bluuebunny/crossref_metadata_2025 huggingface dataset:
Indexing recruitment for source populations contributing to mixed fisheries by incorporating age in genetic stock identification models
Authors: Brenden Travis O. , Tsehaye Iyob , Bence James R. , Kanefsky Jeannette , Scribner Kim T.
Published: August 2017

We describe a methodology for estimating relative recruitments for source populations (sources) contributing to mixed fisheries by incorporating age into genetic stock identification models. The approach produced recruitment estimates that were strongly correlated (median correlation = 0.849; 2.5 and 97.5 percentile in correlations = 0.613 and 0.951, respectively) with simulated recruitments across various design factors, including number of sources, genetic divergence among sources, and temporal variation in source recruitments. Sensitivity analyses indicated that the approach was robust to aging inaccuracies and assumed source mortalities. Application to walleye (Sander vitreus) sources contributing to the Saginaw Bay, Lake Huron, fishery produced similar recruitment estimates to assessment models. There was greater discrepancy between recruitment estimates for lake trout (Salvelinus namaycush) hatchery strains in northern Lake Michigan when compared with strain stocking levels, although this mismatch may stem from stocking levels being a poor recruitment measure. The estimation approach should prove beneficial for indexing source recruitment based on fishery or assessment collections from mixtures, even when long-term time series of harvest and survey data required for integrated assessments are not available.
Dysregulated mitogen-activated protein kinase and matrix metalloproteinase in ethanol-induced cavernosal dysfunction
Authors: Muniz Jaqueline J. , Leite Letícia N. , Lacchini Riccardo , Tanus-Santos José E. , Tirapelli Carlos R.
Published: August 2017

We evaluated the effects of ethanol consumption on the mitogen-activated protein kinases (MAPK) and metalloproteinases (MMP) pathways in the rat cavernosal smooth muscle (CSM). Male Wistar rats were treated with ethanol (20% v/v) for 6 weeks. Quantitative real-time polymerase chain reaction experiments showed that ethanol consumption did not alter mRNA levels of p38MAPK, SAPK/JNK, ERK1/2, MMP-2, or MMP-9 in the rat CSM. Western immunoblotting experiments revealed decreased protein expression of p38MAPK and phosphorylation of SAPK/JNK in the CSM from ethanol-treated rats. Additionally, ethanol consumption decreased the expression of MMP-2. Functional assays showed that SP600125, an inhibitor of SAPK/JNK, prevented the increase in endothelin (ET)-1-induced contraction in the CSM from ethanol-treated rats. Treatment with ethanol decreased MMP-2 activity, but did not change net MMP activity in the rat CSM. Ethanol consumption increased the circulating levels of MMP-2, MMP-9, and TIMP-2 as well as the MMP-9/TIMP-1 ratio. The major finding of our study is that ethanol consumption down-regulates both MAPK and MMP pathways in the rat CSM, whereas it increases the circulating levels of MMP-9. Additionally, we found that SAPK/JNK plays a role in ethanol-induced increase on ET-1 contraction in the isolated rat CSM.
Impact of High-k Spacer on Device Performance of Nanoscale Underlap Fully Depleted SOI MOSFET
Authors: Sharma Rajneesh , Rathore Rituraj S. , Rana Ashwani K.
Published: August 2017

The fully depleted Silicon-On-Insulator MOSFETs (FD-SOI) have shown high immunity to short channel effects compared to conventional bulk MOSFETs. The inclusion of gate underlap in SOI structure further improves the device performance in nanoscale regime by reducing drain induced barrier lowering and leakage current ([Formula: see text]). However, the gate underlap also results in reduced ON current ([Formula: see text]) due to increased effective channel length. The use of high-[Formula: see text] material as a spacer region helps to achieve the higher [Formula: see text] but at the cost of increased effective gate capacitance ([Formula: see text]) which degrades the device performance. Thus, the impact of high-[Formula: see text] spacer on the performance of underlap SOI MOSFET (underlap-SOI) is studied in this paper. To fulfil this objective, we have analyzed the performance parameters such as [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]/[Formula: see text] ratio and intrinsic transistor delay (CV/I) with respect to the variation of device parameters. Various dielectric materials are compared to optimize the [Formula: see text]/[Formula: see text] ratio and CV/I for nanoscale underlap-SOI device. Results suggest that the HfO2 of 10[Formula: see text]nm length is optimum value to enhance device performance. Further, the higher underlap length is needed to offset the exponential increase in [Formula: see text] especially below 20[Formula: see text]nm gate length.
ESTIMATION OF INTRAUTERINE PRESSURE FROM ELECTROHYSTEROGRAPHY USING HILBERT PHASE SLIPS AND STATISTICS METHOD
Authors: YANG ZIDUO , YANG RENHUAN , LU YAOSHENG
Published: August 2017

Prognostic information during pregnancy can be obtained by monitoring maternal uterine activity. Tocodynamometry (TOCO) is widely used to assess the uterine activity today but it has been found that it has very low sensitivity. Another method to assess the uterine activity is intrauterine pressure catheter (IUPC) which is accurate but highly invasive. Electrohysterogram (EHG) measured from abdominal surface is a noninvasive method to detect uterine contractions. To reduce motion artifacts of intrauterine pressure (IUP) estimated from EHG signal and further improve the accuracy of contractions detected by IUP estimation, we propose a method to divide the EHG signal into segments by using Hilbert phase slips. Standard deviation (STD) was used to estimate IUP from each EHG signal segment and median filter was used to remove the motion artifacts. The method we proposed was compared with other four methods from literatures. The proposed method results in a higher contractions detection accuracy of EHG-based IUP estimation and a higher correlation coefficient with the IUPC signals compared to other methods which demonstrated the capabilities of the proposed method in reducing motion artifacts of IUP estimation based on abdominal EHG.
Silicon(IV) phthalocyanine-biotin conjugates: Synthesis, photophysicochemical properties and in vitro biological activity for photodynamic therapy
Authors: Gülmez Asuman Dakoğlu , Göksel Meltem , Durmuş Mahmut
Published: August 2017

