bluuebunny/crossref_metadata_2025 huggingface dataset:
Pretreatment of Human Platelets with Plasmin Inhibits Responses toThrombin, but Potentiates Responses to Low Concentrations of Aggregating Agents, Including the Thrombin Receptor Activating Peptide, SFLLRN
Authors: Kinlough-Rathbone R L , Perry D W , Rand M L , Packham M A
Published: July 2018

Effects of plasmin on platelets, that influence subsequent responses to aggregating agents, are relevant to attempts to prevent rethrombosis following administration of fibrinolytic agents. We describe plasmin-induced inhibition of platelet responses to thrombin, but potentiation of responses to other aggregating agents. Washed human platelets were labeled with 14C-serotonin, treated for 30 min at 37° C with 0, 0.1 or 0.2 CU/ml of plasmin, followed by aprotinin, washed and resuspended in a Tyrode-albumin solution with apyrase. Incubation with 0.2 CU/ml of plasmin almost completely inhibited thrombin-induced (0.1 U/ml) aggregation, release of 14C-serotonin, and increase in cytosolic [Ca2+]. In contrast, with plasmin-pretreated platelets, aggregation and release of 14C-serotonin were strongly potentiated in response to low concentrations of the thrombin receptor-activating peptide SFLLRN, ADP, platelet-activating factor, collagen, arachidonic acid, the thromboxane mimetic U46619, and the calcium ionophores A23187 and ionomycin. Aspirin or RGDS partially inhibited potentiation. Plasmin-pretreated platelets resuspended in plasma anticoagulated with FPRCH2C1 (PPACK) also showed enhanced responses to aggregating agents other than thrombin. The contrasting effects on responses to thrombin and SFLLRN are noteworthy. Plasmin cleaves GPIIb/IIIa so that it becomes a competent fibrinogen receptor, and binding of 125I-fibrinogen during ADP-induced aggregation was greatly potentiated within 10 s. Potentiation of aggregation by other agonists may be due to increased binding of released fibrinogen. Thus, platelets freed from a thrombus may have increased responsiveness to low concentrations of aggregating agents other than thrombin. These results provide further support for the use of inhibitors of platelet reactions in conjunction with administration of fibrinolytic agents.
Construction and Expression of Mouse-human Chimeric Antibody SZ-51 Specific for Activated Platelet P-selectin
Authors: Gu Jianming , Liu Yue , Xia Lijun , Wan Haiying , Li Peixia , Zhang Xiaomin , Ruan Changgeng
Published: July 2018

A murine monoclonal (mAb) SZ-51 specific for human P-selectin may be used for in vivo thrombus imaging and for the targeting of fibrinolytic agents to thrombi. In order to reduce the immunogenicity of the murine mAb SZ-51 in humans, we cloned and sequenced the cDNAs encoding the variable region of mAb SZ-51 in order to develop mouse/human chimeric reagents. The E. coli expression vector. pHENl-SZ51 Fab/Hu was constructed by fusing the variable regions of mAb SZ-51 with human IgG γICHI and Cκ genes. The constructs were introduced into E. coli HB2151 for expression of soluble chimeric Fab fragment. We also constructed two fusion products by joining the variable regions of mouse antibody to the appropriate constant regions of human Igγl and κ. These chimeras were cloned into two eukaryotic selectable expression vectors separately, which were then cotransfected into a non-Ig secreting murine myeloma line SP2/0 with lipofectin reagent. Six cell lines remained positive for Ig secretion. The highest producing cell line, which showed stable integration and expression at 5 mg/1 of culture, was selected for the large scale production of chimeric antibody. Immunoblotting analysis demonstrated that both of the chimeric antibodies (SZ51Fab/Hu, SZ51/Hu) in the culture supernatants, like the native mAb SZ-51, bind P-selectin. In addition, the whole chimeric antibody can compete for binding to activated platelets with murine SZ-51. Therefore, the SZ-51 chimeric antibody may be a potential agent for diagnosis and treatment of thrombotic diseases in the future.
Prothrombin Fragment F1+2 Is not Predictive for Recurrent Venous Thromboembolism
Authors: Kyrle P A , Eichinger S , Pabinger I , Stümpflen A , Hirschl M , Bialonczyk C , Schneider B , Mannhalter C , Melichart M , Traxler G , Weltermann A , Speiser W , Lechner K
Published: July 2018

It would be important to estimate in advance the risk of recurrent thrombosis. Deficiencies of antithrombin, protein C or protein S, or resistance to activated protein C are associated with a biochemically detectable prethrombotic state. It is thus far unknown whether in patients with a history of thromboembolism but without a defined clotting abnormality a heightened coagulation activation is detectable.

We investigated the value of prothrombin fragment Fl+2 (FI+2) as a predictor of recurrent venous thromboembolism. Furthermore, we compared the Fl+2 levels of thrombosis patients without a defined clotting defect to those of Factor V Leiden patients with a history of venous thrombosis and to those of healthy controls. 180 patients without a defined clotting abnormality and 73 patients with Factor V Leiden were prospectively followed after discontinuation of oral anticoagulants for venous thrombosis and Fl+2 was measured at regular intervals.

