bluuebunny/crossref_metadata_2025 huggingface dataset:
China and the South China Sea “Lawfare”
Authors: HSIAO ANNE HSIU-AN
Published: December 2016

The strategic values of the South China Sea had long been recognized. More recently, the South China Sea has once again become an international flashpoint, as disputes take place in the context of a rising and perceived more assertive People’s Republic of China (China) vis-à-vis a relatively declining US that seeks to retain its influence and interests in East Asia. This paper tries to illustrate the growing strategic role of international law in the geopolitics of the South China Sea at play — a subject matter that has so far been less explored — and to assess how the intensified legal maneuvers, or “lawfare” between China on the one hand, and other South China Sea claimants as well as the US on the other, reflect China’s attitude toward the South China Sea dispute and may impact upon the peace and security in the region. It concludes that the “lawfare” since 2009, especially the South China Sea arbitration proceedings initiated by the Philippines, may have not only increased the uncertainties of China’s behavior and China–US relations, but also made the situations in both East and South China seas more complicated. Moreover, China’s responses in the “lawfare” also suggest that China has become more “rule-of-law oriented” as well as hegemonic. The dual images of China raise some uncertainty as to how the South China Sea disputes might eventually be resolved.
Dielectric properties of benzylamine in 1,2,6-hexanetriol mixture using time domain reflectometry technique
Authors: Swami M. B. , Hudge P. G. , Pawar V. P.
Published: December 2016

The dielectric properties of binary mixtures of benzylamine-1,2,6-hexantriol mixtures at different volume fractions of 1,2,6-hexanetriol have been measured using Time Domain Reflectometry (TDR) technique in the frequency range of 10 MHz to 30 GHz. Complex permittivity spectra were fitted using Havriliak–Negami equation. By using least square fit method the dielectric parameters such as static dielectric constant ([Formula: see text]), dielectric constant at high frequency ([Formula: see text]), relaxation time [Formula: see text] (ps) and relaxation distribution parameter ([Formula: see text]) were extracted from complex permittivity spectra at 25[Formula: see text]C. The intramolecular interaction of different molecules has been discussed using the Kirkwood correlation factor, Bruggeman factor. The Kirkwood correlation factor ([Formula: see text]) and effective Kirkwood correlation factor ([Formula: see text]) indicate the dipole ordering of the binary mixtures.
The influence of volcanic rocks on the characterization of Rosebank Field – new insights from ocean-bottom seismic data and geological analogues integrated through interpretation and modelling
Authors: Poppitt S. , Duncan L. J. , Preu B. , Fazzari F. , Archer J.
Published: December 2016

During Late Paleocene–Early Eocene times, the modern Rosebank structure was located at the juxtaposition of the easterly advancing Flett volcanic system and the northerly prograding Flett delta. As a result, the Rosebank reservoir sandstones are interstratified with volcanic and volcaniclastic rocks, offering challenges for reservoir imaging, depth prediction and reservoir characterization. These challenges have driven the application of Ocean Bottom Node (OBN) seismic technology. OBN data have yielded improved velocity models for depth conversion, better reservoir definition and key insights to aid the modelling of sand distribution from seismic attributes. Spectral decomposition of the OBN seismic data has facilitated the extraction of distinct volcanic subunits, whilst spectral enhancement has enabled visualization of complex stacking patterns within individual igneous layers. To complement the seismic analysis, detailed geological analogue studies have been undertaken in volcanic provinces such as the Palaeogene volcanic district of SE Greenland and the Columbia River Flood Basalt Province, USA. No single outcrop provides a definitive analogy to Rosebank, but each offers insights that provide an important link to understanding and managing the main subsurface uncertainties associated with field development. Integration of these multiple workflows have improved the reservoir characterization and provided the foundation for the optimization of the field development plan.
Don't replace people. Augment them.
Authors: O'Reilly Tim
Published: December 2016

If we let machines put us out of work, it will be because of a failure of imagination and the will to make a better future!
Hybrid workplaces of the future
Authors: Kamar Ece
Published: December 2016

Are you ready to meet your new teammates?
The gig economy
Authors: Parigi Paolo , Ma Xiao
Published: December 2016

Gig jobs have become a structural aspect of contemporary economic landscape, creating unique social and technological challenges. How can policies and design solutions better protect gig workers and mitigate the risks participants face?
Algorithmic bosses, robotic colleagues: toward human-centered algorithmic workplaces
Authors: Lee Min Kyung
Published: December 2016

We already know algorithms can make our lives and our work more efficient, but how can we go beyond that to create trustworthy, fair, and enjoyable workplaces in which workers can find meaning and continuously learn?
The hidden faces of automation
Authors: Irani Lilly
Published: December 2016

As we dream of automation, we always need people to calibrate and train what we automate. Automation has hidden human faces.
The future of microwork
Authors: Teevan Jaime
Published: December 2016

What happens when we algorithmically break complex productivity tasks down into microtasks? At Microsoft Research, the author and her team are accelerating a shift toward microproductivity to make it easy for people to get big things done one small step at a time.
Critical role of microbiota within cecal crypts on the regenerative capacity of the intestinal epithelium following surgical stress
Authors: Zaborin Alexander , Krezalek Monika , Hyoju Sanjiv , Defazio Jennifer R. , Setia Namrata , Belogortseva Natalia , Bindokas Vytautas P. , Guo Qiti , Zaborina Olga , Alverdy John C.
Published: December 2016