Silicon (IV) phthalocyanines bearing one or two biotin groups on the axially positions were synthesized, and these novel phthalocyanines were characterized by elemental analysis and standard spectroscopic techniques such as FT-IR, [Formula: see text]H NMR, UV-vis and MALDI-TOF. The synthesized compounds are the first examples of axially biotin substituted silicon (IV) phthalocyanines. These phthalocyanines were designed as targeting photosensitizers for the treatment of cancer by photodynamic therapy (PDT) technique. The phthalocyanine ring was selected for its photosensitizer ability and the biotin group was selected as a targeting agent for increasing accumulation of these photosensitizers in tumor cells. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen generation) properties of the target silicon(IV) phthalocyanines were investigated in DMSO. The photosensitizing efficiency of the studied phthalocyanines was tested against human cervical cancer (HeLa) cells at different photosensitizer concentrations. Both axially mono- and bis-biotin substituted silicon(IV) phthalocyanines present high photocytotoxicity against HeLa cancer cells with the cell survival degree ranging from 13% to 50%. The photosensitivity and the intensity of damage were found to be directly related to the concentration of the used photosensitizers. According to the obtained results, both silicon(IV) phthalocyanine derivatives could be promising as photosensitizers for treatment of cancer by PDT technique.
Optical limiting properties of 2,6-dibromo-3,5- distyrylBODIPY dyes at 532 nm
Authors: Kubheka Gugu , Mack John , Kobayashi Nagao , Kimura Mitsumi , Nyokong Tebello
Published: August 2017

Optical limiting properties of 2,6-dibromo-3,5-distyrylBODIPY dyes were investigated by using the z-scan technique at 532 nm in the nanosecond pulse range. A strong reverse saturable absorption response was observed even in solution, which suggests that compounds of this type are potentially suitable for use in optical limiting applications.
Seismic Vulnerability Assessment of Steel Moment-Resisting Frames Based on Local Damage
Authors: Vahdani Reza , Gerami Mohsen , Razi Morteza
Published: August 2017

This paper investigates the seismic vulnerability of steel moment-resisting frames (SMRFs) based on plasticity development in structural components. Pushover analyses with three different lateral load patterns are performed to identify the location of plastic hinges at the collapse state and IDA analysis is employed to find the seismic intensities causing the formation of the specified hinges. An ensemble of 30 near-fault pulse-like motions classified into three groups of short, medium and long period motions and ten ordinary ground motions are used for seismic loading on five sample frames with 3 to 15 stories. Employing this method, the interstory drift ratio coincident to the seismic collapse is evaluated. Then, the critical pulse period producing the most damage to the structures is estimated. Finally, fragility curves are developed for near- and far-fault excitations. The results indicate that maximum interstory drift ratio at the collapse state of the frames ranges from 1.5% to 10%. It is also found that the ratio of critical pulse period to natural period of SMRF structures is between 2.3 and 2.9. Moreover, the fragility analysis reveals that collapse intensity equivalent to 10% of exceedence for near-fault motions is 70% to 85% less than far-fault records.
Race, Law, and Inequality, 50 Years After the Civil Rights Era
Authors: Munger Frank W. , Seron Carroll
Published: August 2017

Over the last several decades, law and social science scholars have documented persistent racial inequality in the United States. This review focuses on mechanisms to explain this persistent pattern. We begin with policy making, a mechanism fundamental to all the others. We then examine one particularly important policy, the carceral state, which can be described as the most important policy response to the civil rights era. A significant body of scholarship on employment discrimination presents a site for explaining the transformation of law on the books into the law in action. Finally, we review scholarship on the persistence of segregation and concentrated neighborhood disadvantage and their attendant impact on racial inequality. We conclude with two themes that deserve special emphasis: the need for theory drawing these fields together and our need, above all at this moment in our history, for public scholarship changing the discourse, politics, and law perpetuating racial inequality.
Short-term arrival strategies for endurance exercise performance at moderate altitude
Authors: Foss Joshua L. , Constantini Keren , Mickleborough Timothy D. , Chapman Robert F.
Published: August 2017

For sea level-based endurance athletes who compete at moderate and high altitudes, many are not logistically able to arrive at altitude weeks before the event to fully acclimatize. For those who can only arrive at altitude the night before competition, we asked if there is a physiological and performance advantage in reducing altitude exposure time to 2 h before competition. On three separate visits, 10 cyclists completed overnight laboratory exposures of: 1) a 14-h exposure to normobaric hypoxia (16.2% O2, simulating 2,500 m; 14H), 2) a 12-h exposure to normoxia, then a 2-h hypoxic exposure (2H), and 3) a 14-h exposure to normoxia (CON). Immediately following each exposure, subjects completed a 20-km cycle ergometry time trial in normoxia (CON) or 16.2% O2(14H and 2H). Measures of plasma volume changes, sleep quality, ventilatory acclimatization, perceived exertion, oxygen uptake, and 20-km time were collected. No significant differences were observed in performance measures or perceived exertion between hypoxic trials. Plasma volume loss was significantly greater during 14H than 2H and CON. No differences in ventilatory acclimatization or sleep quality were observed between trials. Although some divergent 20-km performance responses were observed between 14H and 2H, they were not explained by the physiological measures completed. The data suggest that endurance athletes who are logistically restricted from arriving at altitude more than the evening before competition would not gain an advantage by delaying their arrival until a few hours before the competition, although unique individual responses may ultimately influence optimal arrival strategy.

