bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat Transfer in Flat-Plate Boundary Layers: A Correlation for Laminar, Transitional, and Turbulent Flow
Authors: Lienhard John H. 
Published: March 2020

Abstract
The laminar and turbulent regimes of a boundary layer on a flat plate are often represented with separate correlations under the assumption of a distinct “transition Reynolds number.” Average heat coefficients are then calculated by integrating across the “transition point.” Experimental data do not show an abrupt transition, but rather an extended transition region in which turbulence develops. The transition region may be as long as the laminar region. Although this transitional behavior has been known for many decades, few correlations have incorporated it. One attempt was made by Stuart Churchill in 1976. Churchill, however, based his curve fit on some doubtful assumptions about the data sets. In this paper, we develop different approximations through a detailed consideration of multiple data sets for 0.7 ⩽ Pr ⩽ 257, 4000 ⩽ Rex ⩽ 4,300,000, and varying levels of freestream turbulence for smooth, sharp-edged plates at zero pressure gradient. The result we obtain is in good agreement with the available measurements and applies smoothly over the full range of Reynolds number for either a uniform wall temperature or a uniform heat flux boundary condition. Fully turbulent air data are correlated to ±11%. Like Churchill's result, this correlation should be matched to the estimated transition condition of any particular flow. We also review the laminar analytical solutions for a uniform wall heat flux, and point out limitations of the classical Colburn analogy.
Genetic Analysis of Mutacin B-Ny266, a Lantibiotic Active against Caries Pathogens
Authors: Dufour Delphine , Barbour Abdelahhad , Chan Yuki , Cheng Marcus , Rahman Taimoor , Thorburn Matthew , Stewart Cameron , Finer Yoav , Gong Siew-Ging , Lévesque Céline M. 
Published: March 2020

ABSTRACT
Bacteriocins are ribosomally synthesized proteinaceous antibacterial peptides. They selectively interfere with the growth of other bacteria. The production and secretion of bacteriocins confer a distinct ecological advantage to the producer in competing against other bacteria that are present in the same ecological niche. Streptococcus mutans, a significant contributor to the development of dental caries, is one of the most prolific producers of bacteriocins, known as mutacins in S. mutans. In this study, we characterized the locus encoding mutacin B-Ny266, a lantibiotic with a broad spectrum of activity. The chromosomal locus is composed of six predicted operon structures encoding proteins involved in regulation, antimicrobial activity, biosynthesis, modification, transport, and immunity. Mutacin B-Ny266 was purified from semisolid cultures, and two inhibitory peptides, LanA and LanA′, were detected. Both peptides were highly modified. Such modifications include dehydration of serine and threonine and the formation of a C-terminal aminovinyl-cysteine (AviCys) ring. While LanA peptide alone is absolutely required for antimicrobial activity, the presence of LanA′ enhanced the activity of LanA, suggesting that B-Ny266 may function as a two-peptide lantibiotic. The activation of lanAA′ expression is most likely controlled by the conserved two-component system NsrRS, which is activated by LanA peptide but not by LanA′. The chromosomal locus encoding mutacin B-Ny266 was not universally conserved in all sequenced S. mutans genomes. Intriguingly, the genes encoding LanAA′ peptides were restricted to the most invasive serotypes of S. mutans.
IMPORTANCE Although dental caries is largely preventable, it remains the most common and costly infectious disease worldwide. Caries is initiated by the presence of dental plaque biofilm that contains Streptococcus mutans, a species extensively characterized by its role in caries development and formation. S. mutans deploys an arsenal of strategies to establish itself within the oral cavity. One of them is the production of bacteriocins that confer a competitive advantage by targeting and killing closely related competitors. In this work, we found that mutacin B-Ny266 is a potent lantibiotic that is effective at killing a wide array of oral streptococci, including nearly all S. mutans strains tested. Lantibiotics produced by oral bacteria could represent a promising strategy to target caries pathogens embedded in dental plaque biofilm.
LAG3(LAG-3,CD223) DNA methylation correlates with LAG3 expression by tumor and immune cells, immune cell infiltration, and overall survival in clear cell renal cell carcinoma
Authors: Klümper Niklas , Ralser Damian J , Bawden Emma Grace , Landsberg Jenny , Zarbl Romina , Kristiansen Glen , Toma Marieta , Ritter Manuel , Hölzel Michael , Ellinger Jörg , Dietrich Dimo 
Published: March 2020