Recurrent venous thromboembolism occurred in 23 (9%) of the 253 patients. Before or at several time points after oral anticoagulants, no significant difference in Fl+2 levels was found in patients with and without recurrent thrombosis. Fl+2 levels at 3 weeks and prior to recurrence were not significantly different in both patient groups. Over a one-year observation period, Fl+2 levels of both patients with and without Factor V Leiden were higher than those of the controls. No difference in Fl+2 was seen between patients with and without Factor V Leiden.

We conclude that monitoring of Fl+2 is not suitable for identification of individuals at risk of recurrent venous thrombosis. Permanent hemostatic system activation is detectable both in patients with a defined abnormality of the clotting system and in patients in whom a particular defect has not (yet) been identified.
Hepatitis G Viral RNA in Serum and in Peripheral Blood Mononuclear Cells and Its Relation to HCV-RNA in Patients with Clotting Disorders
Authors: Sheng Li , Soumillion Ann , Peerlinck Kathelijne , Verslype Chris , Lin Lan , Pelt Jos van , Hess Georg , Vermylen Jozef , Yap Sing Hiem
Published: July 2018

The hepatitis G virus (HGV) has recently been identified as a new member of the Flaviviridae family. Infection by this virus is thought to be associated with blood borne hepatitis. In this study, the presence of HCV- and HGV-RNAs in serum or plasma (175 patients) and in peripheral blood mononuclear cells (PBMC) (133 patients) was investigated in patients with clotting disorders using a sensitive reverse transcriptase polymerase chain reaction (RT-PCR). HGV-RNA was detected in serum of 26 patients (14.8%). In apparently healthy blood donors, serum HGV-RNA was detected in 4 of 358 individuals investigated (1.12%). Ninety two percent of the 26 serum HGV-RNA positive patients had coinfection with the hepatitis C virus (HGV), especially with HCV genotype lb, the most common genotype in Belgium. Of these coinfected patients, 15 (62.5%) showed elevated serum ALT levels. Two patients who were solely infected with HGV had normal serum ALT. HGV-RNA in PBMC was found in 18 patients, of whom 3 were negative for serum HGV-RNA. As in case of HCV, HGV-RNA in PBMC is preferentially sensitive to interferon treatment. Nevertheless, rapid reappearance of HGV-RNA in PBMC was observed after cessation of treatment. In one patient, persistent serum ALT elevation seems to be associated with continued HGV viremia, despite the disappearance of serum HCV-RNA.
Platelet Hyporeactivity in Very Low Birth Weight Neonates
Authors: Rajasekhar Damodara , Barnard Marc R , Bednarek Francis J , Michelson Alan D
Published: July 2018

Very few studies have examined platelet function in very low birth weight (VLBW) preterm neonates, because of the relatively large volumes of blood required. In this study, platelet function in clinically stable VLBW neonates was examined by whole blood flow cytometry, which requires only 5 |jl1 of whole blood per assay. The following monoclonal antibodies were used: S12 (P-selectin-specific, reflecting a granule secretion), PAC1 (directed against the fibrinogen binding site exposed on the GPIIb-IIIa complex of activated platelets), F26 (directed against a conformational change in fibrinogen bound to the GPIIb-IIIa complex), and 6D1 (directed against the von Willebrand factor binding site on the GPIb-IX-V complex). VLBW neonates, like normal adults, did not have circulating activated platelets, as determined by the lack of binding of SI2, PAC1, and F26 in the absence of an added agonist. VLBW neonatal platelets were markedly less reactive than adult platelets to thrombin, ADP/epinephrine, and U46619 (a stable thromboxane A2 analogue), as determined by the extent of increase in the platelet binding of SI2, PAC1, and F26, and the extent of decrease in the platelet binding of 6D1. In summary, compared to adults, the platelets of VLBW neonates are markedly hyporeactive to thrombin, ADP/epinephrine and a thromboxane A2 analogue in the physiologic milieu of whole blood, as determined by: 1) the increase in platelet surface P-selectin; 2) the exposure of the fibrinogen binding site on the GPIIb-IIIa complex; 3) fibrinogen binding; and 4) the decrease in platelet surface GPIb. This platelet hyporeactivity may be a factor in the propensity of VLBW neonates to intraventricular hemorrhage. In addition to its previously defined use as a test of platelet hyperreactivity, the present study suggests that whole blood flow cytometry may be useful in the clinical assessment of platelet hyporeactivity.
Performance of Conventional Cytology and Colposcopy for the Diagnosis of Cervical Squamous and Glandular Neoplasias
Authors: Fachetti-Machado Giselle , Figueiredo-Alves Rosane Ribeiro , Moreira Marise Amaral Rebouças
Published: July 2018

Objective To estimate the cytological and colposcopic performances for the diagnosis of cervical neoplasias.

Methods Cross-sectional retrospective study with data from patients' charts. The participants underwent colposcopy, guided biopsies, and excision when needed. The cytological and colposcopic categorization followed the Bethesda System and the international colposcopic terminologies. The cytology and colposcopy performances were evaluated by sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) analyses with 95% confidence interval (95% CI).

