bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simplifying Inclusion–Exclusion Formulas
Authors: GOAOC XAVIER , MATOUŠEK JIŘÍ , PATÁK PAVEL , SAFERNOVÁ ZUZANA , TANCER MARTIN 
Published: October 2014

Let $\mathcal{F}$ = {F1, F2,. . ., Fn} be a family of n sets on a ground set S, such as a family of balls in ℝd. For every finite measure μ on S, such that the sets of $\mathcal{F}$ are measurable, the classical inclusion–exclusion formula asserts that
$\[\mu(F_1\cup F_2\cup\cdots\cup F_n)=\sum_{I:\emptyset\ne I\subseteq[n]} (-1)^{|I|+1}\mu\biggl(\bigcap_{i\in I} F_i\biggr),\]$
that is, the measure of the union is expressed using measures of various intersections. The number of terms in this formula is exponential in n, and a significant amount of research, originating in applied areas, has been devoted to constructing simpler formulas for particular families $\mathcal{F}$. We provide an upper bound valid for an arbitrary $\mathcal{F}$: we show that every system $\mathcal{F}$ of n sets with m non-empty fields in the Venn diagram admits an inclusion–exclusion formula with mO(log2n) terms and with ±1 coefficients, and that such a formula can be computed in mO(log2n) expected time. For every ϵ > 0 we also construct systems with Venn diagram of size m for which every valid inclusion–exclusion formula has the sum of absolute values of the coefficients at least Ω(m2−ϵ).
THE BEST WEIGHTED GRADIENT APPROXIMATION TO AN OBSERVED FUNCTION
Authors: HOWLETT PHIL 
Published: October 2014

AbstractWe find the potential function whose gradient best approximates an observed square integrable function on a bounded open set subject to prescribed weight factors. With an appropriate choice of topology, we show that the gradient operator is a bounded linear operator and that the desired potential function is obtained by solving a second-order, self-adjoint, linear, elliptic partial differential equation. The main result makes a precise analogy with a standard procedure for the best approximate solution of a system of linear algebraic equations. The use of bounded operators means that the definitive equation is expressed in terms of well-defined functions and that the error in a numerical solution can be calculated by direct substitution into this equation. The proposed method is illustrated with a hypothetical example.
The routine use of the Edmonton Classification System for Cancer Pain in an outpatient supportive care center
Authors: Arthur Joseph , Yennurajalingam Sriram , Nguyen Linh , Tanco Kimberson , Chisholm Gary , Hui David , Bruera Eduardo 
Published: October 2014

AbstractObjective:There is no standardized and universally accepted pain classification system for the assessment and management of cancer pain in both clinical practice and research studies. The Edmonton Classification System for Cancer Pain (ECS–CP) is an assessment tool that has demonstrated value in assessing pain characteristics and response. The purpose of our study was to determine the relationship between negative ECS–CP features and some pain-related variables like pain intensity and opioid use. We also explored whether the number of negative ECS–CP features was associated with higher pain intensity.Method:The electronic charts of 100 patients at an outpatient supportive care clinic in a comprehensive cancer center were reviewed for variables like patient characteristics, initial ECS–CP assessment, morphine equivalent daily dose (MEDD), opioid rotation, Edmonton Symptom Assessment Score (ESAS), and use of adjuvant analgesics.Results:Some 91 of the 100 charts were eligible for analysis. The most common primary cancer type was gastrointestinal (22.1%). The median pain intensity was 6, and the median MEDD was 45 mg. Neuropathic pain was associated with higher median pain intensity (7 vs. 5, p = 0.007) and median MEDD requirement (83 vs. 30, p = 0.013). Psychological distress was associated with higher median pain intensity (7 vs. 5, p = 0.042). Incident pain was also associated with a trend toward higher pain intensity (6 vs. 5, p = 0.06). A higher number of negative ECS–CP features was associated with higher pain intensity (p = 0.01).Significance of Results:The ECS–CP was successfully completed in the majority of patients, demonstrating its utility in routine clinical practice. Neuropathic pain and psychological distress were associated with higher pain intensity. Also, neuropathic pain was associated with a higher MEDD. A higher sum of negative ECS–CP features was associated with higher pain intensity. Further studies will be needed to verify and explore these observations.
Blurring the boundaries between public and private health care services as an alternative explanation for the emergence of black medicine: the Israeli case
Authors: Filc Dani , Cohen Nissim 
Published: October 2014

