bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming Potential of Alternatively Spliced Variants of Fibroblast Growth Factor Receptor 2 in Human Mammary Epithelial Cells
Authors: Moffa Allison B. , Tannheimer Stacey L. , Ethier Stephen P. 
Published: May 2022

Abstract
A breast cancer cell line developed in our laboratory (SUM-52PE) has a 12-fold amplification and high-level overexpression of the oncogene fibroblast growth factor receptor 2 (FGFR2). Previously, nine different alternatively spliced FGFR2 variants were isolated from this cell line. Overexpression of two variants that differ only in their carboxyl termini (C1 and C3) has been successfully accomplished in the immortalized human mammary epithelial cell line H16N2. FGFR2 expression led to the activation of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling cascades. Phosphorylation of the adapter protein FGF receptor substrate 2 is much more robust in the cells expressing the C3 variant of FGFR2 compared with the C1 variant. H16N2 cells expressing the full-length FGFR2 with the C1 or C3 carboxyl terminus were tested for their ability to grow under epidermal growth factor (EGF)–independent conditions, in soft agar, and for their ability to invade naturally occurring basement membranes and compared with the parental SUM-52PE cell line. All three cell lines grew under EGF-independent conditions and all were inhibited by the FGFR family specific inhibitor PD173074. The full-length FGFR2-C1 and FGFR2-C3 variants grew robustly in soft agar similar to the parental cell line SUM-52PE. However, cells expressing the C3 variant formed large colonies in agar in both insulin-free and EGF-free medium, whereas the cells expressing the C1 variant required insulin for growth. Soft agar growth was also inhibited by PD173074. Because SUM-52PE was developed from a metastatic breast carcinoma, the FGFR2-overexpressing cell lines were assessed for their ability to invade sea urchin embryo cell membranes. H16N2 cells expressing the C1 carboxyl terminus failed to invade sea urchin embryo cell membranes. By contrast, FGFR2-C3-expressing cells were as invasive as the SUM-52 breast cancer cells and erbB-2-overexpressing H16N2 cells. These results indicate that FGFR2 is a transforming oncogene in human mammary epithelial cells when expressed to levels similar to that found in breast cancer cells with FGFR2 gene amplification. Furthermore, the results suggest that different splice variants have differing transforming activities and that signaling from variants expressing the C3 carboxyl terminus results in more autonomous signaling, cell growth, and invasion.
Inhibition of Hypoxia-Inducible Factor Is Sufficient for Growth Suppression of VHL−/− Tumors
Authors: Zimmer Michael , Doucette Darrell , Siddiqui Naila , Iliopoulos Othon 
Published: May 2022

Abstract
The von Hippel-Lindau tumor suppressor protein (pVHL) is a substrate receptor for the mammalian SCF-2 E3 ubiquitin ligase complex that targets several substrates for ubiquitination and proteasomal degradation. Among these targets are the α-regulatory subunits of the hypoxia-inducible factor (HIF). VHL−/− cells constitutively overexpress hypoxia-inducible genes through both transcriptional and posttranscriptional mechanisms and form tumors when injected into nude mice. Reintroduction of pVHL into VHL−/− cell lines restores normal oxygen-dependent regulation of these genes and suppresses tumor formation in the mouse xenograft assay. We report here that short hairpin RNA-mediated inactivation of HIF phenocopies the effects of pVHL reintroduction with respect to decreased expression of hypoxia-inducible genes, decreased ability to promote vascular endothelial cell proliferation in vitro, and tumor growth suppression in vivo. In addition, HIF inactivation abrogated the cellular response to hypoxia, indicating that HIF is the only pVHL target required for this response. These data suggest that deregulation of hypoxia-inducible genes in VHL−/− cells can be attributed mainly to deregulation of HIF and validate HIF as a therapeutic anticancer drug target.
Efficient Down-Regulation of Cyclin A-Associated Activity and Expression in Suspended Primary Keratinocytes Requires p21Cip1
Authors: Hauser Paul , Ma Le , Agrawal Deepak , Haura Eric , Cress W. Douglas , Pledger W. Jackson 
Published: May 2022

