bluuebunny/crossref_metadata_2025 huggingface dataset:
CIRCE: The Canarias InfraRed Camera Experiment for the Gran Telescopio Canarias
Authors: Eikenberry Stephen S. , Charcos Miguel , Edwards Michelle L. , Garner Alan , Lasso-Cabrera Nestor , Stelter Richard D. , Marin-Franch Antonio , Raines S. Nicholas , Ackley Kendall , Bennett John G. , Cenarro Javier A. , Chinn Brian , Donoso H. Veronica , Frommeyer Raymond , Hanna Kevin , Herlevich Michael D. , Julian Jeff , Miller Paola , Mullin Scott , Murphey Charles H. , Packham Chris , Varosi Frank , Vega Claudia , Warner Craig , Ramaprakash A. N. , Burse Mahesh , Punnadi Sunjit , Chordia Pravin , Gerarts Andreas , Martín Héctor de Paz , Calero María Martín , Scarpa Riccardo , Acosta Sergio Fernandez , Sánchez William Miguel Hernández , Siegel Benjamin , Pérez Francisco Francisco , Martín Himar D. Viera , Losada José A. Rodríguez , Nuñez Agustín , Tejero Álvaro , González Carlos E. Martín , Rodríguez César Cabrera , Sendra Jordi Molgó , Rodriguez J. Esteban , Cáceres J. Israel Fernádez , García Luis A. Rodríguez , Lopez Manuel Huertas , Dominguez Raul , Gaggstatter Tim , Lavers Antonio Cabrera , Geier Stefan , Pessev Peter , Sarajedini Ata , Castro-Tirado A. J.
Published: February 2018

The Canarias InfraRed Camera Experiment (CIRCE) is a near-infrared (1–2.5[Formula: see text][Formula: see text]m) imager, polarimeter and low-resolution spectrograph operating as a visitor instrument for the Gran Telescopio Canarias (GTC) 10.4-m telescope. It was designed and built largely by graduate students and postdocs, with help from the University of Florida (UF) astronomy engineering group, and is funded by the UF and the US National Science Foundation. CIRCE is intended to help fill the gap in near-infrared capabilities prior to the arrival of Especrografo Multiobjecto Infra-Rojo (EMIR) to the GTC and will also provide the following scientific capabilities to compliment EMIR after its arrival: high-resolution imaging, narrowband imaging, high-time-resolution photometry, imaging polarimetry, and low resolution spectroscopy. In this paper, we review the design, fabrication, integration, lab testing, and on-sky performance results for CIRCE. These include a novel approach to the opto-mechanical design, fabrication, and alignment.
Robot Integrated User Interface for Physical Interaction with the DLR MIRO in Versatile Medical Procedures
Authors: Schlenk C. , Bahls T. , Tarassenko S. , Klodmann J. , Bihler M. , Wuesthoff T.
Published: February 2018

To enhance the capability of the DLR MIRO for physical human robot interaction (pHRI), six buttons were integrated as additional input interface along the robot structure. A ring of eight RGB-LEDs at the instrument interface informs the user as additional output interface about the robot’s state. The mechatronic design, which is transferable to other robots, adapts to the existing communication infrastructure of the robot and therefore offers real-time capability. Besides the interaction with the robot itself, it also allows the control of third party devices connected to its communication network. Both interfaces can be flexibly programmed e.g. in C++ or Simulink.
3D source-rock modelling in frontier basins: a case study from the Zambezi Delta Depression
Authors: Butt Alice J. , Gould Kathleen
Published: February 2018

Regional modelling is vital for the preliminary analysis of a basin's hydrocarbon potential, especially when working on incomplete datasets. The Zambezi Delta Depression is a frontier basin that was selected to demonstrate how limited, publically available depth data can be used to evaluate source-rock maturity and hydrocarbon expulsion using 3D basin modelling. A geological framework was built with multiple datasets correlated using a global sequence-stratigraphic model. The identification of key events in the geological history of the region and the basin geometries allowed interpretation of intervals of organic enrichment within the basin during the Bajocian, Kimmeridgian and early Aptian. The results from the pressure and temperature modelling show that these potential source-rock horizons are currently overmature to gas mature in the Zambezi Delta Depression. Using the most likely heat-flow scenario, the timing of maturity and expulsion of the potential source rocks are strongly controlled by the geometry of the basin, with ages decreasing towards the SW. Expulsion modelling suggests that the Late Cretaceous plays are most likely to be charged by the early Aptian source rock, with older potential plays charged by the Jurassic source rocks. As the heat-flow model was poorly constrained, warmer and cooler temperature scenarios were also applied to qualitatively compare the impact on maturity, expulsion and accumulation of hydrocarbons in the basin. The modelling results, when compared with sparse published data, favour the most likely and warmer scenario.

