bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Modelling of Macrosegregation during Twin-Roll Casting
Authors: Rodrigues C M G , Ludwig A , Kharicha A , Wu M , Vakhrushev A 
Published: May 2019

Abstract
Solidification during twin-roll casting happens by cooling of the melt between two counter-rotating rolls, where the molten alloy is constantly fed in. For an inoculated Al-melt, grain growth leads to a gradual increase of solid fraction, so that a coherent solid network forms. Depending on the process condition, this solid network might be subjected to compression within the gap between the two rolls. By using a two-phase volume average model that accounts for (i) transport and growth of spherical grains within a flowing melt, (ii) formation of a coherent solid network above a specific solid fraction and (iii) viscoplastic flow of the solid network saturated with interstitial melt during casting and compression, the process is numerically analysed. It is found that an optimum process with minimum macrosegregation can be achieved for conditions where the kissing point of the two viscoplastic semi-solid shells nearly coincides with the roll nip. It is demonstrated how casting speed, cooling intensity and strand thickness must be related to hit the optimum process window.
Simulation of casting filling process using the lattice Boltzmann method
Authors: Zhang Y J , Qian X W , Zhou J X , Yin Y J , Shen X , Ji X Y , Huang J L 
Published: May 2019

Abstract
Numerical simulation of casting filling process with complex shape is time-consuming. Compared with the traditional SOLA-VOF method, the lattice Boltzmann method (LBM) calculates the pressure field by particle distribution functions instead of the correction of the velocity and pressure fields, which greatly simplifies the calculation process. In addition, the LBM provides a flexible approach which can be easily parallelized. In this study, the LBM is employed to simulate casting filling process. An implementation of a volume-of-fluid (VOF) method within the lattice Boltzmann framework is proposed to capture the free surface of the casting filling process. A Smagorinsky large eddy simulation (LES) model is adopted to improve the numerical stability of the LBM. An adaptive time stepping technique is implemented to ensure an efficient and stable simulation. The model is validated by the experimental and simulation results of Campbell box filling process. The filling process of complex casting is simulated, and the result is compared with the filling process obtained by the SOLA-VOF method. The prediction accuracy and reliability of free surface profile is analysed.
Continuous Casting of High Carbon Steel: How Does Hard Cooling Influence Solidification, Micro - and Macro Segregation?
Authors: Nicholas Grundy A. , Münch Steve , Feldhaus Stephan , Bratberg Johan 
Published: May 2019

Abstract
One technology that is often employed in continuous casting of high-carbon steel billets to minimize centre - (or macro) segregation is hard secondary cooling. Investigations unanimously show, that hard cooling significantly reduces macro-segregation, but a mechanism for the reduced segregation is rarely given. In this paper the solidification of high carbon tire cord grade C80D cast as a 150x150 mm billet is calculated using the proprietary SMS Group solidification simulation package CHILL using steel properties calculated with the Thermo-Calc Software package and TCFE steels database. The obtained cooling rates in the billet for hard and soft secondary cooling are used to run solidification simulations considering solute redistribution using the diffusion module DICTRA. It is shown that for cooling rates achieved in continuous casting the steel solidifies far away from equilibrium. The solidification profile and solidus temperature lie in between the Scheil solidification model and the para-equilibrium Scheil model with carbon defined as a fast diffusing element. The calculated cooling rates and temperature gradients are used to simulate the solidification microstructure 20 mm from the billet surface using the phase field approach and the MICRESS® software package linked to Thermo-Calc through the TQ interface. This model clearly shows, that the most probable mechanism by which hard cooling reduces segregation is trapping of solutes between the intricately branched dendrite microstructure that results from the steep temperature gradients achieved when applying hard secondary cooling.
Three-dimensional study of nodule clustering and heterogeneous strain localization for tailored material properties in ductile iron
Authors: Olofsson Jakob , Salomonsson Kent , Dahle Arne K. , Mathiesen Ragnvald H. 
Published: May 2019