NEW & NOTEWORTHY For athletes who cannot arrive at altitude multiple days before an endurance competition to properly acclimatize, this study asked if shortening hypoxic exposure time to 2 h before a competition was more advantageous than arrival at altitude the evening before competition. Our data suggest that athletes who cannot arrive at altitude with adequate time for complete acclimatization can choose the short-term arrival strategy that best fits with the logistics of their travel.
Combination Therapy with Bispecific Antibodies and PD-1 Blockade Enhances the Antitumor Potency of T Cells
Authors: Chang Chien-Hsing , Wang Yang , Li Rongxiu , Rossi Diane L. , Liu Donglin , Rossi Edmund A. , Cardillo Thomas M. , Goldenberg David M.
Published: August 2017

The DOCK-AND-LOCK (DNL) method is a platform technology that combines recombinant engineering and site-specific conjugation to create multispecific, multivalent antibodies of defined composition with retained bioactivity. We have applied DNL to generate a novel class of trivalent bispecific antibodies (bsAb), each comprising an anti-CD3 scFv covalently conjugated to a stabilized dimer of different antitumor Fabs. Here, we report the further characterization of two such constructs, (E1)-3s and (14)-3s, which activate T cells and target Trop-2– and CEACAM5-expressing cancer cells, respectively. (E1)-3s and (14)-3s, in the presence of human T cells, killed target cells grown as monolayers at subnanomolar concentrations, with a similar potency observed for drug-resistant cells. Antitumor efficacy was demonstrated for (E1)-3s coadministered with human peripheral blood mononuclear cells (PBMC) in NOD/SCID mice harboring xenografts of MDA-MB-231, a triple-negative breast cancer line constitutively expressing Trop-2 and PD-L1. Growth inhibition was observed following treatment with (E1)-3s or (14)-3s combined with human PBMC in 3D spheroids generated from target cell lines to mimic the in vivo behavior and microenvironment of these tumors. Moreover, addition of an antagonistic anti–PD-1 antibody increased cell death in 3D spheroids and extended survival of MDA-MB-231-bearing mice. These preclinical results emphasize the potential of combining T-cell–redirecting bsAbs with antagonists or agonists that mitigate T-cell inhibition within the tumor microenvironment to improve immunotherapy of solid cancers in patients. They also support the use of 3D spheroids as a predictive alternative to in vivo models for evaluating T-cell functions. Cancer Res; 77(19); 5384–94. ©2017 AACR.
Therapeutic Targeting of the CBP/p300 Bromodomain Blocks the Growth of Castration-Resistant Prostate Cancer
Authors: Jin Lingyan , Garcia Jesse , Chan Emily , de la Cruz Cecile , Segal Ehud , Merchant Mark , Kharbanda Samir , Raisner Ryan , Haverty Peter M. , Modrusan Zora , Ly Justin , Choo Edna , Kaufman Susan , Beresini Maureen H. , Romero F. Anthony , Magnuson Steven , Gascoigne Karen E.
Published: August 2017

Resistance invariably develops to antiandrogen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here, we report that the transcriptional coactivator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth in vitro and in vivo. Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression. Our findings offer a preclinical proof of concept for small-molecule therapies to target the CBP/p300 bromodomain as a strategy to treat castration-resistant prostate cancer. Cancer Res; 77(20); 5564–75. ©2017 AACR.
Telehealth Stroke Dysphagia Evaluation Is Safe and Effective
Authors: Morrell Kate , Hyers Megan , Stuchiner Tamela , Lucas Lindsay , Schwartz Karissa , Mako Jenniffer , Spinelli Kateri J. , Yanase Lisa
Published: August 2017

Background: Rapid evaluation of dysphagia poststroke significantly lowers rates of aspiration pneumonia. Logistical barriers often significantly delay in-person dysphagia evaluation by speech language pathologists (SLPs) in remote and rural hospitals. Clinical swallow evaluations delivered via telehealth have been validated in a number of clinical contexts, yet no one has specifically validated a teleswallow evaluation for in-hospital post-stroke dysphagia assessment. Methods: A team of 6 SLPs experienced in stroke care and a telestroke neurologist designed, implemented, and tested a teleswallow evaluation for acute stroke patients, in which 100 patients across 2 affiliated, urban certified stroke centers were sequentially evaluated by a bedside and telehealth SLP. Inter-rater reliability was analyzed using percent agreement, Cohen's kappa, Kendall's tau-b, and Wilcoxon matched-pairs signed rank tests. Logistic regression models accounting for age and gender were used to test the impact of stroke severity and stroke location on agreement. Results: We found excellent agreement for both liquid (91% agreement; kappa = 0.808; Kendall's tau-b = 0.813, p < 0.001; Wilcoxon signed rank = -0.818, p = 0.417) and solid (87% agreement; kappa = 0.792; Kendall's tau-b = 0.844, p < 0.001; Wilcoxon signed rank = 0.243, p = 0.808) dietary textures. From regression modeling, there is suggestive but inconclusive evidence that higher National Institute of Health Stroke Scale (NIHSS) scores correlate with lower levels of agreement for liquid diet recommendations (OR [95% CI] 0.895 [0.793-1.01]; p = 0.07). There was no impact of NIHSS score for solid diet recommendations and no impact of stroke location on solid or liquid diet recommendations. Qualitatively, we identified professional, logistical, technical, and patient barriers to implementation, many of which resolved with experience over time. Conclusions: Dysphagia evaluation by a remote SLP via telehealth is safe and effective following stroke. We plan to implement teleswallow across our multistate telestroke network as standard practice for poststroke dysphagia evaluation.
Ultrasound-Guided Bipolar Umbilical Cord Occlusion in Complicated Monochorionic Pregnancies: Is There a Learning Curve
Authors: Schou Katrine V. , Jensen Lisa N. , Jørgensen Connie , Søgaard Kirsten , Tabor Ann , Sundberg Karin
Published: August 2017

