. Prophylactic trimethoprim- sulphamethoxazole and antiretroviral therapy are
important strategies to prevent pneumonia in HIV infected children, and wider implementation of these is still needed.
The most effective treatment strategy remains case management guidelines as contained in the Integrated Management of
Childhood Illness program. Case management efficacy is dependent on timely access to health facilities, on health worker
ability to recognise and treat pneumonia or severe pneumonia and on availability of appropriate antibiotics and
functioning referral pathways. In areas of high HIV prevalence, guidelines must be adapted to broaden antimicrobial
coverage including treatment for Pneumocystis jirovecii pneumonia. Monitoring of hypoxia with pulse oximetry and
appropriate oxygen delivery systems are still not widely available and should be prioritized in pneumonia management
programs.

Conclusions:
Improved access to preventive and management strategies is urgently needed to reduce the burden of
childhood pneumonia in resource limited settings. Further research on childhood pneumonia is needed to delineate the
burden of specific pathogens, to develop better diagnostic tests and to improve current management and preventive
strategies.
Dose Optimisation: A Strategy to Improve Tolerability and Lower
Antiretroviral Drug Prices in Low and Middle Income Countries
Authors: Hill Andrew , Ananworanich Jinatanat , Calmy Alexandra 
Published: April 2014

Four million people have been initiated on antiretroviral treatment in low and middle income countries.
However, an additional 5 million people eligible for treatment are not receiving it. Of the 27-29 million people infected
with HIV but not currently receiving treatment, most will need to start antiretrovirals as their disease progresses. Funding
for access programmes is restricted, partly because of the Global Financial Crisis. Antiretroviral treatment programmes
have to lower overall costs, so that the maximum number of people with HIV can be treated for limited budgets.
Antiretroviral treatment can account for the majority of the total cost of access programmes.
During the development of antiretrovirals, several doses are normally evaluated in Phase 2 dose-ranging trials. In the case
of efavirenz, lopinavir/ritonavir and raltegravir, there was no difference in efficacy between doses evaluated at Phase 2,
but the higher doses were then taken into Phase 3 registration trials, leading to regulatory approval.
Re-analysis of the dose-ranging trials of raltegravir showed equal efficacy for doses in the range of 100 to 600mg twice
daily. The main Phase 2 trial of efavirenz, DMP-005, suggests that a 400mg once daily dose should show equal efficacy to
the standard 600mg once daily dose. The dose-ranging trials of lopinavir/ritonavir showed the highest efficacy at the
200/100mg mg twice daily dose, compared with the standard 400/100 mg twice daily dose.
Re-optimisation of doses could dramatically lower costs of first and second-line treatment for low and middle income
countries. For example, it may be possible to manufacture raltegravir 100 mg twice daily for US $75-100, allowing firstline
use in low income countries. Costs of efavirenz could be lowered by 30%, and lopinavir/ritonavir by 35%, using reoptimised
doses. There may also be safety benefits to these new doses.
Developmental Expression of Insulin Receptor Substrate-2 During Dimethylsulfoxide-Induced Differentiation of Human HL-60 Cells
Authors: Schacher Daniel H. , VanHoy Roger W. , Liu Qiang , Arkins Sean , Dantzer Robert , Freund Gregory G. , Kelley Keith W. 
Published: April 2014

AbstractInsulin receptor substrate-2 (IRS-2) is phosphorylated on tyrosine by a number of cytokine receptors and is implicated in the activation of phosphatidylinositol 3′-kinase (PI3-kinase). Here, we demonstrate that induction of granulocytic differentiation of human promyeloid HL-60 cells leads to an increase in the amount of IRS-2 that is phosphorylated in response to insulin-like growth factor (IGF)-I. Although PI3-kinase is often activated following interaction with IRS-1, we could not detect IRS-1 protein, IRS-1 mRNA, or IRS-1-precipitable PI3-kinase enzymatic activity. However, PI3-kinase activity that was coimmunoprecipitated with either anti-phosphotyrosine or anti-IRS-2 following IGF-I stimulation was increased 100-fold. Heightened tyrosine phosphorylation of IRS-2 during granulocytic differentiation was not caused by an increase in expression of the tyrosine kinase IGF-I receptor, as measured by the amount of both the α- and β-subunits. Instead, immunoblotting experiments with an Ab to IRS-2 revealed that induction of granulocytic differentiation caused a large increase in IRS-2, and this occurred in the absence of detectable IRS-1 protein. These IRS-2-positive cells could not differentiate into more mature myeloid cells in serum-free medium unless IGF-I was added. These data are consistent with a model of granulocytic differentiation that requires at least two signals, the first of which leads to an increase in the cytoplasmic pool of IRS-2 protein and a second molecule that acts to tyrosine phosphorylate IRS-2 and enhance granulocytic differentiation.
Deriving Quantitative Constraints on T Cell Selection from Data on the Mature T Cell Repertoire
Authors: Detours Vincent , Mehr Ramit , Perelson Alan S. 
Published: April 2014

AbstractThe T cell repertoire is shaped in the thymus through positive and negative selection. Thus, data about the mature repertoire may be used to infer information on how TCR generation and selection operate. Assuming that T cell selection is affinity driven, we derive the quantitative constraints that the parameters driving these processes must fulfill to account for the experimentally observed levels of alloreactivity, self MHC restriction and the frequency of cells recognizing a given foreign Ag. We find that affinity-driven selection is compatible with experimental estimates of these latter quantities only if 1) TCRs see more peptide residues than MHC polymorphic residues, 2) the majority of positively selected clones are deleted by negative selection, 3) between 1 and 3.6 clonal divisions occur on average in the thymus after completion of TCR rearrangement, and 4) selection is driven by 103–105 self peptides.
Effects of T3Rα1 and T3Rα2 Gene Deletion on T and B Lymphocyte Development
Authors: Arpin Christophe , Pihlgren Maria , Fraichard Alexandre , Aubert Denise , Samarut Jacques , Chassande Olivier , Marvel Jacqueline 
Published: April 2014

AbstractThyroid hormones bind to several nuclear receptors encoded by T3Rα and T3Rβ genes. There is now accumulating evidence that thyroid hormones act on the immune system. Indeed, mice deficient for thyroid hormones show a reduction in lymphocyte production. However, the mechanisms involved and, in particular, the role of the different thyroid hormone receptors in lymphocyte development have not been investigated. To address that question, we have studied lymphocyte development in mice deficient for the T3Rα1 and T3Rα2 gene products. A strong decrease in spleen cell numbers was found compared with wild-type littermates, B lymphocytes being more severely affected than T lymphocytes. A significant decrease in splenic macrophage and granulocyte numbers was also found. In bone marrow, a reduction in CD45+/IgM− pro/pre-B cell numbers was found in these mice compared with wild-type littermates. This decrease seems to result from a proliferation defect, as CD45+/IgM− cells incorporate less 5-bromo-2′-deoxyuridine in vivo. To define the origin of the bone marrow development defect, chimeric animals between T3Rα−/− and Rag1−/− mice were generated. Results indicate that for B cells the control of the population size by T3Rα1 and T3Rα2 is intrinsic. Altogether, these results show that T3Rα1 or T3Rα2 gene products are implicated in the control of the B cell pool size.