Abstract
Tailored heterogeneous distributions of microstructural features enable extraordinary material performance in biological and physiological structures such as trees, the aortic arch, human teeth and dinosaur skulls. In ductile iron, a heterogeneous distribution in size and morphology of graphite nodules and variations of the fractions of ferrite and pearlite are created during solidification, and varies as a function of parameters such as local cooling rate, segregation and flow. In the current work, the size distribution as well as the orientation and relation between graphite nodules is obtained by a three-dimensional reconstruction of a ductile iron microstructure from X-ray tomography. The effect of the nodule morphology and clustering on the localization of plastic strains is studied numerically using finite element analysis of the reconstructed microstructure. Real castings have a variation in geometry, solidification conditions and are subjected to variations in loads. A framework for optimized geometry and solidification conditions in order to design and deliver castings with tailored local material performance is proposed.
A nonlocal transport equation describing roots of polynomials under differentiation
Authors: Steinerberger Stefan 
Published: May 2019

Let

p
n

p_n

be a polynomial of degree

n
n

having all its roots on the real line distributed according to a smooth function

u
(
0
,
x
)

u(0,x)

. One could wonder how the distribution of roots behaves under iterated differentation of the function, i.e., how the density of roots of

p
n

(
k
)

p_n^{(k)}

evolves. We derive a nonlinear transport equation with nonlocal flux

u
t

+

1
π

(
arctan
⁡

(

H
u

u

)

)

x

=
0

on

supp
⁡

{
u
>
0
}

,

\begin{equation*} u_t + \frac {1}{\pi }\left ( \arctan { \left ( \frac {Hu}{ u}\right )} \right )_x = 0 \qquad \text {on} ~\operatorname {supp} \left \{u>0\right \}, \end{equation*}

where

H
H

is the Hilbert transform. This equation has three very different compactly supported solutions: (1) the arcsine distribution

u
(
t
,
x
)
=
(
1
−

x
2

)

−
1

/

2

χ

(
−
1
,
1
)

u(t,x) = (1-x^2)^{-1/2} \chi _{(-1,1)}

, (2) the family of semicircle distributions

u
(
t
,
x
)
=

2
π

(
T
−
t
)
−

x
2

,

\begin{equation*} u(t,x) = \frac {2}{\pi } \sqrt {(T-t) - x^2}, \end{equation*}

and (3) a family of solutions contained in the Marchenko–Pastur law.
The Effects of Preventive Home Visits on Older People’s Use of Health Care and Social Services and Related Costs
Authors: Liimatta Heini A , Lampela Pekka , Kautiainen Hannu , Laitinen-Parkkonen Pirjo , Pitkala Kaisu H 
Published: May 2019

Abstract

Background
We use data from a randomized controlled trial on preventive home visits exploring effectiveness on health-related quality of life. In this article, we examine the intervention’s cost-effectiveness and effects on quality-adjusted life years in older home-dwelling adults.

Methods
There were 422 independently home-dwelling participants in the randomized, controlled trial, all aged more than 75 years, with equal numbers in the control and intervention groups. The intervention took place in a municipality in Finland and consisted of multiprofessional preventive home visits. We gathered the data on health care and social services use from central registers and medical records during 1 year before the intervention and 2 years after the intervention. We analyzed the total health care and social services use and costs per person-years and the difference in change in health-related quality of life as measured using the 15D measure. We calculated quality-adjusted life years and incremental cost-effectiveness ratios.

Results
There was no significant difference in baseline use of services or in the total use and costs of health care and social services during the 2-year follow-up between the two groups. In the intervention group, health-related quality of life declined significantly more slowly compared with the control group (–0.015), but there was no significant difference in quality-adjusted life years gained between the groups. The cost-effectiveness plane showed 60% of incremental cost-effectiveness ratios lying in the dominant quadrant, representing additional effects with lower costs.

Conclusions
This multiprofessional preventive home visit intervention appears to have positive effects on health-related quality of life without accruing additional costs.

The clinical trial registration number
ACTRN12616001411437.
Horizontal Reputation and Strategic Audience Management
Authors: Bouvard Matthieu , Lévy Raphaël 
Published: May 2019

Abstract
We study how a decision maker uses his reputation to simultaneously influence the actions of multiple receivers with heterogenous biases. The reputational payoff is single-peaked around a bliss reputation at which the incentives of the average receiver are perfectly aligned. We establish the existence of two equilibria characterized by repositioning toward this bliss reputation that only differ through a multiplier capturing the efficiency of reputational incentives. Repositioning is moderate in the more efficient equilibrium, but the less efficient equilibrium features overreactions, and welfare may then be lower than in the no-reputation case. We highlight how strategic audience management (e.g., centralization, delegation to third parties with dissenting objectives) alleviates inefficient reputational incentives, and how multiple organizational or institutional structures may arise in equilibrium as a result.
3D Exoscope System in Neurosurgery—Comparison of a Standard Operating Microscope With a New 3D Exoscope in the Cadaver Lab
Authors: Herlan Stephan , Marquardt Jakob S , Hirt Bernhard , Tatagiba Marcos , Ebner Florian H 
Published: May 2019

Abstract

BACKGROUND
For decades, the operating microscope has been the “gold standard” visualization device in neurosurgery. The development of endoscopy revolutionized different surgical disciplines, whereas in neurosurgery, the endoscope is commonly used as an additional device more than as single visualization tool. Invention of a 3D exoscope system opens new possibilities in visualization and ergonomics in neurosurgery.