AbstractBlack medicine represents the most problematic configuration of informal payments for health care. According to the accepted economic explanations, we would not expect to find black medicine in a system with a developed private service. Using Israel as a case study, we suggest an alternative yet a complimentary explanation for the emergence of black medicine in public health care systems – even though citizens do have the formal option to use private channels. We claim that when regulation is weak and political culture is based on ‘do it yourself’ strategies, which meant to solve immediate problems, blurring the boundaries between public and private health care services may only reduce public trust and in turn, contribute to the emergence of black medicine. We used a combined quantitative and qualitative methodology to support our claim. Statistical analysis of the results suggested that the only variable significantly associated with the use of black medicine was trust in the health care system. The higher the respondents’ level of trust in the health care system, the lower the rate of the use of black medicine. Qualitatively, interviewee emphasized the relation between the blurred boundaries between public and private health care and the use of black medicine.
Optical control of insulin release using a photoswitchable sulfonylurea
Authors: Broichhagen Johannes , Schönberger Matthias , Cork Simon C. , Frank James A. , Marchetti Piero , Bugliani Marco , Shapiro A. M. James , Trapp Stefan , Rutter Guy A. , Hodson David J. , Trauner Dirk 
Published: October 2014

AbstractSulfonylureas are widely prescribed for the treatment of type 2 diabetes mellitus (T2DM). Through their actions on ATP-sensitive potassium (KATP) channels, sulfonylureas boost insulin release from the pancreatic beta cell mass to restore glucose homeostasis. A limitation of these compounds is the elevated risk of developing hypoglycemia and cardiovascular disease, both potentially fatal complications. Here, we describe the design and development of a photoswitchable sulfonylurea, JB253, which reversibly and repeatedly blocks KATP channel activity following exposure to violet-blue light. Using in situ imaging and hormone assays, we further show that JB253 bestows light sensitivity upon rodent and human pancreatic beta cell function. Thus, JB253 enables the optical control of insulin release and may offer a valuable research tool for the interrogation of KATP channel function in health and T2DM.
Combined biophysical and soluble factor modulation induces cardiomyocyte differentiation from human muscle derived stem cells
Authors: Tchao Jason , Han Lu , Lin Bo , Yang Lei , Tobita Kimimasa 
Published: October 2014

AbstractCellular cardiomyoplasty has emerged as a novel therapy to restore contractile function of injured failing myocardium. Human multipotent muscle derived stem cells (MDSC) can be a potential abundant, autologous cell source for cardiac repair. However, robust conditions for cardiomyocyte (CM) differentiation are not well established for this cell type. We have developed a new method for CM differentiation from human MDSC that combines 3-dimensional artificial muscle tissue (AMT) culture with temporally controlled biophysical cell aggregation and delivery of 4 soluble factors (microRNA-206 inhibitor, IWR-1, Lithium Chloride and BMP-4) (4F-AG-AMT). The 4F-AG-AMT displayed cardiac-like response to β-adrenergic stimulation and contractile properties. 4F-AG-AMT expressed major cardiac (NKX2-5, GATA4, TBX5, MEF2C) transcription factors and structural proteins. They also express cardiac gap-junction protein, connexin-43, similar to CMs and synchronized spontaneous calcium transients. These results highlight the importance of temporal control of biophysical and soluble factors for CM differentiation from MDSCs.
Serpin latency transition at atomic resolution
Authors: Cazzolli Giorgia , Wang Fang , a Beccara Silvio , Gershenson Anne , Faccioli Pietro , Wintrode Patrick L. 
Published: October 2014