Cecal crypts represent a unique niche that are normally occupied by the commensal microbiota. Due to their density and close proximity to stem cells, microbiota within cecal crypts may modulate epithelial regeneration. Here we demonstrate that surgical stress, a process that invariably involves a short period of starvation, antibiotic exposure, and tissue injury, results in cecal crypt evacuation of their microbiota. Crypts devoid of their microbiota display pathophysiological features characterized by abnormal stem cell activation as judged by leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) staining, expansion of the proliferative zone toward the tips of the crypts, and an increase in apoptosis. In addition, crypts devoid of their microbiota display loss of their regenerative capacity as assessed by their ability to form organoids ex vivo. When a four-member human pathogen community isolated from the stool of a critically ill patient is introduced into the cecum of mice with empty crypts, crypts become occupied by the pathogens and further disruption of crypt homeostasis is observed. Fecal microbiota transplantation restores the cecal crypts’ microbiota, normalizes homeostasis within crypts, and reestablishes crypt regenerative capacity. Taken together, these findings define an emerging role for the microbiota within cecal crypts to maintain epithelial cell homeostasis in a manner that may enhance recovery in response to the physiological stress imposed by the process of surgery.

NEW & NOTEWORTHY This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts.
Kvβ1.1 (AKR6A8) senses pyridine nucleotide changes in the mouse heart and modulates cardiac electrical activity
Authors: Tur Jared , Chapalamadugu Kalyan C. , Katnik Christopher , Cuevas Javier , Bhatnagar Aruni , Tipparaju Srinivas M.
Published: December 2016

The present study investigates the physiological role of Kvβ1 subunit for sensing pyridine nucleotide (NADH/NAD+) changes in the heart. We used Kvβ1.1 knockout (KO) or wild-type (WT) mice and established that Kvβ1.1 preferentially binds with Kv4.2 and senses the pyridine nucleotide changes in the heart. The cellular action potential duration (APD) obtained from WT cardiomyocytes showed longer APDs with lactate perfusion, which increases intracellular NADH levels, while the APDs remained unaltered in the Kvβ1.1 KO. Ex vivo monophasic action potentials showed a similar response, in which the APDs were prolonged in WT mouse hearts with lactate perfusion; however, the Kvβ1.1 KO mouse hearts did not show APD changes upon lactate perfusion. COS-7 cells coexpressing Kv4.2 and Kvβ1.1 were used for whole cell patch-clamp recordings to evaluate changes caused by NADH (lactate). These data reveal that Kvβ1.1 is required in the mediated inactivation of Kv4.2 currents, when NADH (lactate) levels are increased. In vivo, isoproterenol infusion led to increased NADH in the heart along with QTc prolongation in wild-type mice; regardless of the approach, our data show that Kvβ1.1 recognizes NADH changes and modulates Kv4.2 currents affecting AP and QTc durations. Overall, this study uses multiple levels of investigation, including the heterologous overexpression system, cardiomyocyte, ex vivo, and ECG, and clearly depicts that Kvβ1.1 is an obligatory sensor of NADH/NAD changes in vivo, with a physiological role in the heart.

NEW & NOTEWORTHY Cardiac electrical activity is mediated by ion channels, and Kv4.2 plays a significant role, along with its binding partner, the Kvβ1.1 subunit. In the present study, we identify Kvβ1.1 as a sensor of pyridine nucleotide changes and as a modulator of Kv4.2 gating, action potential duration, and ECG in the mouse heart.
Differential effects of Mas receptor deficiency on cardiac function and blood pressure in obese male and female mice
Authors: Wang Yu , Shoemaker Robin , Powell David , Su Wen , Thatcher Sean , Cassis Lisa
Published: December 2016

Angiotensin-(1–7) [ANG-(1–7)] acts at Mas receptors (MasR) to oppose effects of angiotensin II (ANG II). Previous studies demonstrated that protection of female mice from obesity-induced hypertension was associated with increased systemic ANG-(1–7), whereas male obese hypertensive mice exhibited increased systemic ANG II. We hypothesized that MasR deficiency ( MasR−/−) augments obesity-induced hypertension in males and abolishes protection of females. Male and female wild-type ( MasR+/+) and MasR−/− mice were fed a low-fat (LF) or high-fat (HF) diet for 16 wk. MasR deficiency had no effect on obesity. At baseline, male and female MasR−/− mice had reduced ejection fraction (EF) and fractional shortening than MasR+/+ mice. Male, but not female, HF-fed MasR+/+ mice had increased systolic and diastolic (DBP) blood pressures compared with LF-fed controls. In HF-fed females, MasR deficiency increased DBP compared with LF-fed controls. In contrast, male HF-fed MasR−/− mice had lower DBP than MasR+/+ mice. We quantified cardiac function after 1 mo of HF feeding in males of each genotype. HF-fed MasR−/− mice had higher left ventricular (LV) wall thickness than MasR+/+ mice. Moreover, MasR+/+, but not MasR−/−, mice displayed reductions in EF from HF feeding that were reversed by ANG-(1–7) infusion. LV fibrosis was reduced in HF-fed MasR+/+ but not MasR−/− ANG-(1–7)-infused mice. These results demonstrate that MasR deficiency promotes obesity-induced hypertension in females. In males, HF feeding reduced cardiac function, which was restored by ANG-(1–7) in MasR+/+ but not MasR−/− mice. MasR agonists may be effective therapies for obesity-associated cardiovascular conditions.