OBJECTIVE
To assess the prototype of a 3D exoscope (3D exoscope, year of manufacture 2015, FA Aesculap, Tüttlingen, Germany) as neurosurgical visualization device in comparison to a standard operating microscope.

METHODS
A pterional approach was performed in 3 ETOH-fixed specimens (6 sides). A standard operating microscope was compared to a 3D exoscope prototype. Dimensions like visual field, magnification, illumination, ergonomics, depth effect, and 3D impression were compared.

RESULTS
In all approaches, the structures of interest could be clearly visualized with both devices. Magnification showed similar results. The exoscope had more magnification potential, whereas the visual quality got worse in higher magnification levels. The illumination showed better results in the microscope. Surgeons felt more comfortable with the 3D exoscope, concerning ergonomic considerations. Depth effect and 3D impression showed similar results. None of the surgeons felt uncomfortable using the exoscope.

CONCLUSION
The operating microscope is the gold standard visualization tool in neurosurgery because of its illumination, stereoscopy, and magnification. Nevertheless, it causes ergonomic problems. The prototype of a 3D exoscope showed comparable features in visual field, stereoscopic impression, and magnification, with a clear benefit concerning the ergonomic possibilities.
Endoscopic Interhemispheric Disconnection for Intractable Multifocal Epilepsy: Surgical Technique and Functional Neuroanatomy
Authors: Sufianov Albert A , Cossu Giulia , Iakimov Iurii A , Sufianov Rinat A , Markin Egor S , Stefanov Stefan Z , Zemmoura Ilyess , Messerer Mahmoud , Daniel Roy T 
Published: May 2019

Abstract

BACKGROUND
Callosotomy represents a palliative procedure for intractable multifocal epilepsy. The extent of callosotomy and the benefits of adding anterior and posterior commissurotomy are debated.

OBJECTIVE
To describe a new technique of a purely endoscopic procedure to disconnect the corpus callosum, the anterior, posterior, and habenular commissures through the use of a single burr hole via a transfrontal transventricular route.

METHODS
Our surgical series was retrospectively reviewed in terms of seizure control (Engel's class) and complication rate. Five cadaveric specimens were used to demonstrate the surgical anatomy of commissural fibers and third ventricle.

RESULTS
The procedure may be divided into 3 steps: (1) endoscopic transventricular transforaminal anterior commissure disconnection; (2) disconnection of posterior and habenular commissures; and (3) total callosotomy. Fifty-seven patients were included in the analysis. A favorable outcome in terms of epilepsy control (Engel class 1 to 3) was found in 71.4% of patients undergoing callosotomy coupled with anterior, posterior, and habenular commissure disconnection against 53% of patients with isolated callosotomy (P = .26). Patients with drop attacks had better epilepsy outcome independently from the surgical procedure used.

CONCLUSION
The full endoscopic callosotomy coupled with disconnection of anterior, posterior and habenular commissures is a safe alternative to treat multifocal refractory epilepsy. A gain in seizure outcome might be present in this cohort of patients treated with total interhemispheric disconnection when compared with isolated callosotomy. Larger studies are required to confirm these findings.
New Warning for Fluoroquinolone Antibiotics
Authors: Aschenbrenner Diane S. 
Published: May 2019

The Food and Drug Administration has added a warning to the labeling of all fluoroquinolone antibiotics stating that these drugs can increase the risk of rupture or dissection of aortic aneurysms.NPs should avoid prescribing fluoroquinolones to patients at risk for aortic aneurysms unless no other therapy is available.
Hormonal regulation of Semaphorin 7a in ER+ breast cancer drives therapeutic resistance
Authors: Crump Lyndsey S , Wyatt Garhett , Rutherford Taylor R , Richer Jennifer K , Porter Weston W , Lyons Traci R 
Published: May 2019