SignificanceInhibitory serpin plasminogen activator inhibitor 1 (PAI-1) helps regulate blood clot clearance, and high levels of active PAI-1 are associated with poor cancer prognoses and cardiovascular diseases. PAI-1 transitions from an active form to an inactive, latent form via large structural rearrangements. Our simulations provide the first realistic atomistic characterization, to our knowledge, of this transition. They correctly predict the kinetic effects of mutations and explain why PAI-1 binding to specific molecules accelerates the transition. Structures from these simulations provide templates to design drugs that speed up the latency transition, with potentially important biomedical applications. Serpins are large proteins, and the first-passage times of the simulated conformational transitions are many orders of magnitude longer than the time intervals accessible using conventional molecular dynamics.
Redox chemistry in the phosphorus biogeochemical cycle
Authors: Pasek Matthew A. , Sampson Jacqueline M. , Atlas Zachary 
Published: October 2014

Significance
Phosphorus is an important nutrient for living organisms. Phosphorus is generally considered to bear a 5+ oxidation state, but several lower redox states have been reported, including the toxic gas phosphine. We show here that the lower redox states of phosphorus are common in Florida water samples, and that based on the global concentration of phosphine, we might expect to see 5−15% of all dissolved phosphorus in a lower redox state.
eIF4AIII enhances translation of nuclear cap-binding complex–bound mRNAs by promoting disruption of secondary structures in 5′UTR
Authors: Choe Junho , Ryu Incheol , Park Ok Hyun , Park Joori , Cho Hana , Yoo Jin Seon , Chi Sung Wook , Kim Min Kyung , Song Hyun Kyu , Kim Yoon Ki 
Published: October 2014

Significance
Two major cap-binding components can drive mammalian translation initiation: the nuclear cap-binding complex (CBC) and eukaryotic translation initiation factor 4E (eIF4E). Although eIF4E-dependent translation has been well characterized, the mechanism of CBC-dependent translation remains unclear. Here, we demonstrate the previously unappreciated role of eIF4AIII in CBC-dependent translation. eIF4AIII is traditionally considered a component of the exon junction complex loaded onto mRNAs after splicing. In addition, we found that eIF4AIII can be recruited to the 5′-end of CBC-associated mRNA and promotes the translation of CBC-associated mRNA by helping to unwind secondary structures in 5′UTR. Therefore, our data provide evidence that eIF4AIII is a translation initiation factor specifically required for translation of CBC-associated mRNAs.
Sea level and global ice volumes from the Last Glacial Maximum to the Holocene
Authors: Lambeck Kurt , Rouby Hélène , Purcell Anthony , Sun Yiying , Sambridge Malcolm 
Published: October 2014

SignificanceSeveral areas of earth science require knowledge of the fluctuations in sea level and ice volume through glacial cycles. These include understanding past ice sheets and providing boundary conditions for paleoclimate models, calibrating marine-sediment isotopic records, and providing the background signal for evaluating anthropogenic contributions to sea level. From ∼1,000 observations of sea level, allowing for isostatic and tectonic contributions, we have quantified the rise and fall in global ocean and ice volumes for the past 35,000 years. Of particular note is that during the ∼6,000 y up to the start of the recent rise ∼100−150 y ago, there is no evidence for global oscillations in sea level on time scales exceeding ∼200 y duration or 15−20 cm amplitude.
Transfer of noncoding DNA drives regulatory rewiring in bacteria
Authors: Oren Yaara , Smith Mark B. , Johns Nathan I. , Kaplan Zeevi Millie , Biran Dvora , Ron Eliora Z. , Corander Jukka , Wang Harris H. , Alm Eric J. , Pupko Tal 
Published: October 2014

