bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of Virtual Manufacturing Features in forward Manufacturing Process Planning
Authors: Pobozniak Janusz
Published: April 2018

CAPP system is the missing link between CAD/CAM system. Two types of operation of CAPP systems can be distinguished. The first one is the backward process planning, where the part is transformed from its ready state to the stock state. The second method is the forward planning, where the stock is transformed into the finished part. Backward process planning allow for the greater degree of automation, but is difficult for the acceptation among the industrial users. One of the problem in the forward process planning is the necessity to use the manufacturing features which do not occur in the finished part, they occur only in the part intermediate states. The paper propose so called virtual manufacturing features to solve this problem.
Research on Systematic Design and Installation Based on Explosion Protection Technology Combined with Traction Elevator
Authors: Li Changming , Wang Qibing , Leng Yonggang , Li Yu
Published: April 2018

According to GB, NEC, ASME17.1, ANSI A10.4 and EN 81.1 standard, there is a danger of explosive gas or dust. And then for elevator explosion protection, we design a device type up to requirements of NEC Class 1, Division 1, Group C&D as well as NEC Class 1, Division 2. It is also a controllable device type working well in highly explosive and hazardous work areas. We keep the GEDA explosion-proof lift fully fixed to protect workers and materials to the maximum extent. In addition, explosion-proof elevators in China must meet the standards of GB3836.1/2, GB50257, GB7588, etc. Combining the engineering practice over the years, the authors put forward in this paper a method of design and development as well as components based on explosion protection combined with traction elevator, which opens a new window for the systematic design and installation optimization of explosion-proof elevator.
Surface Morphology and Bending Deformation of 2024-T3 Thin Sheets with Laser Peen Forming
Authors: Wu Junfeng , Zou Shikun , Zhang Yongkang , Gong Shuili
Published: April 2018

Laser peen forming (LPF) is a pure mechanical forming method through accumulated plastic strain, which has been successfully applied in wing components. Experimental investigation has been performed to understand the effect of process parameters such as constraint conditions, sheet thickness and laser energy on surface morphology and bending deformation of 2024-T3 thin sheets of dimensions of 76 mm ×19 mm (length × width). The research results indicated that bulges on the aluminum foil were generated at the bottom surface and not generated at the topmost surface. It was different for transition value of two-way bending deformations of thin sheets after LPF with different constraint conditions. Remain flat thicknesses of thin sheets after LPF were about 1 mm ~ 2 mm for 20 J, 25 J and 30 J. Arc heights and curvatures of 3 mm thickness sheets increased with laser energy and those of 2 mm thickness sheets only made little change. It was found that convex deformation, flat, concave deformation and laser deep drawing for thin sheets with different thicknesses after LPF.
Sourire et orthopédie dento-faciale
Authors: Canal Pierre , Galletti Catherine
Published: April 2018

Introduction : La bouche est un élément essentiel du corps humain, c’est par elle que passe le souffle de la vie, la nourriture, etc. enfin elle témoigne de nos émotions. Le sourire est aujourd’hui devenu un moyen important de communication, « d’affirmation » de soi. Objectif : Le premier rôle de l’orthodontiste est de redonner une bonne fonction, mais nos thérapeutiques contribuent à l’évidence à améliorer l’esthétique. Matériels et méthodes : Nous allons, dans cet article et au travers de six cas, montrer que le rétablissement de l’occlusion, de la fonction est le rôle essentiel de l’orthodontie.
Visible-Light-Promoted Difunctionalization of Olefins Leading to α-Thiocyanato Ketones
Authors: Nan Guangming , Yue Huilan
Published: April 2018

A simple and convenient visible-light-induced difunctionalization of alkenes with ammonium thiocyanate and dioxygen has been developed at room temperature. A series of α-thiocyanato ketones could be easily and efficiently obtained in moderate to good yields through the formation of C–S and C=O bonds simply by using nontoxic and inexpensive Na2-Eosin Y as a photocatalyst.
Free Functional Gracilis Muscle Transfer for Reconstruction during Forearm Reimplantation in a Patient with Deep Venous Thrombosis
Authors: Morita Daiki , Nemoto Hitoshi , Miyabe Kenta , Nakae Seiko , Kuroki Tomoaki , Yasuda Tomohiro
Published: April 2018

Background Free muscle transfer is the gold standard procedure for functional upper extremity reconstruction. The gracilis muscle is one of the most commonly used donor muscles due to the reduced morbidity of its harvest.