Abstract
When suspended in methylcellulose, primary mouse keratinocytes cease proliferation and differentiate. Suspension also reduces the activity of the cyclin-dependent kinase cdk2, an important cell cycle regulatory enzyme. To determine how suspension modulates these events, we examined its effects on wild-type keratinocytes and keratinocytes nullizygous for the cdk2 inhibitor p21Cip1. After suspension of cycling cells, amounts of cyclin A (a cdk2 partner), cyclin A mRNA, and cyclin A-associated activity decreased much more rapidly in the presence than in the absence of p21Cip1. Neither suspension nor p21Cip1 status affected the stability of cyclin A mRNA. Loss of p21Cip1 reduced the capacity of suspended cells to growth arrest, differentiate, and accumulate p27Kip1 (a second cdk2 inhibitor) and affected the composition of E2F DNA binding complexes. Cyclin A-cdk2 complexes in suspended p21+/+ cells contained p21Cip1 or p27Kip1, whereas most of the cyclin A-cdk2 complexes in p21−/− cells lacked p27Kip1. Ectopic expression of p21Cip1 allowed p21−/− keratinocytes to efficiently down-regulate cyclin A and differentiate when placed in suspension. These findings show that p21Cip1 mediates the effects of suspension on numerous processes in primary keratinocytes including cdk2 activity, cyclin A expression, cell cycle progression, and differentiation.
Silent Infarcts, White Matter Integrity, and Oxygen Metabolic Stress in Young Adults With and Without Sickle Cell Trait
Authors: Wang Yan , Guilliams Kristin P. , Fields Melanie E. , Fellah Slim , Binkley Michael M. , Reis Martin , Vo Katie D. , Chen Yasheng , Ying Chunwei , Blinder Morey , King Allison A. , Hulbert Monica L. , An Hongyu , Lee Jin-Moo , Ford Andria L. 
Published: May 2022

Background:
Individuals with sickle cell anemia have heightened risk of stroke and cognitive dysfunction. Given its high prevalence globally, whether sickle cell trait (SCT) is a risk factor for neurological injury has been of interest; however, data have been limited. We hypothesized that young, healthy adults with SCT would show normal cerebrovascular structure and hemodynamic function.

Methods:
As a case-control study, young adults with (N=25, cases) and without SCT (N=24, controls) underwent brain magnetic resonance imaging to quantify brain volume, microstructural integrity (fractional anisotropy), silent cerebral infarcts (SCI), intracranial stenosis, and aneurysms. Pseudocontinuous arterial spin labeling and asymmetric spin echo sequences measured cerebral blood flow and oxygen extraction fraction, respectively, from which cerebral metabolic oxygen demand was calculated. Imaging metrics were compared between SCT cases and controls. SCI volume was correlated with baseline characteristics.

Results:

Compared with controls, adults with SCT demonstrated similar normalized brain volumes (SCT 0.80 versus control 0.81,
P
=0.41), white matter fractional anisotropy (SCT 0.41 versus control 0.43,
P
=0.37), cerebral blood flow (SCT 62.04 versus control, 61.16 mL/min/100 g,
P
=0.67), oxygen extraction fraction (SCT 0.27 versus control 0.27,
P
=0.31), and cerebral metabolic oxygen demand (SCT 2.71 versus control 2.70 mL/min/100 g,
P
=0.96). One per cohort had an intracranial aneurysm. None had intracranial stenosis. The SCT cases and controls showed similar prevalence and volume of SCIs; however, in the subset of participants with SCIs, the SCT cases had greater SCI volume versus controls (0.29 versus 0.07 mL,
P
=0.008). Of baseline characteristics, creatinine was mildly elevated in the SCT cohort (0.9 versus 0.8 mg/dL,
P
=0.053) and correlated with SCI volume (ρ=0.49,
P
=0.032). In the SCT cohort, SCI distribution was similar to that of young adults with sickle cell anemia.

Conclusions:
Adults with SCT showed normal cerebrovascular structure and hemodynamic function. These findings suggest that healthy individuals with SCT are unlikely to be at increased risk for early or accelerated ischemic brain injury.
Automatic Segmentation in Acute Ischemic Stroke: Prognostic Significance of Topological Stroke Volumes on Stroke Outcome
Authors: Wong Kelvin K. , Cummock Jonathon S. , Li Guihua , Ghosh Rahul , Xu Pingyi , Volpi John J. , Wong Stephen T.C. 
Published: May 2022

Background:
Stroke infarct volume predicts patient disability and has utility for clinical trial outcomes. Accurate infarct volume measurement requires manual segmentation of stroke boundaries in diffusion-weighted magnetic resonance imaging scans which is time-consuming and subject to variability. Automatic infarct segmentation should be robust to rotation and reflection; however, prior work has not encoded this property into deep learning architecture. Here, we use rotation-reflection equivariance and train a deep learning model to segment stroke volumes in a large cohort of well-characterized patients with acute ischemic stroke in different vascular territories.

