bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-related changes in the effects of strength training on lower leg muscles in healthy individuals measured using MRI
Authors: Psatha Maria , Wu Zhiqing , Gammie Fiona , Ratkevicius Aivaras , Wackerhage Henning , Redpath Thomas W , Gilbert Fiona J , Meakin Judith R , Aspden Richard M 
Published: July 2017

BackgroundWe previously measured the rate of regaining muscle strength during rehabilitation of lower leg muscles in patients following lower leg casting. Our primary aim in this study was to measure the rate of gain of strength in healthy individuals undergoing a similar training regime. Our secondary aim was to test the ability of MRI to provide a biomarker for muscle function.MethodsMen and women were recruited in three age groups: 20–30, 50–65 and over 70 years. Their response to resistance training of the right lower leg twice a week for 8 weeks was monitored using a dynamometer and MRI of tibialis anterior, soleus and gastrocnemius muscles at 2 weekly intervals to measure muscle size (anatomical cross-sectional area (ACSA)) and quality (T2relaxation). Forty-four volunteers completed the study.ResultsBaseline strength declined with age. Training had no effect in middle-aged females or in elderly men in dorsiflexion. Other groups significantly increased both plantarflexion and dorsiflexion strength at rates up to 5.5 N m week-1in young females in plantarflexion and 1.25 N m week-1in young males in dorsiflexion. No changes were observed inACSAorT2in any age group in any muscle.ConclusionExercise training improves muscle strength in males at all ages except the elderly in dorsiflexion. Responses in females were less clear with variation across age and muscle groups. These results were not reflected in simple MRI measures that do not, therefore, provide a good biomarker for muscle atrophy or the efficacy of rehabilitation.
Spherical orbifold tutte embeddings
Authors: Aigerman Noam , Kovalsky Shahar Z. , Lipman Yaron 
Published: July 2017

This work presents an algorithm for injectively parameterizing surfaces into spherical target domains called spherical orbifolds. Spherical orbifolds are cone surfaces that are generated from symmetry groups of the sphere. The surface is mapped the spherical orbifold via an extension of Tutte's embedding. This embedding is proven to be bijective under mild additional assumptions, which hold in all experiments performed.
This work also completes the adaptation of Tutte's embedding to orbifolds of the three classic geometries - Euclidean, hyperbolic and spherical - where the first two were recently addressed.
The spherical orbifold embeddings approximate conformal maps and require relatively low computational times. The constant positive curvature of the spherical orbifolds, along with the flexibility of their cone angles, enables producing embeddings with lower isometric distortion compared to their Euclidean counterparts, a fact that makes spherical orbifolds a natural candidate for surface parameterization.
Similarity maps and field-guided T-splines
Authors: Campen Marcel , Zorin Denis 
Published: July 2017

A variety of techniques were proposed to model smooth surfaces based on tensor product splines (e.g. subdivision surfaces, free-form splines, T-splines). Conversion of an input surface into such a representation is commonly achieved by constructing a global seamless parametrization, possibly aligned to a guiding cross-field (e.g. of principal curvature directions), and using this parametrization as domain to construct the spline-based surface.
One major fundamental difficulty in designing robust algorithms for this task is the fact that for common types, e.g. subdivision surfaces (requiring a conforming domain mesh) or T-spline surfaces (requiring a globally consistent knot interval assignment) reliably obtaining a suitable parametrization that has the same topological structure as the guiding field poses a major challenge. Even worse, not all fields do admit suitable parametrizations, and no concise conditions are known as to which fields do.

We present a class of surface constructions (T-splines with
halfedge knots
) and a class of parametrizations (
seamless similarity maps
) that are, in a sense, a perfect match for the task: for
any
given guiding field structure, a compatible parametrization of this kind exists and a smooth piecewise rational surface with exactly the same structure as the input field can be constructed from it. As a byproduct, this enables full control over extraordinary points. The construction is backward compatible with classical NURBS. We present efficient algorithms for building discrete conformal similarity maps and associated T-meshes and T-spline surfaces.
Constrained palette-space exploration
Authors: Mellado Nicolas , Vanderhaeghe David , Hoarau Charlotte , Christophe Sidonie , Brédif Mathieu , Barthe Loic 
Published: July 2017