Significance
The rapid pace of evolution in bacteria is widely attributed to the promiscuous horizontal transfer and recombination of protein-coding genes. However, it has not been investigated if the same forces also drive the evolution of noncoding regulatory regions. Here, we establish that regulatory regions can “switch” between nonhomologous alternatives and that switching is ubiquitous, occurring across the bacterial domain. We show that regulatory switching has a strong impact on promoter architecture and expression divergence. Further, we demonstrate that regulatory transfer facilitates rapid phenotypic diversification of a human pathogen. This regulatory mobility enables bacterial genes to access a vast pool of potential regulatory elements, facilitating efficient exploration of the regulatory landscape.
Sulforaphane treatment of autism spectrum disorder (ASD)
Authors: Singh Kanwaljit , Connors Susan L. , Macklin Eric A. , Smith Kirby D. , Fahey Jed W. , Talalay Paul , Zimmerman Andrew W. 
Published: October 2014

Significance
Autism spectrum disorder (ASD), encompassing impaired communication and social interaction, and repetitive stereotypic behavior and language, affects 1–2% of predominantly male individuals and is an enormous medical and economic problem for which there is no documented, mechanism-based treatment. In a placebo-controlled, randomized, double-blind clinical trial, daily oral administration for 18 wk of the phytochemical sulforaphane (derived from broccoli sprouts) to 29 young men with ASD substantially (and reversibly) improved behavior compared with 15 placebo recipients. Behavior was quantified by both parents/caregivers and physicians by three widely accepted measures. Sulforaphane, which showed negligible toxicity, was selected because it upregulates genes that protect aerobic cells against oxidative stress, inflammation, and DNA-damage, all of which are prominent and possibly mechanistic characteristics of ASD.
CMG helicase and DNA polymerase ε form a functional 15-subunit holoenzyme for eukaryotic leading-strand DNA replication
Authors: Langston Lance D. , Zhang Dan , Yurieva Olga , Georgescu Roxana E. , Finkelstein Jeff , Yao Nina Y. , Indiani Chiara , O’Donnell Mike E. 
Published: October 2014

Significance
All cells must replicate their chromosomes prior to cell division. This process is carried out by a collection of proteins, known as the replisome, that act together to unwind the double helix and synthesize two new DNA strands complementary to the two parental strands. The details of replisome function have been worked out for bacteria but are much less well understood for eukaryotic cells. We have developed a system for studying eukaryotic replisome function in vitro using purified proteins. Using this system, we have identified a direct interaction between the component that unwinds the DNA, the CMG (Cdc45-MCM-GINS) helicase, and the component that replicates the leading strand, DNA polymerase ε, to form a large helicase–polymerase holoenzyme comprising 15 separate proteins.
Modeling the Dynamics of Oral Poliovirus Vaccine Cessation
Authors: Thompson Kimberly M. , Duintjer Tebbens Radboud J. 
Published: October 2014

Abstract
Background.  Oral poliovirus vaccine (OPV) results in an ongoing burden of poliomyelitis due to vaccine-associated paralytic poliomyelitis and circulating vaccine-derived polioviruses (cVDPVs). This motivates globally coordinated OPV cessation after wild poliovirus eradication.
Methods.  We modeled poliovirus transmission and OPV evolution to characterize the interaction between population immunity, OPV-related virus prevalence, and the emergence of cVDPVs after OPV cessation. We explored strategies to prevent and manage cVDPVs for countries that currently use OPV for immunization and characterized cVDPV emergence risks and OPV use for outbreak response.
Results.  Continued intense supplemental immunization activities until OPV cessation represent the best strategy to prevent cVDPV emergence after OPV cessation in areas with insufficient routine immunization coverage. Policy makers must actively manage population immunity before OPV cessation to prevent cVDPVs and aggressively respond if prevention fails. Sufficiently aggressive response with OPV to interrupt transmission of the cVDPV outbreak virus will lead to die-out of OPV-related viruses used for response in the outbreak population. Further analyses should consider the risk of exportation to other populations of the outbreak virus and any OPV used for outbreak response.
Conclusions.  OPV cessation can successfully eliminate all circulating live polioviruses in a population. The polio end game requires active risk management.
Modeling the spectral energy distribution of 3C 454.3 in a “flat” broad-line region scenario
Authors: Lei Maichang , Wang Jiancheng 
Published: October 2014