NEW & NOTEWORTHY MasR deficiency abolishes protection of female mice from obesity-induced hypertension. Male MasR-deficient obese mice have reduced blood pressure and declines in cardiac function. ANG-(1–7) infusion restores obesity-induced cardiac dysfunction of wild-type, but not MasR-deficient, male mice. MasR agonists may be cardioprotective in obese males and females.
Endothelial cell signaling and ventilator-induced lung injury: molecular mechanisms, genomic analyses, and therapeutic targets
Authors: Wang Ting , Gross Christine , Desai Ankit A. , Zemskov Evgeny , Wu Xiaomin , Garcia Alexander N. , Jacobson Jeffrey R. , Yuan Jason X.-J. , Garcia Joe G. N. , Black Stephen M.
Published: December 2016

Mechanical ventilation is a life-saving intervention in critically ill patients with respiratory failure due to acute respiratory distress syndrome (ARDS). Paradoxically, mechanical ventilation also creates excessive mechanical stress that directly augments lung injury, a syndrome known as ventilator-induced lung injury (VILI). The pathobiology of VILI and ARDS shares many inflammatory features including increases in lung vascular permeability due to loss of endothelial cell barrier integrity resulting in alveolar flooding. While there have been advances in the understanding of certain elements of VILI and ARDS pathobiology, such as defining the importance of lung inflammatory leukocyte infiltration and highly induced cytokine expression, a deep understanding of the initiating and regulatory pathways involved in these inflammatory responses remains poorly understood. Prevailing evidence indicates that loss of endothelial barrier function plays a primary role in the development of VILI and ARDS. Thus this review will focus on the latest knowledge related to 1) the key role of the endothelium in the pathogenesis of VILI; 2) the transcription factors that relay the effects of excessive mechanical stress in the endothelium; 3) the mechanical stress-induced posttranslational modifications that influence key signaling pathways involved in VILI responses in the endothelium; 4) the genetic and epigenetic regulation of key target genes in the endothelium that are involved in VILI responses; and 5) the need for novel therapeutic strategies for VILI that can preserve endothelial barrier function.
Capsaicin-induced Ca2+signaling is enhanced via upregulated TRPV1 channels in pulmonary artery smooth muscle cells from patients with idiopathic PAH
Authors: Song Shanshan , Ayon Ramon J. , Yamamura Aya , Yamamura Hisao , Dash Swetaleena , Babicheva Aleksandra , Tang Haiyang , Sun Xutong , Cordery Arlette G. , Khalpey Zain , Black Stephen M. , Desai Ankit A. , Rischard Franz , McDermott Kimberly M. , Garcia Joe G. N. , Makino Ayako , Yuan Jason X.-J.
Published: December 2016

Capsaicin is an active component of chili pepper and a pain relief drug. Capsaicin can activate transient receptor potential vanilloid 1 (TRPV1) channels to increase cytosolic Ca2+concentration ([Ca2+]cyt). A rise in [Ca2+]cytin pulmonary artery smooth muscle cells (PASMCs) is an important stimulus for pulmonary vasoconstriction and vascular remodeling. In this study, we observed that a capsaicin-induced increase in [Ca2+]cytwas significantly enhanced in PASMCs from patients with idiopathic pulmonary arterial hypertension (IPAH) compared with normal PASMCs from healthy donors. In addition, the protein expression level of TRPV1 in IPAH PASMCs was greater than in normal PASMCs. Increasing the temperature from 23 to 43°C, or decreasing the extracellular pH value from 7.4 to 5.9 enhanced capsaicin-induced increases in [Ca2+]cyt; the acidity (pH 5.9)- and heat (43°C)-mediated enhancement of capsaicin-induced [Ca2+]cytincreases were greater in IPAH PASMCs than in normal PASMCs. Decreasing the extracellular osmotic pressure from 310 to 200 mOsmol/l also increased [Ca2+]cyt, and the hypo-osmolarity-induced rise in [Ca2+]cytwas greater in IPAH PASMCs than in healthy PASMCs. Inhibition of TRPV1 (with 5′-IRTX or capsazepine) or knockdown of TRPV1 (with short hairpin RNA) attenuated capsaicin-, acidity-, and osmotic stretch-mediated [Ca2+]cytincreases in IPAH PASMCs. Capsaicin induced phosphorylation of CREB by raising [Ca2+]cyt, and capsaicin-induced CREB phosphorylation were significantly enhanced in IPAH PASMCs compared with normal PASMCs. Pharmacological inhibition and knockdown of TRPV1 attenuated IPAH PASMC proliferation. Taken together, the capsaicin-mediated [Ca2+]cytincrease due to upregulated TRPV1 may be a critical pathogenic mechanism that contributes to augmented Ca2+influx and excessive PASMC proliferation in patients with IPAH.
Alternative hematological and vascular adaptive responses to high-altitude hypoxia in East African highlanders
Authors: Cheong Hoi I. , Janocha Allison J. , Monocello Lawrence T. , Garchar Adrianna C. , Gebremedhin Amha , Erzurum Serpil C. , Beall Cynthia M.
Published: December 2016