Color palettes are widely used by artists to define colors of artworks and explore color designs. In general, artists select the colors of a palette by following a set of rules, e.g. contrast or relative luminance. Existing interactive palette exploration tools explore palette spaces following limited constraints defined as geometric configurations in color space e.g. harmony rules on the color wheel. Palette search algorithms sample palettes from color relations learned from an input dataset, however they cannot provide interactive user edits and palette refinement.
We introduce in this work a new versatile formulation enabling the creation of constraint-based interactive palette exploration systems. Our technical contribution is a graph-based palette representation, from which we define palette exploration as a minimization problem that can be solved efficiently and provide real-time feedback. Based on our formulation, we introduce two interactive palette exploration strategies: constrained palette exploration, and for the first time, constrained palette interpolation. We demonstrate the performances of our approach on various application cases and evaluate how it helps users finding trade-offs between concurrent constraints.
Robust eXtended finite elements for complex cutting of deformables
Authors: Koschier Dan , Bender Jan , Thuerey Nils 
Published: July 2017

In this paper we present a robust remeshing-free cutting algorithm on the basis of the eXtended Finite Element Method (XFEM) and fully implicit time integration. One of the most crucial points of the XFEM is that integrals over discontinuous polynomials have to be computed on subdomains of the polyhedral elements. Most existing approaches construct a cut-aligned auxiliary mesh for integration. In contrast, we propose a cutting algorithm that includes the construction of specialized quadrature rules for each dissected element without the requirement to explicitly represent the arising subdomains. Moreover, we solve the problem of ill-conditioned or even numerically singular solver matrices during time integration using a novel algorithm that constrains non-contributing degrees of freedom (DOFs) and introduce a preconditioner that efficiently reuses the constructed quadrature weights.Our method is particularly suitable for fine structural cutting as it decouples the added number of DOFs from the cut's geometry and correctly preserves geometry and physical properties by accurate integration. Due to the implicit time integration these fine features can still be simulated robustly using large time steps. As opposed to this, the vast majority of existing approaches either use remeshing or element duplication. Remeshing based methods are able to correctly preserve physical quantities but strongly couple cut geometry and mesh resolution leading to an unnecessary large number of additional DOFs. Element duplication based approaches keep the number of additional DOFs small but fail at correct conservation of mass and stiffness properties. We verify consistency and robustness of our approach on simple and reproducible academic examples while stability and applicability are demonstrated in large scenarios with complex and fine structural cutting.
Enhanced NO-dependent pulmonary vasodilation limits increased vasoconstrictor sensitivity in neonatal chronic hypoxia
Authors: Sheak Joshua R. , Weise-Cross Laura , deKay Ray J. , Walker Benjimen R. , Jernigan Nikki L. , Resta Thomas C. 
Published: July 2017

Augmented vasoconstrictor reactivity is thought to play an important role in the development of chronic hypoxia (CH)-induced neonatal pulmonary hypertension. However, whether this response to CH results from pulmonary endothelial dysfunction and reduced nitric oxide (NO)-mediated vasodilation is not well understood. We hypothesized that neonatal CH enhances basal tone and pulmonary vasoconstrictor sensitivity by limiting NO-dependent pulmonary vasodilation. To test this hypothesis, we assessed the effects of the NO synthase (NOS) inhibitor Nω-nitro-l-arginine (l-NNA) on baseline pulmonary vascular resistance (PVR) and vasoconstrictor sensitivity to the thromboxane mimetic U-46619 in saline -perfused lungs (in situ) from 2-wk-old control and CH (12-day exposure, 0.5 atm) Sprague-Dawley rats. Basal tone was defined as that reversed by exogenous NO (spermine NONOate). CH neonates displayed elevated right ventricular systolic pressure (in vivo) and right ventricular hypertrophy, indicative of pulmonary hypertension. Perfused lungs from CH rats demonstrated greater baseline PVR, basal tone, and U-46619-mediated vasoconstriction compared with control rats in the absence of l-NNA. l-NNA markedly increased baseline PVR and reactivity to U-46619 in lungs from CH neonates, further augmenting vasoconstrictor sensitivity compared with control lungs. Exposure to CH also enhanced NO-dependent vasodilation to arginine vasopressin, pulmonary expression of NOS III [endothelial NOS (eNOS)], and eNOS phosphorylation at activation residue Ser1177. However, CH did not alter lung nitrotyrosine levels, a posttranslational modification reflecting [Formula: see text] scavenging of NO. We conclude that, in contrast to our hypothesis, enhanced basal tone and agonist-induced vasoconstriction after neonatal CH is limited by increased NO-dependent pulmonary vasodilation resulting from greater eNOS expression and phosphorylation at activation residue Ser1177. NEW & NOTEWORTHY This research is the first to demonstrate enhanced nitric oxide-dependent vasodilation that limits increased vasoconstrictor reactivity in neonatal pulmonary hypertension. These results suggest that augmented vasoconstriction in this setting reflects changes in smooth muscle reactivity rather than a reduction in nitric oxide-dependent pulmonary vasodilation.
Mineralocorticoid receptor antagonists attenuate exaggerated exercise pressor reflex responses in hypertensive rats
Authors: Downey Ryan M. , Mizuno Masaki , Mitchell Jere H. , Vongpatanasin Wanpen , Smith Scott A. 
Published: July 2017