Results From 1,571 participants, a total of 1,154 (73.4%) were diagnosed with cervical squamous intraepithelial neoplasia grade 2 or worse (CIN 2+), 114 (7.2%) with adenocarcinoma in situ or worse (AIS+), 615 (39.2%) presented atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion or worse (ASC-H+) cytology, and 934 (59.4%) presented major or suspicious for invasion colposcopic abnormalities. The SE, SP, PPV, and NPV of ASC-H+ for diagnoses of CIN 2+ and AIS+ were, respectively: 44% (95% CI: 41–47) and 72% (95% CI: 67–76), 79% (95% CI: 77–81) and 79% (95% CI: 75–83), 88% (95% CI: 87–90) and 55% (95% CI: 50–60), and 28% (95% CI: 26–31) and 88% (95% CI: 85–91). The SE, SP, PPV, and NPV of major or suspicious for invasion colposcopic abnormalities for diagnoses of CIN 2+ and AIS+ were, respectively: 62% (95% CI: 60–65) and 86% (95% CI: 83–89), 59% (95% CI: 57–62) and 59% (95% CI: 55–64), 85% (95% CI: 83–87) and 44% (95% CI: 40–49), and 29% (95% CI: 27–32) and 92% (95% CI: 89–94).

Conclusion The SE analyses results of ASC-H+ and major or suspicious for invasion colposcopic abnormalities were higher for diagnoses of glandular neoplasias. These results confirm the role of cytology in identifying women at risk who will have their final diagnoses settled by colposcopy and histology.
Application of renormalization group analysis to two-phase turbulent flows with solid dust particles
Authors: Avramenko Andriy A. , Shevchuk Igor V. , Kravchuk Alexander V. , Tyrinov Andrii I. , Shevchuk Vladimir I.
Published: July 2018

Renormalization group methods are used to develop a macroscopic turbulence model for incompressible two phase turbulent flows. The velocity field is divided into slow (large-scale) and fast (small-scale) modes. With the help of the renormalization procedure, momentum equations for the large-scale modes and expressions for effective turbulent viscosity were obtained. These expressions reveal that the presence of the second phase causes decreased turbulent viscosity.
On the edges’ PageRank and line graphs
Authors: Criado Regino , Moral Santiago , Pérez Ángel , Romance Miguel
Published: July 2018

Two different approaches on a directed (and possibly weighted) network G are considered in order to define the PageRank of each edge of G with the focus on its applications. It is shown that both approaches are equivalent, even though it is clear that one approach has clear computational advantages over the other. The usefulness of this concept in the context of applications is illustrated by means of some examples within the area of cybersecurity and some simulations and examples within the scope of subway networks.
Guide star catalog generation for short-wave infrared (SWIR) All-Time star sensor
Authors: Wang Wenjie , Wei Xinguo , Li Jian , Zhang Guangjun
Published: July 2018

As an important part of All-Time star sensor design, the generation of the short-wave infrared (SWIR) guide star catalog is crucial to the system performance. The generation process needs estimation of the instrument magnitude and the guide star selection. Different from the commonly used star sensors, since the SWIR band is far away from the visual band and the detectable magnitude limit of the All-Time star sensor is dynamically changing as the observation conditions vary, the current methods of estimating the instrument magnitude cannot be directly applied and the catalog obtained through the current reduction methods that mainly aimed at improving the distribution uniformity cannot ensure enough stars measured in the field of view under strong sky background radiation. To solve the problems, we propose a method for guide star catalog generation for the All-Time star sensor. First, through the specific analysis of the spectral response curves of the SWIR detector and 2MASS detection bandpasses, the method of estimating instrument magnitudes for the All-Time sensor is determined. Subsequently, dynamic detectable magnitude limits are determined through the signal-to-noise model and the atmospheric background radiation intensity analysis. Based on the dynamic detectable magnitude limits, a reduction method is proposed. The simulation experiment results indicate that the RMS error of the estimation of instrument magnitude is 0.075. Compared to the magnitude filtering method, the guide star catalog obtained through our method can guarantee the completeness, besides, the global distribution uniformity increases by 2.2 times and the local distribution uniformity increases by 10.7 times.
Molecular mechanism of charge inversion revealed by polar orientation of interfacial water molecules: A heterodyne-detected vibrational sum frequency generation study
Authors: Sartin Matthew M. , Sung Woongmo , Nihonyanagi Satoshi , Tahara Tahei
Published: July 2018