Introduction: Ultrasound-guided bipolar umbilical cord occlusion (UCO) is used in complicated monochorionic multiple pregnancies in Denmark. The aim of this study was to assess a learning curve in the procedure of UCO. Materials and Methods: One hundred and two monochorionic pregnancies treated with UCO at Rigshospitalet, Denmark between 2004 and 2015 were included. The procedures were divided into period 1 (2004-2009) and period 2 (2010-2015) to determine a learning curve. Primary outcome measure was survival rate. Secondary outcome measures were time from operation to fetal loss and gestational age (GA) at delivery. Results: Period 1 included 59 cases. The median GA at procedure was 19.9 weeks (range 16.7-25.9) and at delivery 34.7 weeks (range 24.3-40.3). Period 2 included 43 cases. The median GA at procedure was 20.7 weeks (range 16.7-27.6) and at delivery 37.3 weeks (range 29.1-40.3). Survival rate increased from 78% (period 1) to 95% (period 2) (p = 0.02). GA at delivery increased as well. Fetal death within 48 h after surgery decreased from 4 (period 1) to 0 (period 2). Discussion: Our results suggest a learning curve in the procedure of UCO with improved outcome on all measures.
Use of a 3D Skull Model to Improve Accuracy in Cranioplasty for Autologous Flap Resorption in a 3-Year-Old Child
Authors: Maduri Rodolfo , Viaroli Edoardo , Levivier Marc , Daniel Roy T. , Messerer Mahmoud
Published: August 2017

Cranioplasty is considered a simple reconstructive procedure, usually performed in a single stage. In some clinical conditions, such as in children with multifocal flap osteolysis, it could represent a surgical challenge. In these patients, the partially resorbed autologous flap should be removed and replaced with a precustomed prosthesis which should perfectly match the expected bone defect. We describe the technique used for a navigated cranioplasty in a 3-year-old child with multifocal autologous flap osteolysis. We decided to perform a cranioplasty using a custom-made hydroxyapatite porous ceramic flap. The prosthesis was produced with an epoxy resin 3D skull model of the patient, which included a removable flap corresponding to the planned cranioplasty. Preoperatively, a CT scan of the 3D skull model was performed without the removable flap. The CT scan images of the 3D skull model were merged with the preoperative 3D CT scan of the patient and navigated during the cranioplasty to define with precision the cranioplasty margins. After removal of the autologous resorbed flap, the hydroxyapatite prosthesis matched perfectly with the skull defect. The anatomical result was excellent. Thus, the implementation of cranioplasty with image merge navigation of a 3D skull model may improve cranioplasty accuracy, allowing precise anatomic reconstruction in complex skull defect cases.
TRPA1 Function in Skeletal Muscle Sensory Neurons Following Femoral Artery Occlusion
Authors: Xing Jihong , Li Jianhua
Published: August 2017

Background/Aims: Transient receptor potential channel A1 (TRPA1) is engaged in amplified autonomic responses evoked by stimulation of muscle afferent nerves in rats with experimental peripheral arterial disease. The purposes of this study were to characterize current responses induced by activation of TRPA1 in dorsal root ganglion (DRG) neurons of control limbs and limbs with femoral artery occlusion. Methods: DRG neurons from rats were labeled by injecting the fluorescence tracer DiI into the hindlimb muscles and whole-cell patch clamp experiments were performed to determine TRPA1 currents. Results: Data show that AITC (a TRPA1 agonist) from the concentrations of 50 µM to 200 µM produces a dose-dependent increase of amplitudes of inward current responses. Notably, the peak current amplitude induced by AITC is significantly larger in DRG neurons of ligated limbs than that in control limbs. AITC-induced current responses are observed in small and medium size DRG neurons, and there is no difference in size distribution of DRG neurons between control limbs and ligated limbs. However, femoral occlusion increases the percentage of the AITC-sensitive DRG neurons as compared to control. AITC-induced currents in DRG neurons are significantly attenuated by exposure to 10 µM of HC-030031, a potent and selective inhibitor of TRPA1, in both control and femoral occlusion groups. In addition, capsaicin (a TRPV1 agonist) evokes a greater increase in the amplitude of AITC-currents in DRG neurons of ligated limbs than that in control limbs. Conclusions: A greater current response with activation of TRPA1 is developed in muscle afferent nerves when hindlimb arterial blood supply is deficient under ischemic conditions; and TRPV1 is partly responsible for augmented TRPA1 responses induced by arterial occlusion.
Spatial and Temporal Analyses of FGF9 Expression During Early Pregnancy
Authors: Šućurović Sandra , Nikolić Tamara , Brosens Jan J. , Mulac-Jericevic Biserka
Published: August 2017