Elevation of hemoglobin concentration, a common adaptive response to high-altitude hypoxia, occurs among Oromo but is dampened among Amhara highlanders of East Africa. We hypothesized that Amhara highlanders offset their smaller hemoglobin response with a vascular response. We tested this by comparing Amhara and Oromo highlanders at 3,700 and 4,000 m to their lowland counterparts at 1,200 and 1,700 m. To evaluate vascular responses, we assessed urinary levels of nitrate (NO3−) as a readout of production of the vasodilator nitric oxide and its downstream signal transducer cyclic guanosine monophosphate (cGMP), along with diastolic blood pressure as an indicator of vasomotor tone. To evaluate hematological responses, we measured hemoglobin and percent oxygen saturation of hemoglobin. Amhara highlanders, but not Oromo, had higher NO3−and cGMP compared with their lowland counterparts. NO3−directly correlated with cGMP (Amhara R2= 0.25, P < 0.0001; Oromo R2= 0.30, P < 0.0001). Consistent with higher levels of NO3−and cGMP, diastolic blood pressure was lower in Amhara highlanders. Both highland samples had apparent left shift in oxyhemoglobin saturation characteristics and maintained total oxyhemoglobin content similar to their lowland counterparts. However, deoxyhemoglobin levels were significantly higher, much more so among Oromo than Amhara. In conclusion, the Amhara balance minimally elevated hemoglobin with vasodilatory response to environmental hypoxia, whereas Oromo rely mainly on elevated hemoglobin response. These results point to different combinations of adaptive responses in genetically similar East African highlanders.
Heat induces interleukin-6 in skeletal muscle cells via TRPV1/PKC/CREB pathways
Authors: Obi Syotaro , Nakajima Toshiaki , Hasegawa Takaaki , Kikuchi Hironobu , Oguri Gaku , Takahashi Masao , Nakamura Fumitaka , Yamasoba Tatsuya , Sakuma Masashi , Toyoda Shigeru , Tei Chuwa , Inoue Teruo
Published: December 2016

Interleukin-6 (IL-6) is released from skeletal muscle cells and induced by exercise, heat, catecholamine, glucose, lipopolysaccharide, reactive oxygen species, and inflammation. However, the mechanism that induces release of IL-6 from skeletal muscle cells remains unknown. Thermosensitive transient receptor potential (TRP) proteins such as TRPV1–4 play vital roles in cellular functions. In this study we hypothesized that TRPV1 senses heat, transmits a signal into the nucleus, and produces IL-6. The purpose of the present study is to investigate the underlying mechanisms whereby skeletal muscle cells sense and respond to heat. When mouse myoblast cells were exposed to 37–42°C for 2 h, mRNA expression of IL-6 increased in a temperature-dependent manner. Heat also increased IL-6 secretion in myoblast cells. A fura 2 fluorescence dual-wavelength excitation method showed that heat increased intracellular calcium flux in a temperature-dependent manner. Intracellular calcium flux and IL-6 mRNA expression were increased by the TRPV1 agonists capsaicin and N-arachidonoyldopamine and decreased by the TRPV1 antagonists AMG9810 and SB366791 and siRNA-mediated knockdown of TRPV1. TRPV2, 3, and 4 agonists did not change intracellular calcium flux. Western blotting with inhibitors demonstrated that heat increased phosphorylation levels of TRPV1, followed by PKC and cAMP response element-binding protein (CREB). PKC inhibitors, Gö6983 and staurosporine, CREB inhibitors, curcumin and naphthol AS-E, and knockdown of CREB suppressed the heat-induced increases in IL-6. These results indicate that heat increases IL-6 in skeletal muscle cells through the TRPV1, PKC, and CREB signal transduction pathway.

NEW & NOTEWORTHY Heat increases the release of interleukin-6 (IL-6) from skeletal muscle cells. IL-6 has been shown to serve immune responses and metabolic functions in muscle. It can be anti-inflammatory as well as proinflammatory. However, the mechanism that induces release of IL-6 from skeletal muscle cells remains unknown. Here we show that heat increases IL-6 in skeletal muscle cells through the transient receptor potential vannilloid 1, PKC, and cAMP response element-binding protein signal transduction pathway.
Role of calpain in eccentric contraction-induced proteolysis of Ca2+-regulatory proteins and force depression in rat fast-twitch skeletal muscle
Authors: Kanzaki Keita , Watanabe Daiki , Kuratani Mai , Yamada Takashi , Matsunaga Satoshi , Wada Masanobu
Published: December 2016

The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca2+-regulatory proteins and force production in fast-twitch skeletal muscles. Rat extensor digitorum longus muscles were exposed to 200 repeated ECC in situ and excised immediately [recovery 0 (REC0)] or 3 days [recovery 3 (REC3)] after cessation of ECC. Calpain inhibitor (CI)-treated rats were intraperitoneally injected with MDL-28170 before ECC and during REC3. Tetanic force was markedly reduced at REC0 and remained reduced at REC3. CI treatment ameliorated the ECC-induced force decline but only at REC3. No evidence was found for proteolysis of dihydropyridine receptor (DHPR), junctophilin (JP)1, JP2, ryanodine receptor (RyR), sarcoplasmic reticulum Ca2+-ATPase (SERCA)1a, or junctional face protein-45 at REC0. At REC3, ECC resulted in decreases in DHPR, JP1, JP2, RyR, and SERCA1a. CI treatment prevented the decreases in DHPR, JP1, and JP2, whereas it had little effect on RyR and SERCA1a. These findings suggest that DHPR, JP1, and JP2, but not RyR and SERCA1a, undergo calpain-dependent proteolysis in in vivo muscles subjected to ECC and that impaired function of DHPR and/or JP might cause prolonged force deficits with ECC.