Methods:
In this retrospective study, patients were selected from a stroke registry at Houston Methodist Hospital. Eight hundred seventy-five patients with acute ischemic stroke in any brain area who had magnetic resonance imaging with diffusion-weighted imaging were included for analysis and split 80/20 for training/testing. Infarct volumes were manually segmented by consensus of 3 independent clinical experts and cross-referenced against radiology reports. A rotation-reflection equivariant model was developed based on U-Net and grouped convolutions. Segmentation performance was evaluated using Dice score, precision, and recall. Ninety-day modified Rankin Scale outcome prediction was also evaluated using clinical variables and segmented stroke volumes in different brain regions.

Results:
Segmentation model Dice scores are 0.88 (95% CI, 0.87–0.89; training) and 0.85 (0.82–0.88; testing). The modified Rankin Scale outcome prediction AUC using stroke volume in 30 refined brain regions based upon modified Rankin Scale-relevance areas adjusted for clinical variables was 0.80 (0.76–0.83) with an accuracy of 0.75 (0.72–0.78).

Conclusions:
We trained a deep learning model with encoded rotation-reflection equivariance to segment acute ischemic stroke lesions in diffusion- weighted imaging using a large data set from the Houston Methodist stroke center. The model achieved competitive performance in 175 well-balanced hold-out testing cases that include strokes from different vascular territories. Furthermore, the location specific stroke volume segmentations from the deep learning model combined with clinical factors demonstrated high AUC and accuracy for 90-day modified Rankin Scale in an outcome prediction model.
Soldiers' Dilemma: Foreign Military Training and Liberal Norm Conflict
Authors: Joyce Renanah Miles 
Published: May 2022

Abstract
The United States regularly seeks to promote the liberal norms of respect for human rights and deference to civilian authority in the militaries that it trains. Yet norm-abiding behavior often does not follow from liberal foreign military training. Existing explanations ascribe norm violations either to insufficient socialization or to interest misalignment between providers and recipients. One reason violations occur is because liberal training imparts conflicting norms. How do militaries respond when they confront the dilemma of conflict between the liberal norms of respect for human rights and civilian control of the military? The U.S. policy expectation is that trained militaries will prioritize human rights over obedience to civilian authorities. But when liberal norms clash, soldiers fall back on a third norm of cohesion, which refers to the bonds that enable military forces to operate in a unified, group- and missionoriented way. Cohesion functions as both a military norm (particularly at the individual level) and an interest (particularly at the institutional level). If a military prioritizes cohesion, then it will choose the path that best serves its organization, which may entail violating human rights, civilian control, or both. An exploration of the effects of norm conflict on military attitudes among the Armed Forces of Liberia uses an experiment embedded in a survey to probe the theory. Results provide preliminary evidence that norm conflict weakens support for human rights and democracy. Results are strongest among soldiers with more U.S. training.
Decline and Disintegration: National Status Loss and Domestic Conflict in Post-Disaster Spain
Authors: Ward Steven 
Published: May 2022

Abstract
Decline has long been a central concern of international relations scholarship, but analysts have only recently begun to investigate whether a change in international status influences a state's domestic politics. A new theoretical framework for understanding the domestic political consequences of relative national decline posits that eroding national status activates two sets of social psychological dynamics that contribute to domestic conflict inside declining states. First, eroding state status prompts some groups to strengthen their commitment to the state's status and dominant national identity, at the same time as it prompts other groups to disidentify from the state. Second, eroding status produces incentives for substate actors to derogate and scapegoat one another. These dynamics are particularly likely to contribute to center-periphery conflict in multinational states after instances of acute status loss. The plausibility of the argument is demonstrated by showing how the erosion of Spain's status (especially because of military failure in the 1898 Spanish-American War and the subsequent loss of its last colonies in the Americas) intensified domestic conflict in Spain during the first decades of the twentieth century. Findings indicate that decline may actually exacerbate domestic conflict, making it more difficult for states to adopt appropriate reforms.
The Response of a Baroclinic Anticyclonic Eddy to Relative Wind Stress Forcing
Authors: Wilder Thomas , Zhai Xiaoming , Munday David , Joshi Manoj 
Published: May 2022