Background: Fibroblast growth factors (FGFs), in complex with their receptors (FGFRs), regulate a broad spectrum of biological functions including cellular proliferation, survival, migration, and differentiation. In human endometrial stromal cells, FGF9 is regulated with estrogen (E). Methods/Results: First, we report that in uterus tissue of ovariectomized wild type mice, FGF9 is present in three isoforms and is regulated with E. Second, we found that during peri-implantation, Fgf9 expression reached its peak at day 4.5 of pregnancy. Immunofluorescence analyses demonstrated overlapping FGF9 and COX2 expression surrounding the blastocyst attachment site. Next, we identified FGF9- and CD31-positive cells as a part of the microvessels; however, expression was localized to a distinct population of cells. Finally, our data showed synchronized, spatial expression of FGF9 on the luminal epithelium with FGFR2 present on the trophectoderm. Conclusion: Our data suggest that FGF9 is a crucial factor required to establish the appropriate microenvironment for successful implantation and the maintenance of pregnancy.
Bifidobacterium Infantis Ameliorates Chemotherapy-Induced Intestinal Mucositis Via Regulating T Cell Immunity in Colorectal Cancer Rats
Authors: Mi Hui , Dong Yan , Zhang Bin , Wang Haonan , Peter Chung C.K. , Gao Ping , Fu Hong , Gao Yajie
Published: August 2017

Background/Aims: Intestinal mucositis (IM) is a commonly encountered side effect in cancer patients receiving chemotherapy. This study aimed to investigate the effect of Bifidobacterium infantis (B. infantis) in attenuating the severity of chemotherapy-induced intestinal mucositis by regulating the T cell subsets in rats with colorectal cancer (CRC). Methods: Thirty male Sprague-Dawley (SD) rats were injected dimethyl hydrazine (DMH) subcutaneously for 10 weeks, and then injected SW480 cells in rectal mucosa to create a CRC model, and the rats were randomly divided into three groups: Control group (saline + saline), Chemotherapy group (saline + 5-FU+Oxaliplatin), B. infantis group (B. infantis + 5-FU+Oxaliplatin). IM was evaluated based on diarrhea severity, intestinal villus height, crypt depth, pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), T cell subsets (CD4+ IL17A+ cells and CD4+ CD25+ Foxp3+ Tregs) and related cytokine profiles. Results: The results showed that the B. infantis group demonstrated a higher body weight (BW) and intestinal villus height and a deeper crypt depth compared to the Chemotherapy group. The level of IL-6, IL-1β and TNF-α which increased by chemotherapy, was lowered by B. infantis administration. Real time reverse transcription- polymerase chain reaction (RT-PCR) showed B. infantis reduced relative expression of Th17 and Th1 cells related cytokines, and increased relative expression of CD4+ CD25+ Foxp3+ Tregs related cytokines. Furthermore, Flow cytometry analysis showed B. infantis reduced CD4+ IL17A+ cells and increased CD4+ CD25+ Foxp3+ Tregs in mesenteric lymph nodes (MLNs) compared to the Chemotherapy group. Conclusion: B. infantis effectively attenuates chemotherapy-induced intestinal mucositis by decreasing Th1 and Th17 response and increasing CD4+ CD25+ Foxp3+ Tregs response.
Adiponectin Inhibits TNF-α-Activated PAI-1 Expression Via the cAMP-PKA-AMPK-NF-κB Axis in Human Umbilical Vein Endothelial Cells
Authors: Chen Yijian , Zheng Yongliang , Liu Liping , Lin Chuanming , Liao Changfeng , Xin Liuyan , Zhong Sisi , Cheng Qilai , Zhang Liqun
Published: August 2017

Background: Tumor necrosis factor (TNF)-α can upregulate the expression of plasminogen activator inhibitor (PAI)-1, an inhibitor of fibrinolysis. Adiponectin (Adp) antagonizes TNF-α by negatively regulating its expression in various tissues. In the present study, the ability of Adp to suppress TNF-α-induced PAI-1 upregulation and the underlying mechanisms were evaluated. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with TNF-α in the presence or absence of Adp, and PAI-1 mRNA and antigen expression, activated signaling pathways, and molecular mechanisms were analyzed by qRT-PCR and ELISA. Results: Adp decreased the TNF-α-induced upregulation of PAI-1 mRNA and protein expression and suppressed TNF-α-induced cAMP-PKA-AMPK inactivation. Adp also suppressed the TNF-α-induced NF-kB binding capability on the PAI-1 promoter. Moreover, these Adp-induced effects were further enhanced or prevented by treatment with the cAMP inhibitor Rp-cAMPs or activator forskolin, respectively. Conclusions: Our data suggest that Adp abrogates TNF-α-activated PAI-1 expression by activating cAMP-PKA-AMPK signaling to suppress NF-kB binding to the PAI-1 promoter in HUVECs. Given the antifibrotic effect of PAI-1 abrogation, Adp may be utilized as a novel agent in the treatment of fibrotic diseases.
Inhibitory Effect of Citalopram on the Pharmacokinetics of Carvedilol in Rats and in vitro Models
Authors: Abrudan Maria Bianca , Muntean Dana Maria , Popa Daniela Saveta , Gheldiu Ana-Maria , Neag Maria Adriana , Vlase Laurian
Published: August 2017