NEW & NOTEWORTHY Calpain-dependent proteolysis is one of the contributing factors to muscle damage that occurs with eccentric contraction (ECC). It is unclear, however, whether calpains account for proteolysis of Ca2+-regulatory proteins in in vivo muscles subjected to ECC. Here, we provide evidence that dihydropyridine receptor and junctophilin, but not ryanodine receptor and sarcoplasmic reticulum Ca2+-ATPase, undergo calpain-dependent proteolysis.
Some Differential Geometric Relations in the Elastic Shell
Authors: Shen Xiaoqin , Li Haoming , Li Kaitai , Cao Xiaoshan , Yang Qian
Published: December 2016

The theory of the elastic shells is one of the most important parts of the theory of solid mechanics. The elastic shell can be described with its middle surface; that is, the three-dimensional elastic shell with equal thickness comprises a series of overlying surfaces like middle surface. In this paper, the differential geometric relations between elastic shell and its middle surface are provided under the curvilinear coordinate systems, which are very important for forming two-dimensional linear and nonlinear elastic shell models. Concretely, the metric tensors, the determinant of metric matrix field, the Christoffel symbols, and Riemann tensors on the three-dimensional elasticity are expressed by those on the two-dimensional middle surface, which are featured by the asymptotic expressions with respect to the variable in the direction of thickness of the shell. Thus, the novelty of this work is that we can further split three-dimensional mechanics equations into two-dimensional variation problems. Finally, two kinds of special shells, hemispherical shell and semicylindrical shell, are provided as the examples.
Identification of Gingival Crevicular Fluid Sampling, Analytical Methods, and Oral Biomarkers for the Diagnosis and Monitoring of Periodontal Diseases: A Systematic Review
Authors: Nazar Majeed Zeyad , Philip Koshy , Alabsi A. M. , Pushparajan Saravanan , Swaminathan Dasan
Published: December 2016

Background. Several studies in the last decades have focused on finding a precise method for the diagnosis of periodontal disease in its early stages.Aim. To evaluate from current scientific literature the most common and precise method for gingival crevicular fluid (GCF) sample collection, biomarker analytical methods, and the variability of biomarker quantification, even when using the same analytical technique.Methodology. An electronic search was conducted on in vivo studies that presented clinical data on techniques used for GCF collection and biomarker analysis.Results. The results showed that 71.1%, 24.7%, and 4.1% of the studies used absorption, microcapillary, and washing techniques, respectively, in their gingival crevicular fluid collection. 73.1% of the researchers analyzed their samples by using enzyme-linked immunosorbent assay (ELISA). 22.6%, 19.5%, and 18.5% of the researchers included interleukin-1 beta (IL-1β), matrix metalloproteinase-8 (MMP-8), and tumor necrosis factor-alpha (TNF-α), respectively, in their studies as biomarkers for periodontal disease.Conclusion. IL-1βcan be considered among the most common biomarkers that give precise results and can be used as an indicator of periodontal disease progression. Furthermore, paper strips are the most convenient and accurate method for gingival crevicular fluid collection, while enzyme-linked immunosorbent assay can be considered the most conventional method for the diagnosis of biofluids.
Parameter Extraction of Solar Photovoltaic Modules Using Gravitational Search Algorithm
Authors: Sarjila R. , Ravi K. , Belwin Edward J. , Kumar K. Sathish , Prasad Avagaddi
Published: December 2016

Parameter extraction of a solar photovoltaic system is a nonlinear problem. Many optimization algorithms are implemented for this purpose, which failed in giving better results at low irradiance levels. This article presents a novel method for parameter extraction using gravitational search algorithm. The proposed method evaluates the parameters of different PV panels at various irradiance levels. A critical evaluation and comparison of gravitational search algorithm with other optimization techniques such as genetic algorithm are given. Extensive simulation analyses are carried out on the proposed method and show that GSA is much suitable for parameter extraction problem.
The Signaling Pathways Involved in Chondrocyte Differentiation and Hypertrophic Differentiation
Authors: Li Jianmei , Dong Shiwu
Published: December 2016

Chondrocytes communicate with each other mainly via diffusible signals rather than direct cell‐to‐cell contact. The chondrogenic differentiation of mesenchymal stem cells (MSCs) is well regulated by the interactions of varieties of growth factors, cytokines, and signaling molecules. A number of critical signaling molecules have been identified to regulate the differentiation of chondrocyte from mesenchymal progenitor cells to their terminal maturation of hypertrophic chondrocytes, including bone morphogenetic proteins (BMPs), SRY‐related high‐mobility group‐box gene 9 (Sox9), parathyroid hormone‐related peptide (PTHrP), Indian hedgehog (Ihh), fibroblast growth factor receptor 3 (FGFR3), and β‐catenin. Except for these molecules, other factors such as adenosine, O2 tension, and reactive oxygen species (ROS) also have a vital role in cartilage formation and chondrocyte maturation. Here, we outlined the complex transcriptional network and the function of key factors in this network that determine and regulate the genetic program of chondrogenesis and chondrocyte differentiation.
Analysis of Density Wave Oscillations in Helically Coiled Tube Once-Through Steam Generator
Authors: Hao Junwei , Zhang Yaoli , Zheng Jianxiang , Zhou Zhiwei , Sheng Xuanyu , Hong Gang , Ye Kai , Li Ning
Published: December 2016