“Charge inversion” is a phenomenon in which multivalent counterions overcompensate for interfacial charges and invert the sign of the net charge near a surface. This phenomenon is believed to be relevant to biologically important processes such as DNA condensation, and hence it has attracted much attention. We investigated the polar orientation of interfacial water molecules at two different negatively charged interfaces in the absence and presence of La3+ using heterodyne-detected vibrational sum frequency generation spectroscopy, which can directly determine the up/down orientation of interfacial molecules. It was found that the orientations of water molecules at a bio-relevant phospholipid interface change from the hydrogen-up to the hydrogen-down with the addition of 10 µM La3+. This change of water orientation indicates that the net charge at the phospholipid interface is inverted by adsorption of La3+ to the phosphate headgroup. By contrast, at an alkylsulfate interface, the majority of the interfacial water molecules remain hydrogen-up orientated even in the presence of 25 mM La3+, indicating that the sulfate headgroup is still solvated by up-oriented water. The observed headgroup specificity suggests that charge inversion at the phospholipid interface originates primarily from the chemical interaction between the phosphate and La3+ ion.
Numerical investigations of the effect of rotating and non-rotating shaft on aerodynamic performance of small scale urban vertical axis wind turbines
Authors: Zhang Lidong , Zhu Kaiqi , Jiang Tieliu , Zhang Ling , Li Shaohua , Zhao Xin
Published: July 2018

The shaft is a very important part of small scale vertical axis wind turbines (VAWTs) being used in urban environments. The shedding vortices will be formed as wind passes around the shaft, the shedding vortices released by the shaft have a negative effect on the aerodynamic performance of the blades passing the wake of the wind shaft, and this will lead to lower power output of the wind turbine. The objective of this study is to explore the differences of the effect of the rotating and non-rotating shafts of VAWTs on the aerodynamic performance of small scale urban VAWTs. In addition, the effect of surface roughness on the performance of the rotating and non-rotating shaft wind turbines is also investigated. The dynamic analysis of the VAWT is carried out by the method of Computational Fluid Dynamics. The aerodynamic loads in the study are obtained by solving the two-dimensional (2D) unsteady Navier-Stokes equations with the Transition SST turbulence model. The results are validated with experimental results. The results show that when the ratio of the shaft diameter to the wind turbine diameter (α) is 3.9%, the power coefficient (Cp) of the rotating shaft wind turbine is 2.2% higher than that of the non-rotating shaft wind turbine. Increasing the shaft diameter-based Reynolds number (Res) will increase the Cp of rotating and non-rotating shaft wind turbines, when Res is 2.6 × 104 and the Cp of the non-rotating shaft wind turbine is 5.7% higher than that of the rotating shaft wind turbine. The Cp of the non-rotating and rotating shaft wind turbines is reduced by 6.9% and 6.3%, respectively, by increasing the turbulence intensity from 4% to 16%. The optimal power output occurs under the condition of the non-rotating shaft wind turbine, and the relative surface roughness (ks/ds) is 0.005, where it is observed that Cp increased by 2.1% in comparison to that of the smooth shaft wind turbine.
Bubble dimer dynamics induced by dual laser beam ablation in liquid
Authors: Liu Kai , Chen Jun , Qu Huasong , Dong Yuhang , Gao Yujie , Liu Jiaxin , Liu Xuhai , Zou Yousheng , Zeng Haibo
Published: July 2018

An approach based on dual laser beam ablation in liquid is presented for the preparation of bimetal hydroxide. The dynamics of a dual laser-induced bubble dimer is studied by the combination of an inviscid Rayleigh-Plesset model, an ultrafast camera, and time-resolved shadowgraphy experiments. It indicates that the dual laser-induced bubble pair will rapidly merge into a dimer and then undergo evolution as a single bubble, which can promote the agglomeration of two kinds of metal particles in this thermodynamic environment. Moreover, the atomic ratio of bimetal hydroxide with high crystallinity can be precisely adjusted by the dual laser energy ratio without any additives.
On-chip density mixer enhanced by air chamber
Authors: Takayama Toshio , Miyashiro Hiroki , Tsai Chia-Hung Dylan , Ito Hiroaki , Kaneko Makoto
Published: July 2018

This paper proposes an on-chip density mixer that can achieve even density in a target chamber with a swirling flow enhanced by an air chamber. The system is composed of a main channel, a target chamber where two liquids with different densities are included, an isolated air chamber, and an external vibration pump driven by a piezo actuator at the entrance of the main channel. The air chamber is expected to amplify the vibration owing to structure softening. The amplification would be more pronounced at the resonance frequencies of the structure. We developed the system and conducted experiments. We showed that the swirling motion in the target chamber with an air chamber is stronger than that without an air chamber. We also confirmed that the time resulting in even density is shorter when the pump is driven at a resonance frequency. An air-based virtual valve is introduced for maintaining a constant density in the target chamber.
Hybrid dye-sensitized solar cells with graphene—A convenient method to seal liquid state devices
Authors: Bandara Aruni , Zahra Zahir , Gamage Sachindra , Kumara Ashoka , Perera Ishanie Rangeeka
Published: July 2018