Supplementary material:
Details of the model input data, source-rock definitions and software used in this project are available at
https://doi.org/10.6084/m9.figshare.c.3970863
cGAS-mediated autophagy protects the liver from ischemia-reperfusion injury independently of STING
Authors: Lei Zhao , Deng Meihong , Yi Zhongjie , Sun Qian , Shapiro Richard A. , Xu Hongbo , Li Tunliang , Loughran Patricia A. , Griepentrog John E. , Huang Hai , Scott Melanie J. , Huang Feizhou , Billiar Timothy R.
Published: February 2018

Liver ischemia-reperfusion (I/R) injury occurs through induction of oxidative stress and release of damage-associated molecular patterns (DAMPs), including cytosolic DNA released from dysfunctional mitochondria or from the nucleus. Cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) synthase (cGAS) is a cytosolic DNA sensor known to trigger stimulator of interferon genes (STING) and downstream type 1 interferon (IFN-I) pathways, which are pivotal innate immune system responses to pathogen. However, little is known about the role of cGAS/STING in liver I/R injury. We subjected C57BL/6 (WT), cGAS knockout (cGAS−/−), and STING-deficient (STINGgt/gt) mice to warm liver I/R injury and that found cGAS−/− mice had significantly increased liver injury compared with WT or STINGgt/gt mice, suggesting a protective effect of cGAS independent of STING. Liver I/R upregulated cGAS in vivo and also in vitro in hepatocytes subjected to anoxia/reoxygenation (A/R). We confirmed a previously published finding that hepatocytes do not express STING under normoxic conditions or after A/R. Hepatocytes and liver from cGAS−/− mice had increased cell death and reduced induction of autophagy under hypoxic conditions as well as increased apoptosis. Protection could be restored in cGAS−/− hepatocytes by overexpression of cGAS or by pretreatment of mice with autophagy inducer rapamycin. Our findings indicate a novel protective role for cGAS in the regulation of autophagy during liver I/R injury that occurs independently of STING.

NEW & NOTEWORTHY Our studies are the first to document the important role of cGAS in the acute setting of sterile injury induced by I/R. Specifically, we provide evidence that cGAS protects liver from I/R injury in a STING-independent manner.
Inhibition of mucin secretion via glucocorticoid-induced regulation of calcium-related proteins in mouse lung
Authors: An Jin Yong , Ahn Changhwan , Kang Hee Young , Jeung Eui-Bae
Published: February 2018

Calcium is important for physiological functioning in many tissues and is essential in mucus secretion and muscle contraction. Intracellular concentrations of calcium are regulated by calcium-related proteins, such as transient receptor potential cation channel subfamily V member 4 (TRPV 4), TRPV6, Calbindin-D9k(CaBP-9k), sodium-calcium exchanger (NCX1), and plasma membrane Ca2+ATPase 1 (PMCA1). In this study, the relationship between secretion of pulmonary mucus and calcium regulation was investigated. To confirm the effect of steroid hormones, immature mice were injected with estrogen (E2) or progesterone (P4), and mature mice were injected with dexamethasone (DEX). Subsequently, the location and expression of TRPV4, TRPV6, CaBP-9k, NCX1, and PMCA1 in lung tissue were examined. Periodic acid-Schiff staining was performed to investigate functional aspects of the protein expression. There were no significant differences in calcium-related gene expression in E2- and P4-treated mice, but TRPV4, NCX1, and PMCA1 were increased in DEX-treated mice and were recovered by RU486 treatment. DEX induces the expression of calcium-related proteins through the glucocorticoid receptor-mediated pathway and may involve decreased mucin secretion in the bronchiole. TRPV4, TRPV6, CaBP-9k, NCX1, and PMCA1 were specifically expressed in Clara and alveolar type 2 cells of mouse lung. CC10, a marker of Clara cells, was decreased by DEX. In addition, mucin secretion, which is a functional aspect of this cell, was also decreased by DEX treatment. Control of calcium-related gene expression may affect the control of mucus secretion in the lung. Such a control mechanism can form the basis of studies into diseases such as inflammation attributable to mucus secretion abnormalities, coughing, and respiratory disorders and distress.
Measures of sympathetic and parasympathetic autonomic outflow from heartbeat dynamics
Authors: Valenza Gaetano , Citi Luca , Saul J. Philip , Barbieri Riccardo
Published: February 2018

Reliable and effective noninvasive measures of sympathetic and parasympathetic peripheral outflow are of crucial importance in cardiovascular physiology. Although many techniques have been proposed to take up this long-lasting challenge, none has proposed a satisfying discrimination of the dynamics of the two separate branches. Spectral analysis of heart rate variability is the most currently used technique for such assessment. Despite its widespread use, it has been demonstrated that the subdivision in the low-frequency (LF) and high-frequency (HF) bands does not fully reflect separate influences of the sympathetic and parasympathetic branches, respectively, mainly due to their simultaneous action in the LF. Two novel heartbeat-derived autonomic measures, the sympathetic activity index (SAI) and parasympathetic activity index (PAI), are proposed to separately assess the time-varying autonomic nervous system synergic functions. Their efficacy is validated in landmark autonomic maneuvers generally employed in clinical settings. The novel measures move beyond the classical frequency domain paradigm through identification of a set of coefficients associated with a proper combination of Laguerre base functions. The resulting measures were compared with the traditional LF and HF power. A total of 236 ECG recordings were analyzed for validation, including autonomic outflow changes elicited by procedures of different nature and temporal variation, such as postural changes, lower body negative pressure, and handgrip tests. The proposed SAI-PAI measures consistently outperform traditional frequency-domain indexes in tracking expected instantaneous autonomic variations, both vagal and sympathetic, and may aid clinical decision making, showing reduced intersubject variability and physiologically plausible dynamics.