Exaggerated heart rate (HR) and blood pressure responses to exercise in hypertension are mediated, in part, by overactivity of the exercise pressor reflex (EPR). The mechanisms underlying this EPR dysfunction have not been fully elucidated. Previous studies have shown that stimulation of mineralocorticoid receptors (MRs) with exogenous administration of aldosterone in normal, healthy rats reproduces the EPR overactivity characteristic of hypertensive animals. Conversely, the purpose of this study was to examine whether antagonizing MR with spironolactone (SPIR) or eplerenone (EPL) in decerebrated hypertensive rats ameliorates abnormal EPR function. Changes in mean arterial pressure (MAP) and HR induced by EPR or muscle mechanoreflex (a component of EPR) activation were assessed in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) fed normal chow (NC) or a customized diet containing either SPIR or EPL for 3 wk. SHRs treated with SPIR or EPL had significantly attenuated MAP responses to EPR (NC: 45 ± 7 mmHg, SPIR: 26 ± 4 mmHg, and EPL: 24 ± 5 mmHg, P = 0.02) and mechanoreflex (NC: 34 ± 9 mmHg, SPIR: 17 ± 3 mmHg, and EPL: 15 ± 3 mmHg, P = 0.03) activation. SHRs treated with SPIR or EPL also showed significantly attenuated HR responses to EPR (NC: 17 ± 3 beats/min, SPIR: 9 ± 1 beats/min, and EPL: 9 ± 2 beats/min, P = 0.01) and mechanoreflex (NC: 15 ± 3 beats/min, SPIR: 6 ± 1 beats/min, and EPL: 7 ± 1 beats/min, P = 0.01) activation. Wistar-Kyoto rats treated with SPIR did not demonstrate significant differences in MAP or HR responses to EPR or mechanoreflex activation. The data suggest that antagonizing MRs may be an effective strategy for the treatment of EPR overactivity in hypertension. NEW & NOTEWORTHY Exaggerated cardiovascular responses to exercise in hypertensive patients are linked with overactive exercise pressor reflexes (EPRs). Administration of low-dose mineralocorticoid receptor antagonists (spironolactone or eplerenone) effectively ameliorates abnormal EPR function in hypertension. Effective treatment of EPR overactivity may reduce the cardiovascular risks associated with physical activity in hypertension.
Tumorigenic Heterogeneity in Cancer Stem Cells Evolved from Long-term Cultures of Telomerase-Immortalized Human Mesenchymal Stem Cells
Authors: Burns Jorge S. , Abdallah Basem M. , Guldberg Per , Rygaard Jørgen , Schrøder Henrik D. , Kassem Moustapha 
Published: July 2017