Hybrid dye-sensitized solar cells were fabricated with an iodide/triiodide based liquid electrolyte and graphene as the hole transporting material to overcome the leakage problem associated with liquid state devices. Here, a thin layer of the iodide/triiodide based liquid electrolyte was drop cast onto the working electrode which consists of a dye coated mesoporous TiO2 layer. Then, this thin layer of the liquid electrolyte was sealed with a layer of graphene by the doctor blade method. A platinized transparent conducting oxide glass was used as the counter electrode to complete the device. An overall energy conversion efficiency of 6.13 ± 0.10% with a VOC of 645 ± 20 mV and a JSC of 14.4 ± 1.2 mA cm−2 was observed under AM 1.5 irradiation (1000 W m−2). These devices exhibit a maximum incident photocurrent conversion efficiency of 51.6% which was observed at a wavelength of 525 nm. Furthermore, electrochemical impedance spectroscopy measurements revealed that the charge transfer resistance at the counter electrode/electrolyte interface was significantly reduced compared to the standard iodide/triiodide redox mediator after applying graphene as the hole transporting material which may promote efficient charge transfer within the device.
Characterization of flashover plasma across a large-scale ceramic vacuum interface initiated by explosive electron emission
Authors: Sun Xiao-Liang , Xun Tao , Zhong Hui-Huang , Zhang Jun
Published: July 2018

Flashover plasma characteristics across a large-scale ceramic vacuum interface initiated by explosive electron emission (EEE) are investigated with the experimental and simulation methods. Driven by a negative high voltage pulse (-300 kV, 150 ns), flashover plasma luminescence processes were observed by a high-speed framing camera and the accompanied spectrum characteristics were measured by a spectrograph. Compared with flashover initiated by field electron emission (FEE), a faster light expansion velocity and higher electron temperature of flashover initiated by EEE were obtained which were 200 cm/μs and 4.57 eV, respectively. Radial and angular components characteristics of expansion velocity were analyzed as well and their maximum values were 200 cm/μs and 50 cm/μs. Furthermore, comparisons of flashover initiated by EEE and FEE were conducted by particle-in-cell methods and the results agreed with the experimental observations. From these results it can be concluded that due to higher primary electron energy and stronger secondary electron avalanche and gas ionization, flashover along the ceramic interface initiated by EEE has an easier and faster develop process compared with that initiated by FEE. This work can give a reference for evaluation and design of ceramic vacuum interfaces for high-current applications.
Plasticity based on compensatory effector use in the association but not primary sensorimotor cortex of people born without hands
Authors: Striem-Amit Ella , Vannuscorps Gilles , Caramazza Alfonso
Published: July 2018

Significance

What determines the role of brain regions and their plasticity when typical inputs or experience is not provided? To what extent can extreme compensatory use affect brain organization? We tested the reorganization of primary and association sensorimotor cortex hand-selective areas in people born without hands, who use their feet for everyday tasks. We found that their primary sensorimotor hand area is preferentially activated for nearby body parts that cannot serve as effectors. In contrast, foot-selective compensatory plasticity was found in the association cortex, in an area typically involved in manual tool use. This shows limitations of compensatory plasticity and experience in modifying brain organization of early topographical cortex, as compared with association cortices where function-based organization is the driving factor.
Polymerization pathway of mammalian nonmuscle myosin 2s
Authors: Liu Xiong , Shu Shi , Korn Edward D.
Published: July 2018

Significance

Nonmuscle myosin 2 (NM2) filaments are highly dynamic, polymerizing and depolymerizing in situ at different cellular sites where they are essential for multiple functions including cell division, cell motility, endocytosis, and exocytosis. Therefore, the mechanism of myosin filament assembly and disassembly has high importance. NM2 monomers can be either folded or unfolded. It has been thought that unfolded monomers and antiparallel bipolar dimers are the fundamental polymerization units. We now show that antiparallel, bipolar filaments are formed in vitro by the conversion of folded monomers to folded antiparallel dimers and then antiparallel tetramers that unfold, forming bipolar tetramers. Mature filaments consist of multiple unfolded tetramers with entwined bare zones. These results should assist our understanding of myosin filament dynamics in vivo.
Narrative and persistence
Authors: Olson Eric T. , Witt Karsten
Published: July 2018

Many philosophers say that the nature of personal identity has to do with narratives: the stories we tell about ourselves. While different narrativists address different questions of personal identity, some propose narrativist accounts of personal identity over time. The paper argues that such accounts have troubling consequences about the beginning and end of our lives, lead to inconsistencies, and involve backwards causation. The problems can be solved, but only by modifying the accounts in ways that deprive them of their appeal.
WDR41 supports lysosomal response to changes in amino acid availability
Authors: Amick Joseph , Tharkeshwar Arun Kumar , Amaya, Catherine , Ferguson Shawn M.
Published: July 2018

C9orf72 mutations are a major cause of amyotrophic lateral sclerosis and frontotemporal dementia. The C9orf72 protein undergoes regulated recruitment to lysosomes and has been broadly implicated in control of lysosome homeostasis. However, although evidence strongly supports an important function for C9orf72 at lysosomes, little is known about the lysosome recruitment mechanism. In this study, we identify an essential role for WDR41, a prominent C9orf72 interacting protein, in C9orf72 lysosome recruitment. Analysis of human WDR41 knockout cells revealed that WDR41 is required for localization of the protein complex containing C9orf72 and SMCR8 to lysosomes. Such lysosome localization increases in response to amino acid starvation but is not dependent on either mTORC1 inhibition or autophagy induction. Furthermore, WDR41 itself exhibits a parallel pattern of regulated association with lysosomes. This WDR41-dependent recruitment of C9orf72 to lysosomes is critical for the ability of lysosomes to support mTORC1 signaling as constitutive targeting of C9orf72 to lysosomes relieves the requirement for WDR41 in mTORC1 activation. Collectively, this study reveals an essential role for WDR41 in supporting the regulated binding of C9orf72 to lysosomes and solidifies the requirement for a larger C9orf72 containing protein complex in coordinating lysosomal responses to changes in amino acid availability.
Clustering trees: a visualization for evaluating clusterings at multiple resolutions
Authors: Zappia Luke , Oshlack Alicia
Published: July 2018