Background/Aims: The aim of this study was to investigate the drug-drug interaction between carvedilol and citalopram based on carvedilol metabolism in vitro and his pharmacokinetics (PKs) in vivo after the oral administration of the single drug and both drugs, and reveal citalopram effects on the PKs of carvedilol. Methods: Each rat was cannulated on the femoral vein, prior to being connected to BASi Culex ABC®. Carvedilol was orally administrated in rats (3.57 mg/kg body weight [b.w.]) in the absence of citalopram or after a pre-treatment with multiple oral doses of citalopram (1.42 mg/kg b.w.). Plasma concentrations of carvedilol were determined using high-performance liquid chromatography-MS at the designated time points after drug administration, and the main PK parameters were calculated by noncompartmental analysis. In addition, effects of citalopram on the metabolic rate of carvedilol were investigated using rat-pooled liver microsome incubation systems. Results: During co-administration, significant increases of the area under the plasma concentration-time curve as well as of the peak plasma concentration were observed. The rat-pooled liver microsome incubation experiment indicated that citalopram could decrease the metabolic rate of carvedilol. Conclusion: Citalopram co-administration led to a significant alteration of carvedilol's PK profile in rats; it also demonstrated, in vitro, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition.
PAI-1 (Plasminogen Activator Inhibitor-1) Expression Renders Alternatively Activated Human Macrophages Proteolytically Quiescent
Authors: Hohensinner Philipp J. , Baumgartner Johanna , Kral-Pointner Julia B. , Uhrin Pavel , Ebenbauer Benjamin , Thaler Barbara , Doberer Konstantin , Stojkovic Stefan , Demyanets Svitlana , Fischer Michael B. , Huber Kurt , Schabbauer Gernot , Speidl Walter S. , Wojta Johann
Published: August 2017

Objective—

Macrophages are versatile immune cells capable of polarizing into functional subsets depending on environmental stimulation. In atherosclerotic lesions, proinflammatory polarized macrophages are associated with symptomatic plaques, whereas Th2 (T-helper cell type 2) cytokine–polarized macrophages are inversely related with disease progression. To establish a functional cause for these observations, we analyzed extracellular matrix degradation phenotypes in polarized macrophages.

Approach and Results—

We provide evidence that proinflammatory polarized macrophages rely on membrane-bound proteases including MMP-14 (matrix metalloproteinase-14) and the serine protease uPA (urokinase plasminogen activator) together with its receptor uPAR for extracellular matrix degradation. In contrast, Th2 cytokine alternatively primed macrophages do not show different proteolytic activity in comparison to unpolarized macrophages and lack increased localization of MMP-14 and uPA receptor to the cell membrane. Nonetheless, they express the highest amount of the serine protease uPA. However, uPA activity is blocked by similarly increased expression of its inhibitor PAI-1 (plasminogen activator inhibitor 1). When inhibiting PAI-1 or when analyzing macrophages deficient in PAI-1, Th2 cytokine–polarized macrophages display the same matrix degradation capability as proinflammatory-primed macrophages. Within atherosclerotic lesions, macrophages positive for the alternative activation marker CD206 express high levels of PAI-1. In addition, to test changed tissue remodeling capacities of alternatively activated macrophages, we used a bleomycin lung injury model in mice reconstituted with PAI-1
−/−
bone marrow. These results supported an enhanced remodeling phenotype displayed by increased fibrosis and elevated MMP activity in the lung after PAI-1 loss.

Conclusions—

We were able to demonstrate matrix degradation dependent on membrane-bound proteases in proinflammatory stimulated macrophages and a forced proteolytical quiescence in alternatively polarized macrophages by the expression of PAI-1.
Paradigm of Biased PAR1 (Protease-Activated Receptor-1) Activation and Inhibition in Endothelial Cells Dissected by Phosphoproteomics
Authors: van den Eshof Bart L. , Hoogendijk Arie J. , Simpson Pelle J. , van Alphen Floris P.J. , Zanivan Sara , Mertens Koen , Meijer Alexander B. , van den Biggelaar Maartje
Published: August 2017

Objective—

Thrombin is the key serine protease of the coagulation cascade and mediates cellular responses by activation of PARs (protease-activated receptors). The predominant thrombin receptor is PAR1, and in endothelial cells (ECs), thrombin dynamically regulates a plethora of phosphorylation events. However, it has remained unclear whether thrombin signaling is exclusively mediated through PAR1. Furthermore, mechanistic insight into activation and inhibition of PAR1-mediated EC signaling is lacking. In addition, signaling networks of biased PAR1 activation after differential cleavage of the PAR1 N terminus have remained an unresolved issue.

Approach and Results—

Here, we used a quantitative phosphoproteomics approach to show that classical and peptide activation of PAR1 induce highly similar signaling, that low thrombin concentrations initiate only limited phosphoregulation, and that the PAR1 inhibitors vorapaxar and parmodulin-2 demonstrate distinct antagonistic properties. Subsequent analysis of the thrombin-regulated phosphosites in the presence of PAR1 inhibitors revealed that biased activation of PAR1 is not solely linked to a specific G-protein downstream of PAR1. In addition, we showed that only the canonical thrombin PAR1 tethered ligand induces extensive early phosphoregulation in ECs.