ABSTRACTApproximately 70% of all breast cancers are estrogen receptor positive (ER+BC) and endocrine therapy has improved survival for patients with ER+BC. Yet, up to half of these tumors recur within 20 years. Recurrent ER+BCs develop resistance to endocrine therapy; thus, novel targets are needed to treat recurrent ER+BC. We found that semaphorin 7A (SEMA7A) confers significantly decreased patient survival rates in ER+BC. We show that SEMA7A is hormonally regulated in ER+BC, but its expression does not uniformly decrease with anti-estrogen treatments. Additionally, overexpression of SEMA7A in ER+ cell lines drives increased in vitro growth in the presence of estrogen-deprivation, tamoxifen, and fulvestrant. In in vivo studies, we found that SEMA7A confers primary tumor resistance to fulvestrant and, importantly, induced lung metastases. Finally, we identify pro-survival signaling as a therapeutic vulnerability of ER+SEMA7A+ tumors and propose that targeting with inhibitors of survival signaling such as venetoclax may have efficacy for treating SEMA7A+ tumors.SIGNIFICANCEWe report that SEMA7A predicts for, and likely contributes to, poor response to standard-of-care therapies and suggest that patients with SEMA7A+ER+ tumors may benefit from alternative therapeutic strategies.
Exploring Conformational Transitions and Free Energy Profiles of Proton Coupled Oligopeptide Transporters
Authors: Batista Mariana R. B. , Watts Anthony , Costa-Filho Antonio J. 
Published: May 2019

AbstractProteins involved in peptide uptake and transport belong to the proton-coupled oligopeptide transporter (POT) family. Crystal structures of POT family members reveal a common fold consisting of two domains of six transmembrane α helices that come together to form a “V” shaped transporter with a central substrate binding site. Proton coupled oligopeptide transporters operate through an alternate access mechanism, where the membrane transporter undergoes global conformational changes, alternating between inward-facing (IF), outward-facing (OF) and occluded (OC) states. Conformational transitions are promoted by proton and ligand binding, however, due to the absence of crystallographic models of the outward-open state, the role of H+ and ligands are still not fully understood. To provide a comprehensive picture of the POT conformational equilibrium, conventional and enhanced sampling molecular dynamics simulations of PepTst in the presence or absence of ligand and protonation were performed. Free energy profiles of the conformational variability of PepTst were obtained from microseconds of adaptive biasing force (ABF) simulations. Our results reveal that both, proton and ligand, significantly change the conformational free energy landscape. In the absence of ligand and protonation, only transitions involving IF and OC states are allowed. After protonation of the residue Glu300, the wider free energy well for Glu300 protonated PepTst indicates a greater conformational variability relative to the apo system, and OF conformations becames accessible. For the Glu300 Holo-PepTst, the presence of a second free energy minimum suggests that OF conformations are not only accessible, but also, stable. The differences in the free energy profiles demonstrate that transitions toward outward facing conformation occur only after protonation and, probably, this should be the first step in the mechanism of peptide transport. Our extensive ABF simulations provide a fully atomic description of all states of the transport process, offering a model for the alternating access mechanism and how protonation and ligand control the conformational changes.Graphical TOC Entry
Mlh1 haploinsufficiency induces microsatellite instability specifically in intestine
Authors: Shrestha Kul S. , Aska Elli-Mari , Tuominen Minna M. , Kauppi Liisa 
Published: May 2019