NEW & NOTEWORTHY While it is possible to obtain reliable estimates of parasympathetic activity from the ECG, a satisfying method to disentangle the sympathetic component from HRV has not been proposed yet. To overcome this long-lasting limitation, we propose two novel HRV-based indexes, the sympathetic and parasympathetic activity indexes.
Blunted shear-mediated dilation of the internal but not common carotid artery in response to lower body negative pressure
Authors: Iwamoto Erika , Bock Joshua M. , Casey Darren P.
Published: February 2018

Shear-mediated dilation in peripheral conduit arteries is blunted with sympathetic nervous system (SNS) activation; however, the effect of SNS activation on shear-mediated dilation in carotid arteries is unknown. We hypothesized that SNS activation reduces shear-mediated dilation in common and internal carotid arteries (CCA and ICA, respectively), and this attenuation is greater in the ICA compared with the CCA. Shear-mediated dilation in the CCA and ICA were measured in nine healthy men (24 ± 1 yr) with and without SNS activation. Shear-mediated dilation was induced by 3 min of hypercapnia (end‐tidal partial pressure of carbon dioxide +10 mmHg from individual baseline); SNS activity was increased with lower body negative pressure (LBNP; −20 mmHg). CCA and ICA measurements were made using Doppler ultrasound during hypercapnia with (LBNP) or without (Control) SNS activation. LBNP trials began with 5 min of LBNP with subjects breathing hypercapnic gas during the final 3 min. Shear-mediated dilation was calculated as the percent rise in peak diameter from baseline diameter. Sympathetic activation attenuated shear-mediated dilation in the ICA (Control vs. LBNP, 5.5 ± 0.7 vs. 1.8 ± 0.4%, P < 0.01), but not in the CCA (5.1 ± 1.2 vs. 4.2 ± 1.0%, P = 0.31). Moreover, absolute reduction in shear-mediated dilation via SNS activation was greater in the ICA than the CCA (−3.6 ± 0.7 vs. −0.9 ± 0.8%, P = 0.02). Our data indicate that shear-mediated dilation is attenuated during LBNP to a greater extent in the ICA compared with the CCA. These results potentially provide insight into the role of SNS activation on cerebral perfusion, as the ICA is a key supplier of blood to the brain.

NEW & NOTEWORTHY We explored the effect of acute sympathetic nervous system (SNS) activation on shear-mediated dilation in the common and internal carotid arteries (CCA and ICA, respectively) in young healthy men. Our data demonstrate that hypercapnia-induced vasodilation of the ICA is attenuated during lower body negative pressure to a greater extent than the CCA. These data may provide novel information related to the role of SNS activation on cerebral perfusion in humans.
Neurophysiological adaptations in the untrained side in conjunction with cross-education of muscle strength: a systematic review and meta-analysis
Authors: Manca Andrea , Hortobágyi Tibor , Rothwell John , Deriu Franca
Published: February 2018

We reviewed the evidence from randomized controlled trials (RCTs) focusing on the neurophysiological adaptations in the untrained side associated with cross-education of strength (CE) and pooled data into definite effect estimates for neurophysiological variables assessed in chronic CE studies. Furthermore, scoping directions for future research were provided to enhance the homogeneity and comparability of studies investigating the neural responses to CE. The magnitude of CE was 21.1 ± 18.2% (mean ± SD; P < 0.0001) in 22 RCTs ( n = 467 subjects) that measured at least 1 neurophysiological variable in the untrained side, including the following: electromyography (EMG; 14 studies); motor evoked potential (MEP; 8 studies); short-interval intracortical inhibition (SICI), recruitment curve, and M wave (6 studies); cortical silent period (cSP; 5 studies); interhemispheric inhibition, intracortical facilitation (ICF), and H reflex (2 studies); and V wave, short-interval ICF, short-latency afferent inhibition, and long-latency afferent inhibition (1 study). Only EMG, MEP, ICF, cSP, and SICI could be included in the meta-analysis (18 studies, n = 387). EMG ( P = 0.26, n = 235) and MEP amplitude ( P = 0.11, n = 145) did not change in the untrained limb after CE. cSP duration ( P = 0.02, n = 114) and SICI ( P = 0.001, n = 95) decreased in the untrained hemisphere according to body region and type and intensity of training. The magnitude of CE did not correlate with changes in these transcranial magnetic stimulation (TMS) measures. The design of this meta-analytical study and the lack of correlations prevented the ability to link mechanistically the observed neurophysiological changes to CE. Notwithstanding the limited amount of data available for pooling, the use of TMS to assess the ipsilateral neurophysiological responses to unilateral training still confirms the central neural origin hypothesis of chronic CE induced by strength training. However, how these neural adaptations contribute to CE remains unclear.
PKM2 Is Required to Activate Myeloid Dendritic Cells from Patients with Severe Aplastic Anemia
Authors: Liu Chunyan , Zheng Mengying , Wang Ting , Jiang Huijuan , Fu Rong , Wang Huaquan , Ding Kai , Zhou Qiufan , Shao Zonghong
Published: February 2018