BackgroundLymphocyte activating 3 (LAG3, LAG-3, CD223) is a promising target for immune checkpoint inhibition in clear cell renal cell carcinoma (KIRC). The aim of this study was to investigate the epigenetic regulation ofLAG3in KIRC by methylation.MethodsWe correlated quantitativeLAG3methylation levels with transcriptional activity, immune cell infiltration, and overall survival in a cohort of n=533 patients with KIRC and n=160 normal adjacent tissue (NAT) samples obtained from The Cancer Genome Atlas (TCGA). Furthermore, we analyzedLAG3methylation in peripheral blood mononuclear cells (PBMCs) and KIRC cell lines. We validated correlations between LAG3 expression, immune cell infiltrates, survival, and methylation in an independent KIRC cohort (University Hospital Bonn (UHB) cohort, n=118) by means of immunohistochemistry and quantitative methylation-specific PCR.ResultsWe found differential methylation profiles among PBMCs, NAT, KIRC cell lines, and KIRC tumor tissue. Methylation strongly correlated with LAG3 mRNA expression in KIRCs (TCGA cohort) and KIRC cell lines. In the UHB cohort, methylation correlated with LAG3-positive immune cells and tumor-intrinsic LAG3 protein expression. Furthermore,LAG3methylation strongly correlated with signatures of distinct immune cell infiltrates, an interferon-y signature (TCGA cohort), and immunohistochemically quantified CD45+, CD8+, and CD4+immune cell infiltrates (UHB cohort). LAG3 mRNA expression (TCGA cohort), methylation (both cohorts), and tumor cell-intrinsic protein expression (UHB cohort) was significantly associated with overall survival.ConclusionOur data suggest an epigenetic regulation of LAG3 expression in tumor and immune cells via DNA methylation. LAG3 expression and methylation is associated with a subset of KIRCs showing a distinct clinical course and immunogenicity. Our study provides rationale for further testingLAG3DNA methylation as a predictive biomarker for response to LAG3 immune checkpoint inhibitors.
Do we control gastric residuals unnecessarily in premature newborns? AGRA study: avoidance of gastric residual aspiration
Authors: Akar Selahattin , Turgut Mehmet 
Published: March 2020

Aspiration and evaluation of gastric residuals are commonly performed interventions before each feeding in intensive care units, especially in very low birthweight infants. However, there is no sufficient evidence about the necessity of routine gastric residual aspiration. In this study, we aimed to investigate the time to full enteral intake and the incidence of necrotizing enterocolitis (NEC) in preterm infants in the period with gastric residual aspiration performed before each feeding, and those in the period without gastric residual aspiration.MethodsPreterm infants with a gestational week ≤33 were included in the study. The group with gastric residual control before each feeding consisted of 169 infants, and the group without routine gastric residual aspiration included 122 infants.ResultsThe mean gestational week was 30.37±2.58 and 29.31±3.37 in the group with gastric residual control and in the group without routine residual control, respectively (p<0.05). Birth weight, male gender, and mode of delivery were similar between both groups. The time to full enteral intake was shorter in the group without routine residual control (p<0.05). Total durations of parenteral nutrition, ≥grade 2 NEC, weight at discharge and duration of hospitalization were similar between the groups. Duration of invasive mechanical ventilator support was shorter in the group without routine residual control.ConclusionAvoidance of routine gastric residual aspiration in preterm infants shortens the time to full enteral intake without increasing the incidence of NEC.
Accumulation of chemically degraded organic carbon in the soil profile of Chinese fir plantations
Authors: Wu Qicong , Jiang Xianghe , Zhang Congzhi , Lu Qianwen , Li Jinbiao , Whalen Joann K. , Chen Jinlin 
Published: March 2020