Conclusions—

Our study provides detailed insight in the signaling mechanisms downstream of PAR1. Our data demonstrate that thrombin-induced EC phosphoregulation is mediated exclusively through PAR1, that thrombin and thrombin–tethered ligand peptide induce similar phosphoregulation, and that only canonical PAR1 cleavage by thrombin generates a tethered ligand that potently induces early signaling. Furthermore, platelet PAR1 inhibitors directly affect EC signaling, indicating that it will be a challenge to design a PAR1 antagonist that will target only those pathways responsible for tissue pathology.
On the Role of Situational Stressors in the Disruption of Global Neural Network Stability during Problem Solving
Authors: Liu Mengting , Amey Rachel C. , Forbes Chad E.
Published: August 2017

When individuals are placed in stressful situations, they are likely to exhibit deficits in cognitive capacity over and above situational demands. Despite this, individuals may still persevere and ultimately succeed in these situations. Little is known, however, about neural network properties that instantiate success or failure in both neutral and stressful situations, particularly with respect to regions integral for problem-solving processes that are necessary for optimal performance on more complex tasks. In this study, we outline how hidden Markov modeling based on multivoxel pattern analysis can be used to quantify unique brain states underlying complex network interactions that yield either successful or unsuccessful problem solving in more neutral or stressful situations. We provide evidence that brain network stability and states underlying synchronous interactions in regions integral for problem-solving processes are key predictors of whether individuals succeed or fail in stressful situations. Findings also suggested that individuals utilize discriminate neural patterns in successfully solving problems in stressful or neutral situations. Findings overall highlight how hidden Markov modeling can provide myriad possibilities for quantifying and better understanding the role of global network interactions in the problem-solving process and how the said interactions predict success or failure in different contexts.
Saccade Reorienting Is Facilitated by Pausing the Oculomotor Program
Authors: Buonocore Antimo , Purokayastha Simran , McIntosh Robert D.
Published: August 2017

As we look around the world, selecting our targets, competing events may occur at other locations. Depending on current goals, the viewer must decide whether to look at new events or to ignore them. Two experimental paradigms formalize these response options: double-step saccades and saccadic inhibition. In the first, the viewer must reorient to a newly appearing target; in the second, they must ignore it. Until now, the relationship between reorienting and inhibition has been unexplored. In three experiments, we found saccadic inhibition ∼100 msec after a new target onset, regardless of the task instruction. Moreover, if this automatic inhibition is boosted by an irrelevant flash, reorienting is facilitated, suggesting that saccadic inhibition plays a crucial role in visual behavior, as a bottom–up brake that buys the time needed for decisional processes to act. Saccadic inhibition may be a ubiquitous pause signal that provides the flexibility for voluntary behavior to emerge.
Restoration of fMRI Decodability Does Not Imply Latent Working Memory States
Authors: Schneegans Sebastian , Bays Paul M.
Published: August 2017

Recent imaging studies have challenged the prevailing view that working memory is mediated by sustained neural activity. Using machine learning methods to reconstruct memory content, these studies found that previously diminished representations can be restored by retrospective cueing or other forms of stimulation. These findings have been interpreted as evidence for an activity-silent working memory state that can be reactivated dependent on task demands. Here, we test the validity of this conclusion by formulating a neural process model of working memory based on sustained activity and using this model to emulate a spatial recall task with retro-cueing. The simulation reproduces both behavioral and fMRI results previously taken as evidence for latent states, in particular the restoration of spatial reconstruction quality following an informative cue. Our results demonstrate that recovery of the decodability of an imaging signal does not provide compelling evidence for an activity-silent working memory state.
On the identity of Acrobeloides longiuterus (Rashid & Heyns, 1990) Siddiqi, De Ley & Khan, 1992 (Rhabditida: Cephalobidae)
Authors: Abolafia Joaquín , Peña-Santiago Reyes
Published: August 2017

Type material of Acrobeloides longiuterus, consisting of three female and six male paratypes, were studied, revealing relevant new data to establish the identity of this species with more accuracy. Its detailed original description is fully confirmed although the ovary is situated in a dextral position with respect to the intestine, a remarkable feature that was not mentioned in the original description, but the same as in A. camberenensis where it was regarded as a diagnostic character. Thus, there is no longer any justification to maintain a separate status for these taxa and A. camberenensis is regarded as a junior synonym of A. longiuterus due to priority of publication.
The D3-D5 region of large subunit ribosomal DNA provides good resolution of German limnic and terrestrial nematode communities
Authors: Schenk Janina , Hohberg Karin , Helder Johannes , Ristau Kai , Traunspurger Walter
Published: August 2017

Reliable and well-developed DNA barcode databases are indispensable for the identification of microscopic life. However, effectiveness of molecular barcoding in identifying terrestrial specimens, and nematodes in particular, has received little attention. In this study,ca600 ribosomal large subunit DNA fragments (D3-D5 region) were successfully amplified for 79 limnic and terrestrial nematode species sampled at 147 locations across Germany. Distinctive DNA motifs in the LSU region were identified in 80% of all species examined. For 13 supposedly single morphospecies, 2-7 LSU barcode groups were detected with a wide range of intraspecific variations (0.09-7.9%). This region seems to be more suitable for the assessment of limno-terrestrial nematode diversity than the frequently used mitochondrial geneCOI, as amplification success of the latter fragment is low for several nematode species. Our reference database for nematodes may serve as a starting point for applied and fundamental studies for these ubiquitous, ecologically highly relevant, organisms.
The Development of Singapore’s Military Justice System
Authors: Goh Joshua Matthew
Published: August 2017