Severe aplastic anemia (SAA) is an autoimmune disease in which bone marrow failure is mediated by activated myeloid dendritic cells (mDCs) and T lymphocytes. Recent research has identified a strong immunomodulatory effect of pyruvate kinase M2 (PKM2) on dendritic cells in immune‐mediated diseases. In this study, we aimed to explore the role of PKM2 in the activation of mDCs in SAA. We observed conspicuously higher levels of PKM2 in mDCs from SAA patients compared to normal controls at both the gene and protein levels. Concurrently, we unexpectedly discovered that after the mDC‐specific downregulation of PKM2, mDCs from patients with SAA exhibited weakened phagocytic activity and significantly decreased and shortened dendrites relative to their counterparts from normal controls. The expression levels of the costimulatory molecules CD86 and CD80 were also reduced on mDCs. Our results also suggested that PKM2 knockdown in mDCs reduced the abilities of these cells to promote the activation of CD8+ T cells (CTLs), leading to the decreased secretion of cytotoxic factors by the latter cell type. These findings demonstrate that mDC activation requires an elevated intrinsic PKM2 level and that PKM2 improves the immune status of patients with SAA by enhancing the functions of mDCs and, consequently, CTLs.
Levodopa-Responsive Early-Onset Parkinsonism in Down Syndrome
Authors: Palat Padmini , Hickey Francis , Patel Lina , Sannar Elise
Published: February 2018

Individuals with Down syndrome (DS) can develop Alzheimer’s disease as early as 30 to 40 years old, but parkinsonism is rarely described. We report on a 20-year-old woman with Down syndrome and parkinsonism who responded dramatically to carbidopa-levodopa. We propose that the occurrence of parkinsonism in individuals with DS may be underreported. Recognizing and treating this condition may improve quality of life.
Impact of SO2 on Alteration of Reservoir Rock with Ca-Deficient Conditions and Poor Buffering Capacity under a CO2 Geologic Storage Condition
Authors: Park Jinyoung , Choi Byoung-Young , Jeong Jong Ok , Shinn Young Jae
Published: February 2018

The objective of this study is to evaluate the impact of SO2-CO2-water-rock interaction on the alteration of a reservoir rock having Ca-deficient conditions and little buffering capacity and its implication for porosity change near the injection well from a CO2 storage pilot site, Republic of Korea. For our study, three cases of experimental and geochemical modeling were carried out (pure CO2, 0.1% SO2 in CO2, and 1% SO2 in CO2, resp.) under realistic geologic storage conditions. Our results show that SO2 accelerated water-rock interactions by lowering the pH. In the 1% SO2 case, pH remained less than 2 during the experiments because of insufficient buffering capacity. Sulfate minerals were not precipitated because of an insufficient supply of Ca. Because the total volume of precipitated secondary minerals was less than that of the dissolved primary minerals, the porosity of rock increased in all cases. Chlorite largely contributed to the decrease in total rock volume although it formed only 4.8 wt.% of the rock. Our study shows that the coinjection of a certain amount of SO2 at CO2 storage reservoirs without carbonate and Ca-rich minerals can significantly increase the porosity by enhancing water-rock interactions. This procedure can be beneficial to CO2 injection under some conditions.
Construction of Three‐Dimensional Road Surface and Application on Interaction between Vehicle and Road
Authors: Yongjie Lu , Wenqing Huai , Junning Zhang
Published: February 2018

The quantitative description is given to three‐dimensional micro and macro self‐similar characteristics of road surface from the perspective of fractal geometry using FBM stochastic midpoint displacement and diamond‐square algorithm in conjunction with fractal characteristics and statistical characteristics of standard pavement determined by estimation method of box‐counting dimension. The comparative analysis between reconstructed three‐dimensional road surface spectrum and theoretical road surface spectrum and correlation coefficient demonstrate the high reconstruction accuracy of fractal reconstructed road spectrum. Furthermore, the bump zone is taken as an example to reconstruct a more arbitrary 3D road model through isomorphism of special road surface with stochastic road surface model. Measurement is taken to assume the tire footprint on road surface to be a rectangle, where the pressure distribution is expressed with mean stiffness, while the contact points in the contact area are replaced with a number of springs. Two‐DOF vehicle is used as an example to analyze the difference between three‐dimensional multipoint‐and‐plane contact and traditional point contact model. Three‐dimensional road surface spectrum provides a more accurate description of the impact effect of tire on road surface, thereby laying a theoretical basis for studies on the dynamical process of interaction of vehicle‐road surface and the road friendliness.
A Family of Measures of Noncompactness in the Locally Sobolev Spaces and Its Applications to Some Nonlinear Volterra Integrodifferential Equations
Authors: Mehravaran H. , Khanehgir M. , Allahyari R.
Published: February 2018

We study a new family of measures of noncompactness in the locally Sobolev space Wlocn,1(R+N), equipped with a suitable topology. As an application of the technique associated with this family of measures of noncompactness, we study the existence of solutions for a class of nonlinear Volterra integrodifferential equations. Further, we give an illustrative example to verify the effectiveness and applicability of our results.
Factors Related to a Right-Left Difference in Visual Field Defect in the Eyes with Untreated Normal Tension Glaucoma
Authors: Moroi Haruka , Anraku Ayako , Ishida Kyoko , Tomita Goji
Published: February 2018