Abstract
Including the ocean surface current in the calculation of wind stress is known to damp mesoscale eddies through a negative wind power input and have potential ramifications for eddy longevity. Here, we study the spindown of a baroclinic anticyclonic eddy subject to absolute (no ocean surface current) and relative (including ocean surface current) wind stress forcing by employing an idealized high-resolution numerical model. Results from this study demonstrate that relative wind stress dissipates surface mean kinetic energy (MKE) and also generates additional vertical motions throughout the whole water column via Ekman pumping. Wind stress curl–induced Ekman pumping generates additional baroclinic conversion (mean potential to mean kinetic energy) that is found to offset the damping of surface MKE by increasing deep MKE. A scaling analysis of relative wind stress–induced baroclinic conversion and relative wind stress damping confirms these numerical findings, showing that additional energy conversion counteracts relative wind stress damping. What is more, wind stress curl–induced Ekman pumping is found to modify surface potential vorticity gradients that lead to an earlier destabilization of the eddy. Therefore, the onset of eddy instabilities and eventual eddy decay takes place on a shorter time scale in the simulation with relative wind stress.
Crystal chemistry and origin of REE-bearing mukhinite from carbonate veins of the Svetlinsky gold deposit, South Urals, Russia
Authors: Korinevsky Victor G. , Chukanov Nikita V. , Aksenov Sergey M. , Korinevsky Evgeniy V. , Kotlyarov Vasiliy A. , Zamyatin Dmitry А. , Ryanskaya Anastasiya D. , Kolisnichenko Sergey V. , Lebedeva Svetlana M. , Ermolaeva Vera N. 
Published: May 2022

AbstractA rare earth element (REE)-, Cr- and Mg-bearing variety of the vanadium epidote-group mineral mukhinite occurs in a calcite–dolomite carbonatite dyke cutting metamorphosed volcano-sedimentary rocks exposed in the walls of the quarry of the Svetlinsky gold deposit, South Urals. This mineral was found in a paragene assemblage including native sulphur, phlogopite and fluorophlogopite, together with accessory pyrite, other sulfides and sulfosalts, gold, Cr- and V-bearing muscovite, margarite, Cr- and V-bearing dravite, fluoro-tremolite, actinolite, fluoro-pargasite, anhydrite, apatite, uranium hydroxides, V-rich titanite, V- and Nb-rich rutile, spinel and corundum. The contents of ΣREE2O3 and V2O3 in mukhinite vary in the ranges of 4.01–9.69 and 5.34–7.46 wt.%, respectively. A Raman spectrum of REE-rich mukhinite is provided. The main schemes of isomorphic substitutions in mukhinite are ΣREE + Mg ↔ Ca + Al and V+Cr ↔ Al. The crystal structure of REE-rich mukhinite has been studied by single-crystal X-ray diffraction analysis. The mineral is monoclinic, with the space group P21/m, and unit-cell parameters are: a = 8.8972(11) Å, b = 5.6221(6) Å, c = 10.1519(12) Å, β = 115.169° and V = 459.60(11) Å3. The crystal structure of REE-rich mukhinite is similar to that of its synthetic analogue; the refined crystal-chemical formula of the sample studied is (Z = 2): {A1CaA2(Ca0.8REE0.2)}{M1(Al0.95Cr0.05)M2AlM3[(V,Cr)3+0.40Al0.35Mg0.25]}(Si2O7)(SiO4)O(OH).
Enhancement of Electrochromic Properties of Polyaniline Induced by Copper Ions
Authors: Qin Ting , Deng Lianwen , Zhang Pin , Tang Min , Li Chen , Xie Haipeng , Huang Shengxiang , Gao Xiaohui 
Published: May 2022