Clustering techniques are widely used in the analysis of large datasets to group together samples with similar properties. For example, clustering is often used in the field of single-cell RNA-sequencing in order to identify different cell types present in a tissue sample. There are many algorithms for performing clustering, and the results can vary substantially. In particular, the number of groups present in a dataset is often unknown, and the number of clusters identified by an algorithm can change based on the parameters used. To explore and examine the impact of varying clustering resolution, we present clustering trees. This visualization shows the relationships between clusters at multiple resolutions, allowing researchers to see how samples move as the number of clusters increases. In addition, meta-information can be overlaid on the tree to inform the choice of resolution and guide in identification of clusters. We illustrate the features of clustering trees using a series of simulations as well as two real examples, the classical iris dataset and a complex single-cell RNA-sequencing dataset. Clustering trees can be produced using the clustree R package, available from CRAN and developed on GitHub.
The Perils and Promises of Disability Biography
Authors: Nielsen Kim E.
Published: July 2018

Biographical scholarship provides a means by which to understand the past. Disability biography writes disabled people into historical narratives and cultural discourses, acknowledging power, action, and consequence. Disability biography also analyzes the role of ableism in shaping relationships, systems of power, and societal ideals. When written with skilled storytelling, rigorous study, nuance, and insight, disability biography enriches analyses of people living in the past. Disability biography makes clear the multiple ways by which individuals and communities labor, make kinship, persevere, and both resist and create social change. When using a disability analysis, biographies of disabled people (particularly people famous for their disability, such as Franklin Delano Roosevelt and Helen Keller) reveal the relationality and historically embedded nature of disability. In an ableist world, such acts can be revolutionary.
Disability in Modern Chinese Cinema
Authors: Riep Steven L.
Published: July 2018

Depictions of disability in Chinese-language films from China and Taiwan, once a rarity, have become mainstream since the 1980s and have shifted from critiquing national policies, historical accounts, and collective experiences to highlighting disabled people as complex characters and advocating for greater support for them. These films reveal how disability has become a positive source of identity in its own right. Films from the late 1980s and early 1990s such as Tian Zhuangzhuang’s The Blue Kite use disability to offer critiques of official policies or alternative accounts of historical events. Zhou Sun’s Breaking the Silence and Xue Xiaolu’s Ocean Heaven, which focus on caregiving parents and their disabled children, reveal the need for private, extragovernmental networks of support as well as greater government support for those with disabilities and their families. Finally, films such as Zhang Yimou’s Happy Times feature characters with impairments living rich and rewarding lives, countering stereotypes about disability.
Interpretative Frameworks and the Study of the Rock Arts
Authors: Conkey Margaret W.
Published: July 2018

This chapter explores issues regarding the interpretation of rock art. The chapter considers what interpretation is about, how we define and identify it, and what various ways rock art researchers have engaged with interpretation. Here we mention how they have drawn on concepts of style, structuralism, or shamanism as well as on formal and/or informed methods. There is consideration of the uses of analogy and the direct historical method. Overall, the chapter is framed within the question of what constitutes an ‘authorized’ interpretation and how might we evaluate various interpretations for their validity and insights.
Nightmares and Dreams
Authors: Dodge Jennifer
Published: July 2018

Shale gas development rapidly transformed energy production when new techniques emerged in the late 1990s and 2000s. The combination of high-volume hydraulic fracturing and horizontal drilling, or “fracking,” allowed development in vast, previously inaccessible, “unconventional” oil and gas deposits. Fracking has been welcomed by many national governments as a purportedly low-greenhouse-gas-emitting, energy-security-providing windfall. But it has simultaneously motivated vehement local opposition, to some surprising political effect. Many jurisdictions around the globe now have bans on the practice. This chapter explores shale gas development as a contested “sociotechnical imaginary,” an imagined form of social order reflected in technological projects. Drawing on the controversy in New York in the United States, it demonstrates how the “drill, baby, drill” imaginary was debunked as groups framed it as inherently risky and dangerous, and sought to empower institutions supporting an alternative imaginary.
Oil Opposition
Authors: Stoddart Mark C.J. , Smith Jillian Rene , Graham Paula
Published: July 2018

This chapter examines mobilization against new oil development by Indigenous and environmental activists. Drawing on Canadian examples, two key themes are identified. First, anti-oil activism adopts a diversity of discourses and tactical links between particular oil development projects and broader socio-environmental issues such as colonialism and climate change. Environmental opposition often reflects a conservationist approach that emphasizes ecological risks, which compartmentalizes opposition to specific projects from broader analyses of the oil sector. Indigenous opposition is more often grounded in a rights-based approach that emphasizes Canada’s long history of colonization. Second, where there are alignments between Indigenous and environmental opposition against oil projects, appeals to treaty agreements and environmental justice are used by both indigenous and non-indigenous anti-oil activists to challenge energy projects.
Are We on the Cusp of a Global Renewable Energy Transition?
Authors: Roehrkasten Sybille
Published: July 2018