Purpose. To investigate factors related to a right-left difference in visual field defect in untreated normal tension glaucoma (NTG). Methods. The medical records of 92 patients with untreated NTG were reviewed. Ocular blood flow was evaluated with laser speckle flowgraphy, and the mean blur rate (MBR) at the optic nerve head was analyzed. Relationships between right-left differences in mean deviation (MD), intraocular pressure, MBR, spherical equivalent, central corneal thickness, and mean ocular perfusion pressure were evaluated using Spearman’s rank correlation coefficient. Multiple regression analysis was used to detect factors contributing to a right-left difference in MD. Results. The right-left difference in MD was correlated with differences in intraocular pressure (r=−0.263, P=0.011), MBR (r=0.417, P<0.001), and spherical equivalent (r=0.213, P=0.042), but not with central corneal thickness or mean ocular perfusion pressure. Multiple regression analysis showed that a difference in MBR was the only significant contributor to a right-left difference in MD (slope 0.047, 95% confidence interval 0.025–0.069; P<0.001). Conclusion. In untreated NTG, a difference in blood flow at the optic nerve head was a significant contributor to a right-left difference in visual field defect.
Diagnosis of Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery with Echocardiography and Digital Subtraction Angiography
Authors: Yang Haiyan , Li Jinqing , Ji Xiaojuan
Published: February 2018

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a common coronary artery anomaly associated with high mortality and may lead to sudden death if left unrecognized and untreated. This report describes an 8-year-old female who had cardiac murmur but with no clinical symptoms. Electrocardiogram (ECG) was normal, but echocardiography made the diagnosis of ALCAPA. Digital subtraction angiography (DSA) with cardiac catheterization angiography (CAG) confirmed the diagnosis, and finally, the patient received surgery. This case demonstrates that echocardiography is a sensitive and convenient technique for establishing the initial diagnosis of ALCAPA in both symptomatic and asymptomatic patients.
A Robust Fiber Bragg Grating Hydrogen Gas Sensor Using Platinum-Supported Silica Catalyst Film
Authors: Kurohiji Marina , Ichiriyama Seiji , Yamasaku Naoki , Okazaki Shinji , Kasai Naoya , Maru Yusuke , Mizutani Tadahito
Published: February 2018

A robust fiber Bragg grating (FBG) hydrogen gas sensor for reliable multipoint-leakage monitoring has been developed. The sensing mechanism is based on shifts of center wavelength of the reflection spectra due to temperature change caused by catalytic combustion heat. The sensitive film which consists of platinum-supported silica (Pt/SiO2) catalyst film was obtained using sol-gel method. The precursor solution was composed of hexachloroplatinic acid and commercially available silica precursor solution. The atom ratio of Si : Pt was fixed at 13 : 1. A small amount of this solution was dropped on the substrate and dried at room temperature. After that, the film was calcined at 500°C in air. These procedures were repeated and therefore thick hydrogen-sensitive films were obtained. The catalytic film obtained by 20-time coating on quartz glass substrate showed a temperature change 75 K upon exposure to 3 vol.% H2. For realizing robust sensor device, this catalytic film was deposited and FBG portion was directly fixed on titanium substrate. The sensor device showed good performances enough to detect hydrogen gas in the concentration range below lower explosion limit at room temperature. The enhancement of the sensitivity was attributed to not only catalytic combustion heat but also related thermal strain.
A Novel Mutation in TSC2 Gene: A 34-Year-Old Female with Pulmonary Lymphangioleiomyomatosis with Concomitant Hepatic Lesions
Authors: Nadiri Mehdi , Raeisi Mortaza , Mousavi Aghdas Seyed Ali
Published: February 2018

Tuberous sclerosis complex (TSC) is an autosomal dominant disease resulting from mutation(s) in TSC1 or TSC2 genes. TSC is associated with the formation of hamartomas in the brain, heart, eyes, skin, kidneys, and lymphangioleiomyomatosis (LAM) of the lungs. LAM is almost restricted to women in reproductive age. Different mutations in TSC1 and TSC2 genes have been reported in the literature. Here, we present a female patient with TSC-LAM with a novel mutation in TSC2 gene. The patient also had multiple hepatic angiomyolipomas, which is a relatively less-reported manifestation of the disease. The impact of this mutation on the pattern of disease presentation and response to treatment is not clear yet.
Type Synthesis of 5-DoF Parallel Mechanisms with Different Submechanisms
Authors: Lu Yi , Lu Yang , Zhang Lijie , Ye Nijia , Hu Bo , Liu Yang
Published: February 2018

The type synthesis of the 5-DoF (degree of freedom) parallel mechanisms with different submechanisms is studied by utilizing digital topology graphs (DTGs). The conditions for synthesizing the 5-DoF parallel mechanisms with different submechanisms using DTGs are determined. Many valid DTGs are derived from 17 different 5-DoF associated linkages, and the valid DTGs are transformed into revised DTGs. The subplanar and/or spatial parallel mechanisms in the 5-DoF parallel mechanisms are transformed into some simple equivalent limbs, and their equivalent relations and merits are analyzed. Using the derived valid DTGs and revised DTGs, many 5-DoF parallel mechanisms with different subserial or parallel mechanisms are synthesized, and they are simplified by replacing the complicated subparallel mechanisms with their simple equivalent limbs. Finally, their DoFs are calculated to verify the correctness and effectiveness of the proposed approach.
The Effects of Aloe vera Cream on the Expression of CD4+ and CD8+ Lymphocytes in Skin Wound Healing
Authors: Prakoso Yos Adi , Kurniasih
Published: February 2018