Abstract
The broad-line region (BLR) of flat-spectrum radio quasars (FSRQs) could have a “flat” geometrical structure to allow GeV gamma-ray photons to escape, to produce the observed gamma-ray flares with short timescales. In this paper, we collect the quasi-simultaneous spectral energy distributions (SEDs) of the FSRQ 3C 454.3 obtained by the multi-wavelength campaigns spanning from 2007 July to 2011 January, and use a model with a “flat” structure BLR, an accretion disc and a dust torus to explain the SEDs of gamma-ray outbursts. We obtain the following results: (i) the jet is almost in equipartition between magnetic and particle energy densities during the outbursts; (ii) when the emitting region is located inside the cavity of the BLR, the covering factor fBLR of the BLR is very small—as the emitting region goes into the BLR structure, fBLR increases; (iii) the aperture angle α describing the BLR structure is about 45°; (iv) the central black hole mass is about 5 × 108 M⊙ rather than 4.4 × 109 M⊙.
Influences of Breast Milk Composition on Gastric Emptying in Preterm Infants
Authors: Perrella Sharon L. , Hepworth Anna R. , Simmer Karen N. , Geddes Donna T. 
Published: October 2014

ABSTRACTObjectives:The aim of the present study was to determine whether specific biochemical and energy concentrations influence gastric emptying of unfortified and fortified mother's own milk (MOM) in stable preterm infants, and whether gastric emptying differs between feeds of unfortified MOM and feeds fortified with S‐26 or FM 85 human milk fortifier (HMF) when infants are fed the same volume under similar conditions. Influences of infant gestation, age, and weight, and feed characteristics were also explored.Methods:Stomach volumes of 25 paired unfortified and fortified MOM feeds were monitored prefeed and postfeed delivery and at 30‐minute intervals thereafter. For each feed, MOM samples were analyzed to determine concentrations of total protein, casein, whey, carbohydrate, lactose, fat, and energy. Fortified feed compositions were calculated by adding fortifier biochemical and energy concentrations to unfortified MOM concentrations. Ultrasound images were used to calculate infant stomach volumes. Statistical comparisons were made of paired stomach volume measurements.Results:Higher feed concentrations of casein were associated with faster gastric emptying during feed delivery (P = 0.007). When compared with unfortified MOM, S‐26 fortified feeds emptied similarly, whereas FM 85 fortified feeds emptied more slowly both during feed delivery and during the postprandial period (P = 0.002, <0.001, respectively). Gastric emptying was slower for 2‐hourly feeds compared with that for 3‐hourly feeds (P = 0.003) and in supine position compared with that in prone (P = 0.001).Conclusions:Breast milk composition influences gastric emptying in stable preterm infants, with feeds of higher casein concentration emptying faster during feeding than otherwise equivalent feeds, and FM 85 fortified MOM emptying more slowly than unfortified MOM.
Evaluation of factors and approaches affecting emergency department space planning
Authors: Pascale Federica , Achour Nabil , D.F. Price Andrew , Polverino Francesco 
Published: October 2014

Purpose
– This paper aims to evaluate emergency department (ED) design space planning approaches and draw lessons for developing more resilient and integrated ED guidelines. Two key objectives have been set; these include: exploring potential factors affecting the ED performance, and investigate how ED space planning is addressed internationally through the evaluation of international case studies and design guidelines.

Design/methodology/approach
– A robust research method has been adopted including comprehensive literature review in addition to 76 case studies from Italy and the USA.

Findings
– Findings show that the important factors in defining ED space requirements are attendance variability, vulnerable groups and mass casualty events. The study concludes that current design guidelines and approaches need to be updated to meet with the current and future demand by taking into account design performance: effectiveness, efficiency and resilience, to avoid underestimating ED space; and that the US EDs are in a better position, than Italian EDs, to increase capacity when needed.

Originality/value
– The contribution of this study is in providing a tangible “understanding” of factors influencing ED design and prepares a firm ground to develop more resilient and integrated design guidelines, able to meet current, exceptional and long-term needs of EDs. The study also shows that research can provide a valuable contribution to improve ED design which needs to feed more in practice to improve design process and guidelines.