This chapter examines global energy trends, whether a global renewable energy transition is already taking place, and what steps are needed to further accelerate the global deployment of renewables. It first considers the expansion of renewable energy in light of global energy trends, noting that a global energy transition is not yet a reality but is urgently needed. It then looks at drivers and barriers for an accelerated expansion of renewable energy and proceeds by discussing how renewables are moving from the sidelines to the center stage of global energy governance. In particular, it describes the politics behind the creation of the International Renewable Energy Agency (IRENA), an intergovernmental organization on renewable energy, as well as current challenges for global governance on renewable energy. The chapter shows that global renewable energy capacities have grown significantly but that global energy supply is still dominated by fossil fuels.
Analyzing the Socio-Technical Transformation of Energy Systems
Authors: Rohracher Harald
Published: July 2018

Dealing with the immense societal challenges of climate change and resource depletion requires no less than a fundamental transformation of the energy system, comprising not only technological change, but also cultures of energy use and consumption, new regulations, and new types of actors operating on the energy market. A growing field of interdisciplinary social science research on “sustainability transitions” deals with the dynamics and governance of such transformative, systemic, and socio-technical change processes toward sustainability. This chapter gives an overview of concepts used to study energy system transitions, their strengths and shortcomings, as well as new advancements. The chapter also discusses a concrete example of socio-technical change in the field of renewable energy—wind power—and reflects on some of the lessons that can be drawn from this about the interdependence of energy and society and for an understanding of transitions toward a more sustainable energy system.
A Time of Change, a Time for Change
Authors: Davidson Debra J. , Gross Matthias
Published: July 2018

This chapter discusses prospects for energy-society relations in the twenty-first century, with emphasis on the present challenge: to effect a sociotechnical transition to energy-society relations that are free from greenhouse gas emissions while also minimizing other environmental impacts and ensuring equitable access to energy resources. Three important drivers of this transition are explained: new political realities, new material realities, and new epistemological realities. The chapter considers how the reluctant acceptance by members of the international political elite of the inevitability and severity of the impacts of climate change has altered the politics of energy; how various energy resources exert a physical (and ecological) reality that comes into play in markets, politics, and cultures; and how the genre of energy and society research in the social sciences has evolved over the past century. An overview of the organization of this Handbook is also presented.
Energy Consumption as Part of Social Practices
Authors: Horta Ana
Published: July 2018

This chapter examines social practices as an alternative and promising approach to conventional social science research on energy consumption. It highlights the emergence of practice theory in social science research on energy consumption that focuses on the interaction between social structures and everyday life, including materiality. After providing an overview of the evolution of social science research on energy consumption, the chapter summarizes the “practice turn” in sociology and its extension to research on energy consumption. It then considers the most prominent features of practice theory used in the field of research on energy consumption and concludes by describing the process of formation of the practice of managing the mobile phone as an example of how energy consumption can be analyzed using a practice theory approach.
The International Political Economy of Eastern European Energy Security
Authors: Sharples Jack D.
Published: July 2018

This chapter assesses whether the concerns over regional energy security in Eastern Europe that have arisen since 2013 are caused by market failure, or by commercial gas trade falling victim to regional political tensions, with reference to the trilateral gas relationship between Russia, Ukraine, and the European Union (EU). In doing so, it highlights the political economy of the more competitive, flexible gas market in the EU and the traditional, non-competitive bilateral gas trade between Gazprom (Russia) and Naftogaz (Ukraine) in Eastern Europe, with the latter remaining open to political influence. The chapter concludes that the absence of market mechanisms led to energy security concerns that were later exacerbated by the crisis in political relations between Russia and Ukraine. It follows that the integration of Ukraine into the European gas market and reduction of Russian-Ukrainian bilateral over-dependence, will ease concerns over regional energy security in Eastern Europe.
Theorizing the Behavioral Dimension of Energy Consumption
Authors: Brown Marilyn A. , Sovacool Benjamin K.
Published: July 2018

This chapter focuses on the well-documented misalignment between energy-related behaviors and the personal values of consumers, which has become a major source of angst among policymakers. Despite widespread pro-environmental or green attitudes, consumers frequently purchase non-green alternatives. The chapter identifies 50 theoretical approaches that can be divided almost equally into two types: those that emphasize beliefs, attitudes, and values; and those that also consider contextual factors and social norms. Three principles of intervention are recommended: provide credible and targeted information at points of decision; identify and address the key factors inhibiting and promoting the target behaviors in particular populations; and rigorously evaluate programs to provide credible estimates of impact and opportunities for improvement. The chapter recommends that research on the value-action gap be expanded beyond the traditional focus on individuals to include decision-making units such as households, boards of directors, commercial buying units, and government procurement groups.
Entrainment and Embodiment in Musical Performance
Authors: Montague Eugene
Published: July 2018