Short-rotation forestry relies on frequent harvests of fast-growing trees, which could deplete soil fertility and soil organic carbon (SOC) reserves. Our objective was to measure the accumulation of SOC fractions, namely the dissolved organic carbon, microbial biomass carbon, particulate organic carbon, permanganate-oxidizable carbon, and non-oxidizable organic carbon, in the soil profile of a Chinese fir plantation. Chronosequences of Chinese fir aged 7, 12, and 33 yr were sampled at depths of 0–20 cm, 20–40 cm, and 40–60 cm. The SOC stock (0–60 cm) was unchanged in the first 12 yr, but after 33 yr, there was a 41%–56% increase in the SOC stock, which reached 81.2 Mg ha−1 (P < 0.05). Permanganate-oxidizable carbon increased with time in the 0–20 cm layer but not in deeper soil depths, whereas non-oxidizable organic carbon accumulated preferentially in the 40–60 cm layer of the soil profile. Inputs of chemically complex plant litter in the soil profile may be important to maintain the oxidizable and non-oxidizable organic carbon in Chinese fir plantations.
Evaluación de Modelo Docente Utilizando Fantomas de Bajo Costo para Entrenamiento en Reparación de Episiotomía.
Authors: Poblete José Andrés , Catalan Cynthia , Vargas Paula , Pineda Rodrigo , Barriga Maria Isabel , Farias Marcelo , Zamboni Milena 
Published: March 2020

Introducción: El creciente aumento de los alumnos de pregrado, asociado a la disminución en el número de partos, han reducido la exposición de los alumnos a procedimientos como la episiotomía.
En este proyecto se implementó un modelo docente utilizando fantomas de bajo costo para el entrenamiento en la reparación de episiotomía. Materiales y Métodos: La instrucción fue realizada a 106 internos de sexto año en grupos de 5 a 10 alumnos y 12 residentes de primer año de la especialidad. Se revisaron los aspectos teóricos relacionados a esta técnica quirúrgica. Cada alumno tenía a su disposión dos fantomas de alta densidad. Los materiales de sutura y el instrumental eran similares a los usados en la práctica clínica. Se realizaron 2 evaluaciones a los alumnos: un minitest teórico y una evaluación de la actividad práctica. Resultados: El resultado promedio de la evaluación teórica fue de 6,3 para los internos de 6º año y de 6,7 para los residentes de primer año de Especialidad. En los aspectos formativos de la actividad práctica, siendo la evaluación máxima 4, los alumnos calificaron la actividad con un 3,66 . En términos de satisfacción de los alumnos con la actividad, sobre una evaluación máxima de 5, los alumnos entregaron una calificación de 4,7. Finalmente, el promedio de los alumnos calificó la actividad muy cerca de lo excelente. Discusión: La implementación de fantomas de espuma de alta densidad, facilita el acceso a modelos de reparación quirúrgica más económicos y permite repetir el ejercicio hasta alcanzar los objetivos establecidos.
TP53 Mutations Predict Sensitivity to Adjuvant Gemcitabine in Patients with Pancreatic Ductal Adenocarcinoma: Next-Generation Sequencing Results from the CONKO-001 Trial
Authors: Sinn Marianne , Sinn Bruno V. , Treue Denise , Keilholz Ulrich , Damm Frederik , Schmuck Rosa , Lohneis Philipp , Klauschen Frederick , Striefler Jana K. , Bahra Marcus , Bläker Hendrik , Bischoff Sven , Pelzer Uwe , Oettle Helmut , Riess Hanno , Budczies Jan , Denkert Carsten 
Published: March 2020

Abstract

Purpose:
We performed next-generation sequencing (NGS) in the CONKO-001 phase III trial to identify clinically relevant prognostic and predictive mutations and conducted a functional validation in The Cancer Genome Atlas (TCGA) sequencing data.

Experimental Design:
Patients of the CONKO-001 trial received curatively intended surgery for pancreatic adenocarcinoma (PDAC) followed by adjuvant chemotherapy with gemcitabine (Gem) or observation only (Obs). Tissue samples of 101 patients were evaluated by NGS of 37 genes. Cox proportional hazard models were applied for survival analysis. In addition, functional genomic analyses were performed in an NGS and RNA-sequencing dataset of 146 pancreatic tumors from TCGA.

Results:
The most common mutations in the CONKO cohort were KRAS (75%), TP53 (60%), SMAD4 (10%), CDKNA2 (9%), as well as SWI/SNF (12%) complex alterations. In untreated patients, TP53 mutations were a negative prognostic factor for disease-free survival (DFS; HR mut vs. WT 2.434, P = 0.005). With respect to gemcitabine treatment, TP53 mutations were a positive predictive factor for gemcitabine efficacy [TP53mut: HR for DFS Gem vs. Obs, 0.235 (0.130 – 0.423; P &lt; 0.001); TP53wt: HR for DFS Gem vs. Obs, 0.794 (0.417 – 1.513; P = 0.483)] with a significant test for interaction (P = 0.003). In the TCGA dataset, TP53 mutations were associated with shortened DFS.