Case We performed a free gracilis muscle flap transfer for functional reconstruction of a forearm after reimplantation in a 62-year-old man with a known deep venous thrombosis (DVT).

Result Perioperative DVT is a potentially fatal complication due to the risk of pulmonary embolism. There were many risk factors in this case for venous thromboembolism around the time of free flap transfer including the length of the operation, intraoperative position changes, and perioperative suspension of anticoagulants. We divided the operation into two stages to reduce operative times, chose a donor site that did not require intraoperative position changes, placed an indwelling temporary filter in the inferior vena cava preoperatively, and continued administration of anticoagulant intraoperatively.

Conclusion With these measures, we safely and successfully performed free gracilis muscle transfer in a patient with DVT.
Phosphorus oxide gate dielectric for black phosphorus field effect transistors
Authors: Dickerson W. , Tayari V. , Fakih I. , Korinek A. , Caporali M. , Serrano-Ruiz M. , Peruzzini M. , Heun S. , Botton G. A. , Szkopek T.
Published: April 2018

The environmental stability of the layered semiconductor black phosphorus (bP) remains a challenge. Passivation of the bP surface with phosphorus oxide, POx, grown by a reactive ion etch with oxygen plasma is known to improve photoluminescence efficiency of exfoliated bP flakes. We apply phosphorus oxide passivation in the fabrication of bP field effect transistors using a gate stack consisting of a POx layer grown by reactive ion etching followed by atomic layer deposition of Al2O3. We observe room temperature top-gate mobilities of 115 cm2 V−1 s−1 in ambient conditions, which we attribute to the low defect density of the bP/POx interface.
Adaptive logical stochastic resonance in time-delayed synthetic genetic networks
Authors: Zhang Lei , Zheng Wenbin , Song Aiguo
Published: April 2018

In the paper, the concept of logical stochastic resonance is applied to implement logic operation and latch operation in time-delayed synthetic genetic networks derived from a bacteriophage λ. Clear logic operation and latch operation can be obtained when the network is tuned by modulated periodic force and time-delay. In contrast with the previous synthetic genetic networks based on logical stochastic resonance, the proposed system has two advantages. On one hand, adding modulated periodic force to the background noise can increase the length of the optimal noise plateau of obtaining desired logic response and make the system adapt to varying noise intensity. On the other hand, tuning time-delay can extend the optimal noise plateau to larger range. The result provides possible help for designing new genetic regulatory networks paradigm based on logical stochastic resonance.
The influence of titanium adhesion layer oxygen stoichiometry on thermal boundary conductance at gold contacts
Authors: Olson David H. , Freedy Keren M. , McDonnell Stephen J. , Hopkins Patrick E.
Published: April 2018

We experimentally demonstrate the role of oxygen stoichiometry on the thermal boundary conductance across Au/TiOx/substrate interfaces. By evaporating two different sets of Au/TiOx/substrate samples under both high vacuum and ultrahigh vacuum conditions, we vary the oxygen composition in the TiOx layer from 0 ≤ x ≤ 2.85. We measure the thermal boundary conductance across the Au/TiOx/substrate interfaces with time-domain thermoreflectance and characterize the interfacial chemistry with x-ray photoemission spectroscopy. Under high vacuum conditions, we speculate that the environment provides a sufficient flux of oxidizing species to the sample surface such that one essentially co-deposits Ti and these oxidizing species. We show that slower deposition rates correspond to a higher oxygen content in the TiOx layer, which results in a lower thermal boundary conductance across the Au/TiOx/substrate interfacial region. Under the ultrahigh vacuum evaporation conditions, pure metallic Ti is deposited on the substrate surface. In the case of quartz substrates, the metallic Ti reacts with the substrate and getters oxygen, leading to a TiOx layer. Our results suggest that Ti layers with relatively low oxygen compositions are best suited to maximize the thermal boundary conductance.
Decoding the spectroscopic features and time scales of aqueous proton defects
Authors: Napoli Joseph A. , Marsalek Ondrej , Markland Thomas E.
Published: April 2018