Helically coiled tube Once-Through Steam Generator (H-OTSG) is one of the key equipment types for small modular reactors. The flow instability of the secondary side of the H-OTSG is particularly serious, because the working condition is in the range of low and medium pressure. This paper presents research on density wave oscillations (DWO) in a typical countercurrent H-OTSG. Based on the steady-state calculation, the mathematical model of single-channel system was established, and the transfer function was derived. Using Nyquist stability criterion of the single variable, the stability cases were studied with an in-house computer program. According to the analyses, the impact law of the geometrical parameters to the system stability was obtained. RELAP5/MOD3.2 code was also used to simulate DWO in H-OTSG. The theoretical analyses of the in-house program were compared to the simulation results of RELAP5. A correction factor was introduced to reduce the error of RELAP5 when modeling helical geometry. The comparison results agreed well which showed that the correction is effective.
Early Effector T Lymphocytes Coexpress Multiple Inhibitory Receptors in Primary Non–Small Cell Lung Cancer
Authors: Tassi Elena , Grazia Giulia , Vegetti Claudia , Bersani Ilaria , Bertolini Giulia , Molla Alessandra , Baldassari Paola , Andriani Francesca , Roz Luca , Sozzi Gabriella , Pastorino Ugo , Mortarini Roberta , Anichini Andrea
Published: December 2016

Clinical efficacy of PD-1/PD-L1 targeting relies upon the reactivation of tumor-specific but functionally impaired PD-1+ T cells present before therapy. Thus, analyzing early-stage primary tumors may reveal the presence of T cells that are not yet functionally impaired. In this study, we report that activated (HLA-DR+) T cells with an effector memory (TEM) profile are enriched in such lesions. Tumor-infiltrating lymphocytes coexpressed PD-1 with the inhibitory receptors TIM-3, CTLA-4, LAG-3, and TIGIT, but also displayed a recently activated, nonexhausted phenotype. We also identified a subset of CD8+PD-1+FOXP3+ T lymphocytes at the earliest phase of functional differentiation after priming, termed “early effector cells” (EEC), which also exhibited an activated nonexhausted phenotype, but was less differentiated and associated with coexpression of multiple inhibitory receptors. In response to autologous tumor, EECs upregulated CD107a, produced IL2 and IFNγ, and were competent for differentiation. The identification of EECs marked by inhibitory receptor expression at tumor sites will enable investigations of early stages of adaptive antitumor immunity, as well as support the rationale for administering immunotherapy in early-stage non–small cell lung cancer. Cancer Res; 77(4); 851–61. ©2016 AACR.
Cytotoxic T Cells and Granzyme B Associated with Improved Colorectal Cancer Survival in a Prospective Cohort of Older Women
Authors: Prizment Anna E. , Vierkant Robert A. , Smyrk Thomas C. , Tillmans Lori S. , Nelson Heather H. , Lynch Charles F. , Pengo Thomas , Thibodeau Stephen N. , Church Timothy R. , Cerhan James R. , Anderson Kristin E. , Limburg Paul J.
Published: December 2016

Background: Host immune response may predict the course of colorectal cancer. We examined the survival of 468 colorectal cancer patients associated with two tumor-infiltrating immune biomarkers, the number of cytotoxic T lymphocytes (CTLs), and the activated CTLs, as reflected by the number of cells expressing granzyme B (GZMB) in the prospective Iowa Women's Health Study.

Methods: Using paraffin-embedded tissue samples, we constructed and immunostained tumor microarrays with CD8 (for CTL) and GZMB antibodies. We scored CTL and GZMB densities in tumor epithelial and stromal tissues and also created a composite score for each biomarker (sum of the scores across tissue compartments). Cox regression estimated the HR and 95% confidence intervals (CI) for all-cause and colorectal cancer–specific death associated with each composite score.

Results: CTL and GZMB composite scores were positively correlated (r = 0.65) and each biomarker was inversely correlated with stage at diagnosis. Both composite scores were higher in proximal colon tumors and tumors characterized by MSI-high, CIMP-high, or BRAF mutation status. HRs (95% CI) were 0.53 (0.38–0.75; Ptrend = 0.0004) and 0.66 (0.51–0.86; Ptrend = 0.002) for all-cause death, respectively, and 0.30 (0.18–0.51; Ptrend < 0.0001) and 0.41 (0.27–0.63; Ptrend < 0.0001) for colorectal cancer–related death, respectively. Including CTL and GZMB scores simultaneously in the model significantly improved the predictive performance of the models for all-cause and colorectal cancer–related death.

Conclusions: Higher tumor infiltration with CTL and GZMB cells is associated with improved all-cause and cancer-specific survival of colorectal cancer patients.

Impact: Both the number of CTLs and GZMB appear to be useful prognostic factors in colorectal cancer, irrespective of stage. Cancer Epidemiol Biomarkers Prev; 26(4); 622–31. ©2016 AACR.
The mTORC1/2 Inhibitor AZD8055 Strengthens the Efficiency of the MEK Inhibitor Trametinib to Reduce the Mcl-1/[Bim and Puma] ratio and to Sensitize Ovarian Carcinoma Cells to ABT-737
Authors: Pétigny-Lechartier Cécile , Duboc Charlène , Jebahi Abdelghani , Louis Marie-Hélène , Abeilard Edwige , Denoyelle Christophe , Gauduchon Pascal , Poulain Laurent , Villedieu Marie
Published: December 2016