Conclusions:
In CONKO-001, the benefit from adjuvant gemcitabine was confined to the TP53mut patient group. This potentially clinical relevant observation needs to be confirmed in independent prospective studies. The sensitivity of TP53mut PDAC to gemcitabine in CONKO-001 provides a lead for further mechanistic investigations.
Convergent Evolution, Evolving Evolvability, and the Origins of Lethal Cancer
Authors: Pienta Kenneth J. , Hammarlund Emma U. , Axelrod Robert , Amend Sarah R. , Brown Joel S. 
Published: March 2020

Abstract
Advances in curative treatment to remove the primary tumor have increased survival of localized cancers for most solid tumor types, yet cancers that have spread are typically incurable and account for &gt;90% of cancer-related deaths. Metastatic disease remains incurable because, somehow, tumors evolve resistance to all known compounds, including therapies. In all of these incurable patients, de novo lethal cancer evolves capacities for both metastasis and resistance. Therefore, cancers in different patients appear to follow the same eco-evolutionary path that independently manifests in affected patients. This convergent outcome, that always includes the ability to metastasize and exhibit resistance, demands an explanation beyond the slow and steady accrual of stochastic mutations. The common denominator may be that cancer starts as a speciation event when a unicellular protist breaks away from its multicellular host and initiates a cancer clade within the patient. As the cancer cells speciate and diversify further, some evolve the capacity to evolve: evolvability. Evolvability becomes a heritable trait that influences the available variation of other phenotypes that can then be acted upon by natural selection. Evolving evolvability may be an adaptation for cancer cells. By generating and maintaining considerable heritable variation, the cancer clade can, with high certainty, serendipitously produce cells resistant to therapy and cells capable of metastasizing. Understanding that cancer cells can swiftly evolve responses to novel and varied stressors create opportunities for adaptive therapy, double-bind therapies, and extinction therapies; all involving strategic decision making that steers and anticipates the convergent coevolutionary responses of the cancers.
Coronavirus Disease 19 Infection Does Not Result in Acute Kidney Injury: An Analysis of 116 Hospitalized Patients from Wuhan, China
Authors: Wang Luwen , Li Xun , Chen Hui , Yan Shaonan , Li Dong , Li Yan , Gong Zuojiong 
Published: March 2020

<b><i>Background:</i></b> Whether the patients with coronavirus disease 19 (COVID-19) infected by severe acute respiratory syndrome (SARS)-CoV-2 would commonly develop acute kidney injury (AKI) is an important issue worthy of clinical attention. This study aimed to explore the effects of SARS-CoV-2 infection on renal function through analyzing the clinical data of 116 hospitalized COVID-19-confirmed patients. <b><i>Methods:</i></b> One hundred sixteen COVID-19-confirmed patients enrolled in this study were hospitalized in the Department of Infectious Diseases, Renmin Hospital of Wuhan University from January 14 to February 13, 2020. The recorded information includes demographic data, medical history, contact history, potential comorbidities, symptoms, signs, laboratory test results, chest computer tomography scans, and treatment measures. SARS-CoV-2 RNA in 53 urine sediments of enrolled patients was detected by real-time reverse transcription-polymerase chain reaction. <b><i>Results:</i></b> Twelve (10.8%) patients showed mild increase of blood urea nitrogen or creatinine (&#x3c;26 μmol/L within 48 h), and 8 (7.2%) patients showed trace or 1+ albuminuria in 111 COVID-19-confirmed patients without chronic kidney disease (CKD). All these patients did not meet the diagnostic criteria of AKI. In addition, 5 patients with CKD who were undergone regular continuous renal replacement therapy (CRRT) before admission were confirmed infection of SARS-CoV-2 and diagnosed as COVID-19. In addition to therapy for COVID-19, CRRT was also applied 3 times weekly during hospitalization for these 5 patients with CKD. In the course of treatment, the renal function indicators showed stable state in all 5 patients with CKD, without exacerbation of CKD, and pulmonary inflammation was gradually absorbed. All 5 patients with CKD were survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without CKD, and 1 patient had a positive for SARS-CoV-2 open reading frame 1ab from 5 cases with CKD. <b><i>Conclusion:</i></b> AKI was uncommon in COVID-19. SARS-CoV-2 infection does not result in AKI, or aggravate CKD in the COVID-19 patients.
A Synthetic Proposal about the Corinthian Resurrection Deniers
Authors: Harriman K.R. 
Published: March 2020