Abstract
Long-term cultures of telomerase-transduced adult human mesenchymal stem cells (hMSC) may evolve spontaneous genetic changes leading to tumorigenicity in immunodeficient mice (e.g., hMSC-TERT20). We wished to clarify whether this unusual phenotype reflected a rare but dominant subpopulation or if the stem cell origin allowed most cells to behave as cancer stem cells. Cultures of the hMSC-TERT20 strain at population doubling 440 were highly clonogenic (94%). From 110 single-cell clones expanded by 20 population doublings, 6 underwent detailed comparison. Like the parental population, each clone had ≈1.2 days doubling time with loss of contact inhibition. All retained 1,25-(OH)2 vitamin D3–induced expression of osteoblastic markers: collagen type I, alkaline phosphatase, and osteocalcin. All shared INK4a/ARF gene locus deletion and epigenetic silencing of the DBCCR1 tumor suppressor gene. Despite in vitro commonality, only four of six clones shared the growth kinetics and 100% tumorigenicity of the parental population. In contrast, one clone consistently formed latent tumors and the other established tumors with only 30% penetrance. Changing the in vitro microenvironment to mimic in vivo growth aspects revealed concordant clonal heterogeneity. Latent tumor growth correlated with extracellular matrix entrapment of multicellular spheroids and high procollagen type III expression. Poor tumorigenicity correlated with in vitro serum dependence and high p27Kip1 expression. Aggressive tumorigenicity correlated with good viability plus capillary morphogenesis on serum starvation and high cyclin D1 expression. Thus, hMSC-TERT20 clones represent cancer stem cells with hierarchical tumorigenicity, providing new models to explore the stem cell hypothesis for cancer.
Phenoxodiol, a Novel Isoflavone, Induces G1 Arrest by Specific Loss in Cyclin-Dependent Kinase 2 Activity by p53-Independent Induction of p21WAF1/CIP1
Authors: Aguero Martin F. , Facchinetti Maria M. , Sheleg Zhanna , Senderowicz Adrian M. 
Published: July 2017

AbstractPhenoxodiol, an isoflavone derivative of genistein with unknown mechanism of action, is currently being evaluated in early human cancer clinical trials. To determine the mechanism of antiproliferative effects of phenoxodiol, we examined its effects in a battery of human cell lines. Although we observed caspase-dependent apoptosis in HN12 cells as early as 24 hours after exposure, clonogenic death occurred only after 48-hour exposure despite caspase blockade by the general caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (ZVAD)-fmk. Moreover, clear evidence of cell death as determined by nuclear morphology and plasmatic membrane damage occur despite ZVAD, suggesting that another mechanism besides caspase-dependent apoptosis is required for clonogenic death induced by phenoxodiol. In search for other potential antiproliferative effects, we assessed the effects of phenoxodiol in the cell cycle progression of human carcinoma cell lines. A significant G1-S arrest was observed by 12 hours of exposure in HN12 cell lines at concentrations ≥5 μg/mL. Cell cycle arrest occurred several hours (∼12 hours) before induction of apoptosis. Analysis of in vitro purified cyclin-dependent kinase (cdk) activity showed that phenoxodiol did not inhibit cdk activity. In contrast, cellular cdk2 activity obtained from HN12 cell lines exposed to phenoxodiol for 12 hours decreased by 60%, whereas cdk6 activity remained unaltered, suggesting that the loss of cdk2 activity was specific. Loss in cdk2 activity was preceded by the accumulation of the endogenous cdk inhibitor p21WAF1. To assess the role of p21WAF1 induction by phenoxodiol, we used HCT116 isogenic cell lines and showed that phenoxodiol induced G1 arrest together with p21WAF1 expression in wild-type clones. In contrast, p21−/− variants failed to show G1 arrest. Finally, induction of p21 by phenoxodiol is p53 independent, as phenoxodiol induced p21 in HCT116 lacking p53. These data therefore indicate that phenoxodiol promotes G1-S arrest by the specific loss in cdk2 activity due to p53-independent p21WAF1 induction. This novel feature of phenoxodiol may have clinical implications, as the majority of human malignancies have aberrations in cell cycle progression regulation.
C-C Chemokine Receptor 5 on Stromal Cells Promotes Pulmonary Metastasis
Authors: van Deventer Hendrik W. , O'Connor William , Brickey W. June , Aris Robert M. , Ting Jenny P.Y. , Serody Jonathan S. 
Published: July 2017