The identification of novel therapeutic strategies is an important urgent requirement for the clinical management of ovarian cancer, which remains the leading cause of death from gynecologic cancer. Several studies have shown that the antiapoptotic proteins Bcl-xL and Mcl-1, as well as the proapoptotic protein Bim, are key elements to be modulated to kill ovarian cancer cells. Pharmacologic inhibition of Bcl-xL is possible by using BH3-mimetic molecules like ABT-737. However, inhibition of Mcl-1 and/or promotion of its BH3-only partners (including Bim, Puma, and Noxa) remains a challenge that may be achieved by modulating the signaling pathways upstream. This study sought whether AZD8055-induced mTOR inhibition and/or trametinib-induced MEK inhibition could modulate Mcl-1 and its partners to decrease the Mcl-1/BH3-only ratio and thus sensitize various ovarian cancer cell lines to ABT-737. AZD8055 treatment inhibited Mcl-1 and increased Puma expression but did not induce massive apoptosis in combination with ABT-737. In contrast, trametinib, which decreased the Mcl-1/BH3-only protein ratio by upregulating Puma and dephosphorylated active Bim, sensitized IGROV1-R10 and OVCAR3 cells to ABT-737. Adding AZD8055 to trametinib further reduced the Mcl-1/BH3-only protein ratio and triggered apoptosis without ABT-737 in IGROV1-R10 cells. Moreover, the AZD8055/trametinib association highly sensitized all cell lines including SKOV3 to ABT-737, the induced dephosphorylated Bim being crucial in this sensitization. Finally, the three-drug combination was also very efficient when replacing AZD8055 by the pan-Akt inhibitor MK-2206. This study thus proposes original multitargeted strategies and may have important implications for the design of novel approaches for ovarian cancer treatment. Mol Cancer Ther; 16(1); 102–15. ©2016 AACR.
Pigs with Severe Combined Immunodeficiency Are Impaired in Controlling Influenza A Virus Infection
Authors: Rajao Daniela S. , Loving Crystal L. , Waide Emily H. , Gauger Phillip C. , Dekkers Jack C.M. , Tuggle Christopher K. , Vincent Amy L.
Published: December 2016

Influenza A viruses (IAV) infect many host species, including humans and pigs. Severe combined immunodeficiency (SCID) is a condition characterized by a deficiency of T, B, and/or natural killer (NK) cells. Animal models of SCID have great value for biomedical research. Here, we evaluated the pathogenesis and the innate immune response to the 2009 H1N1 pandemic IAV (H1N1pdm09) using a recently identified line of naturally occurring SCID pigs deficient in T and B lymphocytes that still have functional NK cells. SCID pigs challenged with H1N1pdm09 showed milder lung pathology compared to the non-SCID heterozygous carrier pigs. Viral titers in the lungs and nasal swabs of challenged SCID pigs were significantly higher than in carrier pigs 7 days postinfection, despite higher levels of IL-1β and IFN-α in the lungs of SCID pigs. The lower levels of pulmonary pathology were associated with the T and B cell absence in response to infection. The higher viral titers, prolonged shedding, and delayed viral clearance indicated that innate immunity was insufficient for controlling IAV in pigs. This recently identified line of SCID pigs provides a valuable model to understand the immune mechanisms associated with influenza protection and recovery in a natural host.
In the Era of Therapeutic Hypothermia, How Well Do Studies of Perinatal Neuroprotection Control Temperature?
Authors: Galinsky Robert , Dean Justin M. , Lear Christopher A. , Davidson Joanne O. , Dhillon Simerdeep , Wassink Guido , Bennet Laura , Gunn Alistair J.
Published: December 2016

In the era of therapeutic hypothermia, reliable preclinical studies are integral to successfully identify neuroprotective strategies to further improve outcomes of encephalopathy at term. We reviewed preclinical neuroprotection studies reported between January 2014 and June 2016 to assess the use of effective temperature monitoring and control. As a secondary measure, we examined whether studies addressed other methodological issues such as stage of brain development, sex differences, the timing of the treatment relative to the insult, and the histological and functional endpoints used after hypoxia-ischemia. The extent and duration of temperature monitoring was highly inconsistent. Only a minority of papers monitored core (19/61; 31%) or brain temperature (3/61; 5%). Most (40/45) of the neuroprotectants either were likely to affect thermoregulation or their impact is unknown. In 85% of papers neonatal rodents were used (67% at P7); 51% of papers did not report the sex of the animals or tested the effect of potential neuroprotectants on just one sex. In 76% of studies, treatment was before or immediately after the insult (within the first 2 h), and few studies assessed long-term histological and behavioral outcomes. In conclusion, many recent preclinical neonatal studies cannot exclude the possibility that apparent neuroprotection might be related to drug-induced hypothermia or to other methodological choices. Close monitoring and control of brain temperature during, as well as for many days after, experimental hypoxia-ischemia are now critical to reliably develop new ways to improve neurodevelopmental outcomes after perinatal hypoxic-ischemic encephalopathy.
Prognostic Significance of Dementia in Older Adults with Solid Tumors
Authors: Wongrakpanich Supakanya , Hurst Amy , Bustamante Jean , Candelario Nellowe , Biso Sylvia , Chaiwatcharayut Wikrom , Dourado Claudia , Rosenzweig Andrew
Published: December 2016

Background: The public health burden of cancer and dementia in the geriatric population is well documented. There is limited data on how dementia predicts mortality among geriatric patients with solid tumors. The objective of this study is to determine the prognostic significance of dementia on survival in patients with solid tumors. Methods: We performed a 5-year retrospective study on elderly subjects aged ≥60 years with and without dementia that were diagnosed with solid tumors. Results: Among 3,460 patients with solid tumors, 132 (3.8%) patients were found to have dementia. The median age at diagnosis was 71 years. Kaplan-Meier curves demonstrated that patients with dementia had an inferior median survival compared to the nondemented group (30 vs. 56 months; log-rank p < 0.001). Cox proportional hazard regression modeling identified age >80 years, female gender, diabetes mellitus, congestive heart failure, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, dementia, and radiation therapy as risk factors for decreased overall survival. Conclusions: We demonstrated that dementia is associated with shorter overall survival in elderly patients with solid tumors.
2016 Russell Ross Memorial Lecture in Vascular Biology
Authors: Tabas Ira
Published: December 2016