Abstract
Most standard analyses of the identification of the deniers of the resurrection and the nature of their denial in 1 Cor 15:12 evaluate three sets of options: denial of any post-mortem fate, over-realized eschatology, or dualistic anthropology from Greco-Roman philosophy. The author argues that all of these theories are inadequate, and proposes a theory that identifies the Corinthian resurrection deniers as a cross-section of members from upper and lower classes, with varying levels of education, whose denial of the general resurrection emerges from a variety of sources in philosophy and the myths of popular religion.
Vertical Velocity Profiles in Convectively Coupled Equatorial Waves and MJO: New Diagnoses of Vertical Velocity Profiles in the Wavenumber–Frequency Domain
Authors: Inoue Kuniaki , Adames Ángel F. , Yasunaga Kazuaki 
Published: March 2020

AbstractA new diagnostic framework is developed and applied to ERA-Interim to quantitatively assess vertical velocity (omega) profiles in the wavenumber–frequency domain. Two quantities are defined with the first two EOF–PC pairs of omega profiles in the tropical ocean: a top-heaviness ratio and a tilt ratio. The top-heaviness and tilt ratios are defined, respectively, as the cospectrum and quadrature spectrum of PC1 and PC2 divided by the power spectrum of PC1. They represent how top-heavy an omega profile is at the convective maximum, and how much tilt omega profiles contain in the spatiotemporal evolution of a wave. The top-heaviness ratio reveals that omega profiles become more top-heavy as the time scale (spatial scale) becomes longer (larger). The MJO has the most top-heavy profile while the eastward inertio-gravity (EIG) and westward inertio-gravity (WIG) waves have the most bottom-heavy profiles. The tilt ratio reveals that the Kelvin, WIG, EIG, and mixed Rossby–gravity (MRG) waves, categorized as convectively coupled gravity waves, have significant tilt in the omega profiles, while the equatorial Rossby (ER) wave and MJO, categorized as slow-moving moisture modes, have less tilt. The gross moist stability (GMS), cloud–radiation feedback, and effective GMS were also computed for each wave. The MJO with the most top-heavy omega profile exhibits high GMS, but has negative effective GMS due to strong cloud–radiation feedbacks. Similarly, the ER wave also exhibits negative effective GMS with a top-heavy omega profile. These results may indicate that top-heavy omega profiles build up more moist static energy via strong cloud–radiation feedbacks, and as a result, are more preferable for the moisture mode instability.
Large-Eddy Simulation of Conditionally Neutral Boundary Layers: A Mesh Resolution Sensitivity Study
Authors: Berg Jacob , Patton Edward G. , Sullivan Peter P. 
Published: March 2020

AbstractLarge-eddy simulation (LES) is used to model turbulent winds in a nominally neutral atmospheric boundary layer at varying mesh resolutions. The boundary layer is driven by wind shear with zero surface heat flux and is capped by a stable inversion. Because of entrainment the boundary layer is in a weakly stably stratified regime. The simulations use meshes varying from 1282 × 64 to 10242 × 512 grid points in a fixed computational domain of size (2560, 2560, 896) m. The subgrid-scale (SGS) parameterizations used in the LES vary with the mesh spacing. Low-order statistics, spectra, and structure functions are compared on the different meshes and are used to assess grid convergence in the simulations. As expected, grid convergence is primarily achieved in the middle of the boundary layer where there is scale separation between the energy-containing and dissipative eddies. Near the surface second-order statistics do not converge on the meshes studied. The analysis also highlights differences between one-dimensional and two-dimensional velocity spectra; differences are attributed to sampling errors associated with aligning the horizontal coordinates with the vertically veering mean wind direction. Higher-order structure functions reveal non-Gaussian statistics on all scales, but are highly dependent on the mesh resolution. A generalized logarithmic law and a k−1 spectral scaling regime are identified with mesh-dependent parameters in agreement with previously published results.