AbstractWe have shown that mice that express the C-C chemokine receptor 5 (CCR5) have enhanced local tumor growth and an impaired response to vaccine therapy compared with CCR5 knockout (CCR5−/−) mice. Here, we extend these observations to evaluate the function of CCR5 in pulmonary metastasis and the mechanism underlying the diminished tumor growth in CCR5−/− mice. Lung metastases were counted in wild-type (WT) and CCR5−/− mice following the injection of 1 × 106 B16-F10 melanoma cells. These results were compared with those from syngeneic bone marrow chimeric mice formed by the transfer of WT bone marrow into irradiated CCR5−/− and CCR5−/− marrow into irradiated WT mice. Intact CCR5−/− mice developed fewer metastases than WT mice (40.2 versus 70.6; P &lt; 0.05). Bone marrow chimeras formed by the transfer of WT bone marrow into CCR5−/− hosts had fewer metastases than WT hosts injected with knockout marrow (46.6 versus 98.6; P &lt; 0.01). Adoptive transfer of CCR5-expressing leukocytes also failed to promote metastasis in CCR5−/− mice. However, the i.v. transfer of WT pulmonary stromal cells into CCR5−/− mice increased the number of metastases compared with transfer of CCR5−/− stromal cells (102.8 versus 26.0; P &lt; 0.05). These results show for the first time that CCR5 expression on stromal and not hematopoietic cells contributes to tumor metastasis. Therefore, recently developed CCR5 inhibitors may have a novel benefit in cancer therapy.
Target Cell–Restricted Apoptosis Induction of Acute Leukemic T Cells by a Recombinant Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Fusion Protein with Specificity for Human CD7
Authors: Bremer Edwin , Samplonius Douwe F. , Peipp Matthias , van Genne Linda , Kroesen Bart-Jan , Fey Georg H. , Gramatzki Martin , de Leij Lou F.M.H. , Helfrich Wijnand 
Published: July 2017

AbstractCurrent treatment of human T-cell leukemia and lymphoma is predominantly limited to conventional cytotoxic therapy and is associated with limited therapeutic response and significant morbidity. Therefore, more potent and leukemia-specific therapies with favorable toxicity profiles are urgently needed. Here, we report on the construction of a novel therapeutic fusion protein, scFvCD7:sTRAIL, designed to induce target antigen-restricted apoptosis in human T-cell tumors. ScFvCD7:sTRAIL consists of the death-inducing tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) genetically linked to an scFv antibody fragment specific for the T-cell surface antigen CD7. Treatment with scFvCD7:sTRAIL induced potent CD7-restricted apoptosis in a series of malignant T-cell lines, whereas normal resting leukocytes, activated T cells, and vascular endothelial cells (human umbilical vein endothelial cells) showed no detectable apoptosis. The apoptosis-inducing activity of scFvCD7:sTRAIL was stronger than that of the immunotoxin scFvCD7:ETA. In mixed culture experiments with CD7-positive and CD7-negative tumor cells, scFvCD7:sTRAIL induced very potent bystander apoptosis of CD7-negative tumor cells. In vitro treatment of blood cells freshly derived from T-acute lymphoblastic leukemia patients resulted in marked apoptosis of the malignant T cells that was strongly augmented by vincristin. In conclusion, scFvCD7:sTRAIL is a novel recombinant protein causing restricted apoptosis in human leukemic T cells with low toxicity for normal human blood and endothelial cells.
The Serine/Threonine Protein Kinase, p90 Ribosomal S6 Kinase, Is an Important Regulator of Prostate Cancer Cell Proliferation
Authors: Clark D.E. , Errington T.M. , Smith J.A. , Frierson H.F. , Weber M.J. , Lannigan D.A. 
Published: July 2017

AbstractAn increase in the activity of mitogen-activated protein kinase (MAPK) has been correlated with the progression of prostate cancer to advanced disease in humans. The serine/threonine protein kinase p90-kDa ribosomal S6 kinase (RSK) is an important downstream effector of MAPK but its role in prostate cancer has not previously been examined. Increasing RSK isoform 2 (RSK2) levels in the human prostate cancer line, LNCaP, enhanced prostate-specific antigen (PSA) expression, an important diagnostic marker for prostate cancer, whereas inhibiting RSK activity using a RSK-specific inhibitor, 3Ac-SL0101, decreased PSA expression. The RSK2 regulation of PSA expression occurred via a mechanism involving both RSK2 kinase activity and its ability to associate with the coactivator, p300. RNA interference of the androgen receptor (AR) showed that the AR was important in the RSK2-mediated increase in PSA expression. RSK levels are higher in ∼50% of human prostate cancers compared with normal prostate tissue, which suggests that increased RSK levels may participate in the rise in PSA expression that occurs in prostate cancer. Furthermore, 3Ac-SL0101 inhibited proliferation of the LNCaP line and the androgen-independent human prostate cancer line, PC-3. These results suggest that proliferation of some prostate cancer cells is dependent on RSK activity and support the hypothesis that RSK may be an important chemotherapeutic target for prostate cancer.