Atherosclerosis is initiated by the subendothelial accumulation of apoB-lipoproteins, which initiates a sterile inflammatory response dominated by monocyte–macrophages but including all classes of innate and adaptive immune cells. These inflammatory cells, together with proliferating smooth muscle cells and extracellular matrix, promote the formation of subendothelial lesions or plaques. In the vast majority of cases, these lesions do not cause serious clinical symptoms, which is due in part to a resolution–repair response that limits tissue damage. However, a deadly minority of lesions progress to the point where they can trigger acute lumenal thrombosis, which may then cause unstable angina, myocardial infarction, sudden cardiac death, or stroke. Many of these clinically dangerous lesions have hallmarks of defective inflammation resolution, including defective clearance of dead cells (efferocytosis), necrosis, a defective scar response, and decreased levels of lipid mediators of the resolution response. Efferocytosis is both an effector arm of the resolution response and an inducer of resolution mediators, and thus its defect in advanced atherosclerosis amplifies plaque progression. Preclinical causation/treatment studies have demonstrated that replacement therapy with exogenously administered resolving mediators can improve lesional efferocytosis and prevent plaque progression. Work in this area has the potential to potentiate the cardiovascular benefits of apoB-lipoprotein–lowering therapy.
Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association
Authors: Smith Eric E. , Saposnik Gustavo , Biessels Geert Jan , Doubal Fergus N. , Fornage Myriam , Gorelick Philip B. , Greenberg Steven M. , Higashida Randall T. , Kasner Scott E. , Seshadri Sudha
Published: December 2016

Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians.
Three-Dimensional Map of Neonatal Arterial Ischemic Stroke Distribution From Early Multimodal Brain Imaging
Authors: Stephan-Otto Christian , Núñez Christian , Arca Gemma , Agut Thais , García-Alix Alfredo
Published: December 2016

Background and Purpose—

Although neonatal arterial ischemic stroke (NAIS) location has considerable impact on long-term outcome, a map showing spatial distribution of NAIS is lacking. Our aim was to generate this distribution map, based on early magnetic resonance imaging data.

Methods—

Lesions from 34 consecutive neonates with NAIS from a single center were segmented using multimodal magnetic resonance imaging (median age at acquisition =5 days). Lesion masks for all subjects were registered onto a standard neonatal brain and then overlaid to generate a 3D map of NAIS distribution.

Results—

The region posterior to the central sulcus is the most frequently affected in neonates, with 24 of the 34 neonates (71%) showing lesions in this region in at least one hemisphere. Moreover, NAIS frequency is markedly higher in the left hemisphere.

Conclusions—

This is the first report of an NAIS distribution map. Regions posterior to the central sulcus present increased vulnerability. Our findings suggest that motor areas are not as frequently affected as has been previously reported. By contrast, we find high NAIS vulnerability in functional areas related to language. The distribution of ischemic strokes in neonates seems to be different from that seen in adults.
Onosma juliae (Boraginaceae), a new species from southern Turkey, with remarks on the systematics of Onosma in the Irano-Turanian region
Authors: CECCHI LORENZO , COPPI ANDREA , SELVI FEDERICO
Published: December 2016

The new species Onosma juliae is described and illustrated based on specimens collected in the westernmost part of the Taurus range in southern Anatolia (Turkey, Karaman province). Differences with the putatively more closely related species are briefly discussed, and a synthetic but comprehensive key to the Irano-Turanian members of the genus known to date is provided to allow the identification of the major species group.
Pterocladiella maribagoensis (Gelidiales, Rhodophyta), a new marine alga from Cebu, Philippines
Authors: BOO GA HUN , GERALDINO PAUL JOHN L.
Published: December 2016

A new species of marine gelidioid red algae, Pterocladiella maribagoensis, is described and illustrated. Pterocladiella maribagoensis is distinguished by small, terete to compressed thalli with alternate or irregular branches, peg-like haptera, rhizines in medulla, and tetrasporangial sori without sterile margin at the terminal of branches. Analyses of both mitochondrial cox1 and plastid rbcL sequences revealed that P. maribagoensis was distinct from other species of Pterocladiella and clustered with P. australafricanensis, P. beachiae, P. caerulescens, P. phangiae, and P. psammophila. Morphological differences between P. maribagoensis and similar species are presented.
Australian mycophagous species of the genus Deplorothrips (Thysanoptera, Phlaeothripinae)
Authors: MOUND LAURENCE A. , TREE DESLEY J.
Published: December 2016

The genus Deplorothrips Mound & Walker is recorded from Australia for the first time. The genus is found widely across the continent, and descriptions and an illustrated identification key are provided to 14 new species. These have been found living on dead twigs and branches, particularly of Eucalyptus trees. Typical members of this genus have short maxillary stylets that are scarcely retracted into the head capsule, but some of the species have more deeply retracted stylets. Structural polymorphism is recorded in several species, associated both with sex and with body size. Remarkable variation is recorded for some species in the number of sense cones on the antennal segments.