AbstractDriven by the urgent need for adaptive infrared (IR) electrochromic devices, the improvement in electrochromic performance based on polyaniline (PANI) conducting polymers has become an outstanding challenge. In recent years, the acid doping strategy has been proven to increase the IR modulation ability of PANI, in particular for the Bronsted acid doping. Herein, the effects of copper ions, a Lewis acid, on the structure and electrochromic properties of polyaniline were investigated. Compared to pure polyaniline, the Cu-doped PANI porous films show better IR modulation ability. With the increasing concentration of copper ions, the Cu-doped PANI porous films exhibit a trend in volcanic patterns for the emittance variation (∆ε), depending on the number of polarons and bipolarons. The optimal IR emissivity (ε) modulation obtained on Cu-doped PANI films shows the ∆ε modulation of 0.35 and 0.3 in the wavelength range of 8–14 µm and 2.5–25 µm, superior to previously reported pure sulfuric acid-doped PANI. Furthermore, a flexible IR electrochromic device was fabricated with the present Cu-doped PANI porous films. The modulation of the emittance variation varied between 0.513 and 0.834 (∆ε = 0.32 in ranges of wavelength 8–12 µm), suggesting the great potential for applications in military camouflage and intelligent IR thermal management. We believe that the results in this work will provide a novel perspective and avenue for improving the IR modulation ability of electrochromic devices based on polyaniline conducting polymers.
Design of GAA Nanosheet Ferroelectric Area Tunneling FET and Its Significance with DC/RF Characteristics Including Linearity Analyses
Authors: Thoti Narasimhulu , Li Yiming 
Published: May 2022

AbstractThis work reports an emerging structure of gate-all-around ferroelectric area tunneling field-effect transistor (FATFET) by considering ferroelectric and a n-epitaxial layer enveloped around the overlapped region of the source and channel to succeed with complete area of tunneling probability. To accomplish this, ferroelectric ($$\hbox{Hf}_{0.5}\hbox{Zr}_{0.5}\hbox{O}_2$$

Hf

0.5

Zr

0.5

O
2

) is exploited and modeled to boost the FATFET performance through internal-voltage ($$V_{{\rm int}}$$

V
int

) amplification. The corresponding modeling approach to estimate the ferroelectric parameters along with $$V_{{\rm int}}$$

V
int

calculations of the metal-ferroelectric-insulator (MFIS) option through capacitance equivalent method is addressed. Using these options the proposed device outperforms effectively in delivering superior DC and RF performance among possible options of the $$\hbox{Si}_{1-x}\hbox{Ge}_x$$

Si

1
-
x

Ge
x

ferroelectric TFETs. The significance of proposed design is examined with recently reported ferroelectric TFETs. Our results show 10-time advancement on the $$I_{{\rm on}}$$

I
on

, reduced steep or average subthreshold swing (< 25 mV/dec), frequencies higher than 150 GHz, and insignificant to linearity deviations at low bias points. Furthermore, 2-order reduction in energy efficiency is succeeded with the proposed design environment.
Hsa_circ_0000345 inhibits cell proliferation, migration and invasion of nasopharyngeal carcinoma cells via miR-513a-3p/PTEN axis
Authors: Jiang Chang , Li Hongyan , Liu Fei , Shi Linggai , Liu Jun , Li Yujie 
Published: May 2022

Abstract
Background
Hsa_circ_0000345 has been reported to be down-regulated in nasopharyngeal carcinoma (NPC). Whether hsa_circ_0000345 can exert antitumor effect in NPC remains unclear. This study aimed to investigate the possible biological role of hsa_cic_0000345 in suppressing the progression of NPC.

Methods
Hsa_circ_0000345 expression was detected in normal nasopharynx epithelial cells (NP69) and NPC cell lines (SUNE1, HONE1, 6-10B and HNE1). The influence of hsa_circ_0000345 on cell proliferation, migration and invasion of NPC cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays. Quantitative real-time PCR and western blot were performed to examine gene and protein expression, respectively. Luciferase reporter assay was carried out to verify the relationship among hsa_circ_0000345, miR-513a-3p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN).

Results
Compared with NP69 cells, hsa_circ_0000345 was down-regulated in NPC cells. Moreover, hsa_circ_0000345 overexpression repressed cell proliferation, migration and invasion of SUNE1 cells, whereas hsa_circ_0000345 knockdown promoted cell proliferation, migration and invasion of 6-10B cells. Furthermore, hsa_circ_0000345 promoted PTEN expression by sponging miR-513a-3p. Both miR-513a-3p overexpression and PTEN knockdown promoted cell proliferation, migration and invasion of SUNE1 cells, which were effectively abolished by hsa_circ_0000345 up-regulation.

Conclusion
Hsa_circ_0000345 inhibits cell proliferation, migration and invasion of NPC cells via miR-513a-3p/PTEN axis, thereby suppressing the progression of NPC. Thus, this work suggests that hsa_circ_0000345 may be a potential biomarker for diagnosis and treatment of NPC.