The aim of this study is to explore the effect of topical application of Aloe vera on skin wound healing. Thirty-six male Sprague-Dawley rats weighing 150–200 grams were divided into four groups. All groups were anesthetized, shaved, and exposed to round full-thickness punch biopsy on the back: group I (control); group II (treated with 1% Aloe vera cream); group III (treated with 2% Aloe vera cream); and group IV (treated with madecassol®). The treatments were given once a day. Macroscopic and microscopic examination were observed at 5, 10, and 15 days after skin biopsy. Skin specimens were prepared for histopathological study using H&E stain and IHC stain against CD4+ and CD8+ lymphocytes. All the data were analyzed using SPSS16. The result showed that topical application of 1% and 2% Aloe vera cream significantly reduced the percentage of the wound, leucocytes infiltration, angiogenesis, and expression of CD8+ lymphocytes and increased the epidermal thickness and the expression of CD4+ lymphocytes (p ≤ 0,05). There was no significant difference in the number of fibroblasts in all groups. Topical application of 1% and 2% Aloe vera cream has wound healing potential via their ability to increase the ratio of CD4+/CD8+ lymphocytes in the wound area.
The Response of Duckweed (Lemna minor L.) Roots to Cd and Its Chemical Forms
Authors: Xue Yan , Wang Jin-qin , Huang Jin , Li Feng-ying , Wang Ming
Published: February 2018

The response of duckweed (Lemna minor L.) roots to Cd and its chemical forms was investigated. The relative root growth rate and concentrations of Cd and its different chemical forms in the root, that is, ethanol-extractable (FE-Cd), HCl-extractable (FHCl-Cd), and residual fractions (Fr-Cd), were quantified. Weibull model was used to unravel the regression between the relative root elongation (RRL) with chemical forms of Cd. Parameters assessed catalase (CAT), peroxidases (POD), and superoxide dismutase (SOD), as well as malondialdehyde (MDA) and total antioxidant capacity (A-TOC). Our results show that both the relative root growth rate and relative frond number were affected by Cd concentrations. The chemical forms of Cd were influenced by Cd content in the medium. Relative root elongation (RRL) showed a significant correlation with chemical forms of Cd. Additionally, POD and SOD increased at lower Cd concentrations followed by a decrease at higher Cd concentrations (at more than 5 μM Cd). Moreover, MDA and A-TOC increased and CAT decreased with increasing Cd exposure. Furthermore, CAT showed a significant correlation with FHCl-Cd. Taken together, it can be concluded that the chemical forms of Cd are statistically significant predictors of Cd toxicity to duckweed and to the other similar aquatic plants.
Effects of Alloying Elements (Cr, Mn) on Corrosion Properties of the High‐Strength Steel in 3.5% NaCl Solution
Authors: Kim Bomi , Kim Soojin , Kim Heesan
Published: February 2018

Effects of chromium and manganese as alloying elements on corrosion resistance of carbon steel were examined using evaluation of corrosion resistance in 60°C NaCl solution with a weight loss test, polarization test, analysis of rust with X‐ray diffractometer, Raman spectroscopy, transmission electron microscopy, energy dispersive spectroscopy, and electron energy loss spectroscopy. The weight loss behavior conformed to a typical parabolic law, and the oxidation state of iron in rust was higher along the fast pathway but was disproportionate to the distance from the alloy/AR interface. It suggests that the corrosion process of the alloys was controlled by transport of oxygen to the rust layer. The improvements in corrosion resistance of 18Mn and 18Mn5Cr resulted from both the refinement of grain in adherent rust (AR) and the increase of the amounts of goethite in nonadherent rust (NAR) by chromium and manganese. Especially, the effectiveness of chromium on corrosion resistance was also related to the refinements of grain in AR and the amounts of goethite in NAR. The Tafel extrapolation method was inadequate to measure the instantaneous corrosion rate of steels with various alloying elements and immersion periods because of the difference in electrochemical reduction rates of rust, depending on its constituent.
Unusual Life-Threatening Pneumothorax Complicating a Ruptured Complex Aspergilloma in an Immunocompetent Patient in Cameroon
Authors: Nonga Bernadette Ngo , Jemea Bonaventure , Pondy Angele O. , Handy Eone Daniel , Bitchong Marie Claire , Fola Olivier , Nkolaka Atems , Londji Gilles Martin
Published: February 2018

An aspergilloma is a well-recognized lesion of the lung caused most of the time by the fungus Aspergillus fumigatus. Its main complication is hemoptysis and has been very rarely associated with tension pneumothorax. We present the case of a 47-year-old man with a history of treated and healed tuberculosis, which was successfully managed in our service for a ruptured right upper lobe complexed aspergilloma, complicated by a massive and tension pneumothorax. The patient underwent thoracotomy and lung resection with quick recovery. Conclusively, although rare, an aspergilloma may rupture and cause a life-threatening air leakage.
A Challenging Case of Severe Ulcerative Colitis following the Initiation of Secukinumab for Ankylosing Spondylitis
Authors: Ehrlich Dean , Jamaluddin Nimah , Pisegna Joseph , Padua David
Published: February 2018