This chapter introduces three distinct concepts of entrainment and relates them to the topic of musical embodiment. Drawing on work in music and other disciplines, the chapter discusses the relationships between “long-term,” “short-term,” and “physical” entrainment. Given the close relationship between entrainment and bodily movement, it is argued that each of these concepts implies a particular type of musical body. These types are discussed and compared, and their salient differences identified. The chapter closes with a brief exploration of these three types of entrainment and their related musical bodies, as they can be seen and heard in the course of playing J. S. Bach’s Prelude in C minor, BWV 847.
Music and Psychoanalysis
Authors: Gilman Sander L.
Published: July 2018

When theories of the psyche approach music, the question of the embodiment of music becomes a means of understanding the nature of both music and the psyche. Within psychoanalysis there are three quite different levels of analysis that play a role: the first is therapeutic and asks, “how can we cure aspects of the psyche that have come to make life difficult?” The second looks at the base line of normal human development through an evolutionary model. The third level examines the development of the social structures in which human beings interact as a reflex of their inner lives. It thus examines what Sigmund Freud (1856–1939) labeled “civilization,” a term he made quite fraught in all of its manifestations. Music (and its corollary, listening) functions at all three levels in complex and often contradictory ways in the history of psychoanalysis.
Jesuit Letters
Authors: Nelles Paul
Published: July 2018

This chapter describes the role of letters and written communication in the first decades of the Society of Jesus. Particular attention is given to the work of Juan Alfonso de Polanco, the first permanent Jesuit secretary in Rome and the architect of the Jesuit communications system. The chapter first explores the structural role of the Roman hub, Jesuit record-keeping practices and the creation of the Roman archive, and the place of the college network in Jesuit communications. It then turns to explore the evolution of Jesuit administrative correspondence, edifying letters, and mission letters. Emphasis is placed on the materiality of Jesuit letters and the scale of scribal production in the early Society. Letters were important tools of identity formation and both regulated and mediated Jesuit social activity. In conclusion, the chapter considers how the Jesuit communications network intersected with broader Jesuit knowledge practices.
Central Nervous System Pain Pathways
Authors: Todd Andrew J. , Wang Fan
Published: July 2018

Nociceptive primary afferents detect stimuli that are normally perceived as painful, and these afferents form synapses in the dorsal horn of the spinal cord and the spinal trigeminal nucleus. Here they are involved in highly complex neuronal circuits involving projection neurons belonging to the anterolateral tract (ALT) and interneurons, which modulate the incoming sensory information. The ALT neurons convey somatosensory information to a variety of brain regions that are involved in the various aspects of the pain experience. A spinothalamic-cortical pathway provides input to several regions of the cerebral cortex, including the first and second somatosensory areas (S1, S2), the insula and the cingluate cortex. These regions are thought be responsible for the sensory-discriminative aspects of pain (S1), pain-related learning (S2), the autonomic and motivational responses (insula), and the negative affect (cingulate). Another ascending system, The spinoparabrachial-limbic pathway targets a variety of brain regions, including the amygdala, and is likely involved in the affective component of pain. A descending system that includes the limbic system, the periaqueductal gray matter of the midbrain, the locus coeruleus, and the rostral ventral medulla, can suppress pain, and this operates partly through the monoamine transmitters noradrenaline and serotonin which are released in the spinal and trigeminal dorsal horn.
The Early Heidegger’s Phenomenology
Authors: Dahlstrom Daniel O.
Published: July 2018

This chapter attempts to shed some light on Heidegger’s early conception of phenomenology in light of its conscious departure from Husserl’s conception of phenomenology. The period in question extends from Heidegger’s first Freiburg lectures in 1919 to his return to Freiburg from Marburg in the fall of 1928. After flagging some prima facie differences between their phenomenological projects during these years, this chapter suggests how Heidegger adapts into his phenomenology four basic aspects of Husserl’s phenomenology (the phenomenological reduction, formalization, and the performative and constitutive aspects of the analysis). In conclusion the chapter calls attention to a fundamental, arguably irreconcilable difference between their phenomenologies.
Intentionality
Authors: Moran Dermot
Published: July 2018

This chapter traces the history of intentionality in the phenomenological tradition, from Brentano and Husserl through Heidegger and Merleau-Ponty to Iris Marion Young, emphasizing the continuity and deepening of the concept through the tradition. Brentano’s conceptions of the intentional relation and the intentional inexistence of the object were taken up and transformed in Husserl’s expansive conception of intentionality as the sense-apprehension and sense-making that runs through the whole of experiential and cognitive life. Intentionality, moreover, encompasses not just consciousness’s explicit relation to objects, but also the vaguer awareness of horizons and habitualities (“horizon-intentionality”). Heidegger radicalizes Husserlian intentionality by reframing it in terms of the transcendence of existence. Merleau-Ponty further expands Husserl’s conceptions of embodied and practical intentionality as ambiguous transcendence. Iris Marion Young adds an interesting new dimension through her concept of the socially constituted, inhibited intentionality of women’s bodies.