The global trend towards civilianization of military justice systems has had its own unique impact on Singapore’s brand of military justice, in particular its mode of trial by General Court-Martial. This paper explores the development of Singapore’s military justice system since Singapore’s independence, comparing it to developments in the United Kingdom and Canada, two countries that have also civilianized their military justice systems with input from their civil courts, and in the case of the uk, the European Court of Human Rights. These jurisdictions provide a useful comparison on the progress of Singapore’s civilianization reform given both their shared origin of military justice in the English court-martial system and the focus of all three jurisdictions on better protecting the rights of accused servicemen.
The Role of Peacekeeping Operations in International Criminal Justice
Authors: Hamilton Kate
Published: August 2017

International justice is inextricably intertwined with peace. However, where the un Security Council has in the past referred situations to the International Criminal Court it has failed to provide follow-up support. Neither Libya nor Sudan have consented to the icc’s jurisdiction, and without its own police force the icc has faced enormous difficulty in conducting investigations and obtaining the accused. Despite being indicted by the icc, the Libyan authorities are refusing to hand over Saif Al-Islam Gaddafi, whom they have sentenced to death in a domestic trial, and despite repeated calls for his arrest, Sudanese President, Omar Al-Bashir is travelling around the world with impunity. This embarrassing deadlock has led to calls for un troops, already present on the ground in both Libya and Sudan, to intervene. This paper highlights the practical difficulties of such cooperation, looking at case studies of successful cooperation between the icc and peacekeeping missions in the drc, Cote D’Ivoire, and Mali, as well as the role of nato in the former Yugoslavia and contrasting these with the situations in Libya and Sudan. Ultimately, this paper suggests that to extend the mandates of the peacekeeping operations present in Libya and Sudan would compromise the missions, erasing impartiality, leading to a withdrawal of State consent, and requiring such excessive force as to constitute a threat to peace.
Hybrid Regional Order
Authors: Obinna Franklin
Published: August 2017

The un peace operations have undergone significant revisions to calibrate mission mandates in tandem with emerging threats to international peace and security, especially non-traditional security (nts) threats that stem from governance challenges. These multidimensional missions essentially perform statebuilding interventions (sbis) through capacity-building programmes. The future of these missions depends on negotiated political settlements that facilitate the creation of accountable institutions and inclusive societies. Scholars debate the future of un peace missions, especially as it relates to stabilization operations. On the one hand, are the “narrowers” who believe that peace operations should remain focused on stabilizing state authorities. On the other hand, are the “broadeners” who favor people-focused stabilization operations. This article argues for a broad approach. Focusing on the role of regional organizations under Chapter viii of the un Charter, it argues that successive failures by the African Union to implement its doctrinal instruments, particularly the Post Conflict Reconstruction and Development Policy, the African Charter on Democracy, Elections and Governance and the Common African Defence and Security Policy has narrowed its peace interventions in Africa to peace enforcement operations. To be relevant, the African Union needs to focus on the challenges of governance in Africa.
Heterobasidion amyloideopsis sp. nov. (Basidiomycota, Russulales) evidenced by morphological characteristics and phylogenetic analysis
Authors: ZHAO CHANG-LIN , SABA MALKA , KHALID ABDUL NASIR , SONG JIE , PFISTER DONALD H.
Published: August 2017

Heterobasidion amyloideopsis sp. nov., a new poroid wood-inhabiting species from Pakistan, is introduced based on a combination of molecular evidence and morphological characteristics. We generated sequences from the nuclear internal transcribed spacer regions (ITS) and the large subunit ribosomal RNA gene (LSU), the gene encoding the largest subunit of RNA polymerase II (RPB1) and the second subunit of RNA polymerase II (RPB2), focusing on two specimens from Pakistan. We performed phylogenetic analyses with maximum likelihood, maximum parsimony, and bayesian inference methods on two datasets (RPB1+RPB2 and ITS+nLSU+RPB1+RPB2). Both analyses supported the existence of the new species and showed that it formed a monophyletic group within the H. insulare complex as a sister to H. amyloideum. In addition to assessing the origin and divergence of this new species, we focused on the RPB1+RPB2 dataset to perform maximum likelihood based estimation and Bayesian binary analyses. Heterobasidion amyloideopsis is characterized by an annual habit, pileate basidiomata with a rust colored pileal surface, white, obtuse margin, a dimitic hyphal system with simple septate generative hyphae in the trama and clamp connections present on the contextual hyphae, amyloid skeletal hyphae and broadly ellipsoid, hyaline, fairly thick-walled, and asperulate basidiospores.
Notes on the genus Callitriche (Plantaginaceae) in South Africa
Authors: LANSDOWN RICHARD V. , GLEN RENE , HASSEMER GUSTAVO
Published: August 2017

Historically there has been confusion over the status and identification of Callitriche species in South Africa. Review of herbarium specimens and fieldwork have enabled confirmation of the presence of C. deflexa as a naturalised species in this country and confirmed that C. compressa and specimens named as C. bolusii are conspecific. Field surveys showed that C. compressa still occurs in the areas from which most historic collections were made with no evidence of a decline, it is widespread but local in Kwa-Zulu Natal and Eastern Cape Provinces and extends into eastern Western Cape Province. However because it is known from only five widely scattered sites, it is classed as Vulnerable under the IUCN Red List. We also typify here the names C. compressa and C. deflexa.