Secukinumab is an interleukin-17 inhibitor used for the treatment of ankylosing spondylitis (AS), psoriasis, and psoriatic arthritis. The risk of exacerbating underlying inflammatory bowel disease (IBD) in patients being treated with secukinumab for other conditions is controversial. We document a patient with AS and previously undiagnosed IBD, found to be in a severe ulcerative colitis flare shortly after receiving the loading dose of secukinumab. There are no guidelines regarding biologic salvage therapy for IBD in the setting of active treatment with another biologic agent. After waiting one half-life of secukinumab, our patient had an excellent response to initiation of infliximab.
Single-Cell Transcriptome Analyses Reveal Endothelial Cell Heterogeneity in Tumors and Changes following Antiangiogenic Treatment
Authors: Zhao Qi , Eichten Alexandra , Parveen Asma , Adler Christina , Huang Ying , Wang Wei , Ding Yueming , Adler Alexander , Nevins Thomas , Ni Min , Wei Yi , Thurston Gavin
Published: February 2018

Angiogenesis involves dynamic interactions between specialized endothelial tip and stalk cells that are believed to be regulated in part by VEGF and Dll4-Notch signaling. However, our understanding of this process is hampered by limited knowledge of the heterogeneity of endothelial cells and the role of different signaling pathways in specifying endothelial phenotypes. Here, we characterized by single-cell transcriptomics the heterogeneity of mouse endothelial cells and other stromal cells during active angiogenesis in xenograft tumors as well as from adult normal heart, following pharmacologic inhibition of VEGF and Dll4-Notch signaling. We classified tumor endothelial cells into three subpopulations that appeared to correspond with tip-like, transition, and stalk-like cells. Previously identified markers for tip and stalk cells were confirmed and several novel ones discovered. Blockade of VEGF rapidly inhibited cell-cycle genes and strongly reduced the proportion of endothelial tip cells in tumors. In contrast, blockade of Dll4 promoted endothelial proliferation as well as tip cell markers; blockade of both pathways inhibited endothelial proliferation but preserved some tip cells. We also phenotypically classified other tumor stromal cells and found that tumor-associated fibroblasts responded to antiangiogenic drug treatments by upregulating hypoxia-associated genes and producing secreted factors involved in angiogenesis. Overall, our findings better define the heterogeneity of tumor endothelial and other stromal cells and reveal the roles of VEGF and Dll4-Notch in specifying tumor endothelial phenotype, highlighting the response of stromal cells to antiangiogenic therapies.

Significance: These findings provide a framework for defining subpopulations of endothelial cells and tumor-associated fibroblasts and their rapid changes in gene expression following antiangiogenic treatment. Cancer Res; 78(9); 2370–82. ©2018 AACR.
Abstract ES10-3: Breast cancer patient-derived xenografts as models for metastatic progression and therapeutic response
Authors: Welm AL
Published: February 2018

Metastasis is the main cause of death from breast cancer, and yet little is understood with regard to how to prevent tumors from appearing in distant organs as metastases, or how to treat them once they appear. Using new models and approaches, we have discovered a new pathway regulating metastasis to lungs and bones. We found that RON kinase regulates breast cancer metastasis through cell-autonomous and non-cell-autonomous mechanisms. This presentation will cover use of various models of breast cancer to study metastasis and therapy response, including patient-derived xenograft (PDX) models. PDX models represent the diversity of human breast tumors, and can be feasibly utilized to test new drugs and drug combinations to find therapeutic approaches that match with molecular features of various tumor types. The goal of our work is to utilize PDX and other relevant in vivo models to obtain preclinical data that will facilitate prioritization of drugs to be tested in breast cancer clinical trials, including RON kinase inhibitors. Taken together, these elements converge to reveal high-priority treatment strategies for future clinical trials in breast cancer patients.

Citation Format: Welm AL. Breast cancer patient-derived xenografts as models for metastatic progression and therapeutic response [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES10-3.
Abstract ES2-1: The pathology of high risk proliferative lesions of the breast
Authors: Siziopikou KP
Published: February 2018

A number of breast lesions diagnosed by pathologic examination of breast tissue are known to confer an increased risk for future development of breast cancer. Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) are lesions conferring a moderately increased risk of 4-5x over baseline. Lobular carcinoma in situ (LCIS) and variants confer a markedly increased risk of 8-10x over the baseline. The magnitude of the risk, the effect of the patient's age and family history, the laterality of the future malignancy and the type of subsequent cancer development are different between all these high risk proliferative breast lesions. In addition, the spectrum of columnar cell lesions of the breast are thought to represent an early non-obligate precursor in the development of the low grade neoplasia of the breast. Of interest, many of these lesions share common genetic abnormalities that are different than those seen in high grade in situ and invasive carcinomas of the breast. These observations have implications for our current understanding of the breast cancer progression model and our recommendations for the therapeutic management of patients with high risk proliferative lesions of the breast.