AbstractTumors of Lynch syndrome (LS) patients display high levels of microsatellite instability (MSI), which results from complete loss of DNA mismatch repair (MMR), in line with Knudson’s two-hit hypothesis. Why some organs, in particular those of the gastrointestinal (GI) tract, are especially prone to tumorigenesis in LS remains unknown. We hypothesized that MMR is haploinsufficient in certain tissues, compromising microsatellite stability in a tissue-specific manner before tumorigenesis. Using mouse genetics, we tested how levels of MLH1, a central MMR protein, affect microsatellite stability in vivo and whether elevated MSI is detectable prior to loss of MMR function and to neoplastic growth. We assayed MSI by sensitive single-molecule PCR in normal jejunum and spleen of 4- and 12-month old Mlh1+/+, Mlh1+/− and Mlh1−/− mice, accompanied by measurements of Mlh1 mRNA and MLH1 protein expression levels.While spleen MLH1 levels of Mlh1+/− mice were, as expected, approximately 50% compared to wildtype mice, MLH1 levels in jejunum varied substantially between individual Mlh1+/− mice and decreased with age. Apparently, Mlh1+/− mice with soma-wide Mlh1 promoter methylation were the most venerable to MLH1 expression level decrease in jejunum. MLH1 levels (prior to complete loss of the protein) inversely correlated with MSI severity in Mlh1+/− jejunum, while in spleens of the same mice, MLH1 levels and microsatellites remained stable. Thus, Mlh1 haploinsufficiency affects specifically the intestine where MMR levels are particularly labile, inducing MSI in normal cells long before neoplasia. A similar mechanism likely also operates in the human GI epithelium, and could explain the wide range in age of onset of LS-associated tumorigenesis.
Tyr1 phosphorylation promotes the phosphorylation of Ser2 on the C-terminal domain of RNA polymerase II by P-TEFb
Authors: Mayfield Joshua E. , Irani Seema , Escobar Edwin E. , Zhang Zhao , Burkholder Nathanial T. , Robinson Michelle R. , Mehaffey M. Rachel , Sipe Sarah N. , Yang Wanjie , Prescott Nicholas A. , Kathuria Karan R. , Liu Zhijie , Brodbelt Jennifer S. , Zhang Yan 
Published: May 2019

SummaryThe Positive Transcription Elongation Factor b (P-TEFb) phosphorylates Ser2 residues of RNA polymerase II’s C-terminal domain (CTD) and is essential for the transition from transcription initiation to elongationin vivo. Surprisingly, P-TEFb exhibits Ser5 phosphorylation activityin vitro. The mechanism garnering Ser2 specificity to P-TEFb remains elusive and hinders understanding of the transition from transcription initiation to elongation. Throughin vitroreconstruction of CTD phosphorylation, mass spectrometry analysis, and chromatin immunoprecipitation sequencing (ChIP-seq) analysis we uncover a mechanism by which Tyr1 phosphorylation directs the kinase activity of P-TEFb and alters its specificity from Ser5 to Ser2. The loss of Tyr1 phosphorylation causes a reduction of phosphorylated Ser2 and accumulation of RNA polymerase II in the promoter region as detected by ChIP-seq. We demonstrate the ability of Tyr1 phosphorylation to generate a heterogeneous CTD modification landscape that expands the CTD’s coding potential. These findings provide direct experimental evidence for a combinatorial CTD phosphorylation code wherein previously installed modifications direct the identity and abundance of subsequent coding events by influencing the behavior of downstream enzymes.
Sensory Stimulation-Induced Astrocytic Calcium Signaling in Electrically Silent Ischemic Penumbra
Authors: Murmu Reena P. , Fordsmann Jonas C. , Cai Changsi , Brazhe Alexey , Thomsen Kirsten J. , Lauritzen Martin 
Published: May 2019

AbstractMiddle cerebral artery occlusion (MCAO) induces ischemia characterized by a densely ischemic focus, and a less densely ischemic penumbral zone in which neurons and astrocytes display age-dependent dynamic variations in spontaneous Ca2+ activities. However, it is unknown whether penumbral nerve cells respond to sensory stimulation early after stroke onset, which is critical for understanding stimulation-induced stroke therapy. In this study, we investigated the ischemic penumbra’s capacity to respond to somatosensory input. We examined adult (3- to 4-month-old) and old (18- to 24-month-old) male mice at 2–4 hours after MCAO, using two-photon microscopy to record somatosensory stimulation-induced neuronal and astrocytic Ca2+ signals in the ischemic penumbra. In both adult and old mice, MCAO abolished spontaneous and stimulation-induced electrical activity in the penumbra, and strongly reduced stimulation-induced Ca2+ responses in neuronal somas (35–82%) and neuropil (92–100%) in the penumbra. In comparison, after stroke, stimulation-induced astrocytic Ca2+ responses in the penumbra were only moderately reduced (by 54–62%) in adult mice, and were even better preserved (reduced by 31–38%) in old mice.Our results suggest that somatosensory stimulation evokes astrocytic Ca2+ activity in the ischemic penumbra. We hypothesize that the relatively preserved excitability of astrocytes, most prominent in aged mice, may modulate protection from ischemic infarcts during early somatosensory activation of an ischemic cortical area. Future neuroprotective efforts in stroke may target spontaneous or stimulation-induced activity of astrocytes in the ischemic penumbra.