Citation Format: Siziopikou KP. The pathology of high risk proliferative lesions of the breast [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES2-1.
Abstract GS5-01: Appropriate margins for breast conserving surgery in patients with early stage breast cancer: A meta-analysis
Authors: Shah C , Verma V , Sayles H , Recht A , Vicini F
Published: February 2018

Background: Significant controversy exists regarding the appropriate minimum tumor-free margin width for patients undergoing breast-conserving therapy. The SSO-ASTRO guidelines recommend 'no ink on tumor' based upon a meta-analysis of 33 studies, but this had significant limitations. In order to address these concerns, a meta-analysis of all available data (using 31 of the initial studies) was performed but employing stricter criteria for acceptability and quality of evaluable studies.

Methods: Study eligibility criteria were: (1) minimum follow-up of 50 months; (2) explicit pathologic criteria for defining margins; and (3) consistent endpoints associated with local recurrence. The compiled studies were analyzed using generalized linear mixed models for the outcome of local recurrence, with random effects for study and fixed effects for various patient and study characteristics.

Results: The analysis incorporated 38 studies, which included 55,302 patients treated from 1968-2010. Two of the previous studies were excluded (one because of short follow-up, and the second because it was updated) with seven new studies added from the previous meta-analysis including an update of a previously included analysis. Median follow-up was 7.2 years. The median age of the cohort was 55 years, 74% of patients had T1 tumors, and 72% were node negative. The crude rate of local recurrence for patients with positive margins was 10.3%, compared to 3.8% for those with negative margins defined as no tumor on ink or wider (p<0.001). The crude rates of local recurrence decreased as the margin distance increased: 7.2% for patients with margins >0-<2 mm, 3.6% for margins of 2-5 mm (3.6%), and 3.2% for margins wider than 5 mm (p<0.001 for each). Use of endocrine therapy and increasing median study year were associated with a reduction in local recurrence in univariate models but not in multivariable analyses.

Conclusions: The current meta-analysis indicates that having margin widths 2 mm or greater is associated with a lower risk of ipsilateral breast failure than narrower but uninvolved margins. It therefore fails to confirm that 'no-tumor on ink' is optimal. Further analyses are needed to clarify this issue, particularly to identify the critical minimum tumor-free margin for different patient subgroups.

Citation Format: Shah C, Verma V, Sayles H, Recht A, Vicini F. Appropriate margins for breast conserving surgery in patients with early stage breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS5-01.
Abstract MS1-1: Targeting DNA repair deficiency in triple negative breast cancers (TNBC) with G-quadruplex stabilisers
Authors: Aparicio S
Published: February 2018

Triple negative breast cancers (TNBC) represent a heterogeneous group of patients where pathway targeted interventions are lacking. We have recently identified new subgroups of TNBC tumours based on patterns of genomic instability, suggesting that deficiencies in DNA repair or genome maintenance could be exploited in specific subgroups of TNBC patients. We recently discovered synthetic lethal activity for small molecules that bind and stabilise G-quadruplex (G4) structures in the human genome. Stabilized G4 structures are considered "at risk" during DNA replication, leading to single strand and double strand breaks in the absence of DNA repair. This has specific application in cancers with DNA repair deficiency. We have shown that loss of homologous recombination repair capacity in breast cancers is associated with ∼ 1 log order increase in sensitivity to G4 binders. Moreover this activity has been observed in platinum pre-treated tumours, and in PARP insensitive tumours. Recently through CRISPR screening approaches we have defined additional DNA repair lesions that confer synthetic lethality to G4 binders. This mechanism of G4 stabilisation is now being tested in a phase 1/2 clinical trial of CX5461 in breast cancer patients.

Citation Format: Aparicio S. Targeting DNA repair deficiency in triple negative breast cancers (TNBC) with G-quadruplex stabilisers [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr MS1-1.
Abstract MS1-2: New clinical approaches for TNBC
Authors: Telli M
Published: February 2018

Over the last decade, triple-negative breast cancer (TNBC) has been the subject of intense clinical investigation. Importantly, an improved understanding of the critical role of DNA damage repair deficiency in TNBC has led to effective therapeutic strategies to target BRCA1 and BRCA2 mutation-associated TNBCs with platinum chemotherapy agents and PARP inhibitors. A major area of increasing clinical relevance focuses on the treatment of BRCA1 and BRCA2 mutation-associated breast cancers after the development of resistance to platinum and PARP inhibitor therapy. Lurbinectedin, a novel marine derived DNA damaging agent, has shown activity in BRCA1 and BRCA2 mutation-associated cancers, including those with platinum resistance.

While therapeutic strategies for TNBC patients with BRCA1 and BRCA2 mutations have increased, most TNBC patients lack an underlying germline mutation in these genes and continue to have high unmet clinical need. Multiple lines of investigation are currently underway. Androgen receptor (AR) blockade has shown preliminary proof-of-concept in AR expressing TNBCs. While monotherapy with PD-1/PD-L1 checkpoint inhibitors has shown modest activity in metastatic TNBC, multiple studies are exploring the role of these agents in combination with chemotherapy, targeted therapies and other immunotherapeutic agents. Given the high prevalence of TP53 mutations in TNBC, strategies to target additional cell cycle checkpoints including ATR, ATM, Wee1 and others may hold promise. Antibody-drug conjugates targeting Trop-2, LIV-1 and GPNMB expressing TNBCs have also shown clinical activity and are advancing in clinical development.

Citation Format: Telli M. New clinical approaches for TNBC [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr MS1-2.