Acid solutions exhibit a variety of complex structural and dynamical features arising from the presence of multiple interacting reactive proton defects and counterions. However, disentangling the transient structural motifs of proton defects in the water hydrogen bond network and the mechanisms for their interconversion remains a formidable challenge. Here, we use simulations treating the quantum nature of both the electrons and nuclei to show how the experimentally observed spectroscopic features and relaxation time scales can be elucidated using a physically transparent coordinate that encodes the overall asymmetry of the solvation environment of the proton defect. We demonstrate that this coordinate can be used both to discriminate the extremities of the features observed in the linear vibrational spectrum and to explain the molecular motions that give rise to the interconversion time scales observed in recent nonlinear experiments. This analysis provides a unified condensed-phase picture of the proton structure and dynamics that, at its extrema, encompasses proton sharing and spectroscopic features resembling the limiting Eigen [H3O(H2O)3]+ and Zundel [H(H2O)2]+ gas-phase structures, while also describing the rich variety of interconverting environments in the liquid phase.
Squeeze-film flow between a flat impermeable bearing and an anisotropic porous bed
Authors: Karmakar Timir , Raja Sekhar G. P.
Published: April 2018

We consider a theoretical model of the squeeze film in the presence of a porous bed. The gap between the porous bed and the bearing is assumed to be filled with a Newtonian fluid. We use the Navier-Stokes equation in the fluid region and the Darcy equation in the fluid filled porous region. Lubrication approximation is used to derive the corresponding evolution equation for the film thickness. We use G. S. Beavers and D. D. Joseph [“Boundary conditions at a naturally permeable wall,” J. Fluid. Mech. 30, 197–207 (1967)] and M. Le Bars and M. G. Worster [“Interfacial conditions between a pure fluid and a porous medium: Implications for binary alloy solidification,” J. Fluid. Mech. 550, 149–173 (2006)] condition at the liquid porous interface and present a detailed analysis on the corresponding impact. We assume that the porous bed is anisotropic in nature with permeabilities K2 and K1 along the principal axes. Accordingly, the anisotropic angle ϕ is taken as the angle between the horizontal direction and principal axis with permeability K2. We show that the anisotropic permeability ratio and the anisotropic angle make a significant influence on the contact time, flux, velocity, etc. Contact time to meet the porous bed when a bearing approaches under a constant prescribed load is estimated. We present some important findings (relevant to the knee joint) based on the anisotropic properties of the human cartilage. For a prescribed constant load, we have estimated the time duration, during which a healthy human knee remains fluid lubricated.
Another look at zonal flows: Resonance, shearing, and frictionless saturation
Authors: Li J. C. , Diamond P. H.
Published: April 2018

We show that shear is not the exclusive parameter that represents all aspects of flow structure effects on turbulence. Rather, wave-flow resonance enters turbulence regulation, both linearly and nonlinearly. Resonance suppresses the linear instability by wave absorption. Flow shear can weaken the resonance, and thus destabilize drift waves, in contrast to the near-universal conventional shear suppression paradigm. Furthermore, consideration of wave-flow resonance resolves the long-standing problem of how zonal flows (ZFs) saturate in the limit of weak or zero frictional drag, and also determines the ZF scale. We show that resonant vorticity mixing, which conserves potential enstrophy, enables ZF saturation in the absence of drag, and so is effective at regulating the Dimits up-shift regime. Vorticity mixing is incorporated as a nonlinear, self-regulation effect in an extended 0D predator-prey model of drift-ZF turbulence. This analysis determines the saturated ZF shear and shows that the mesoscopic ZF width scales as LZF∼f3/16(1−f)1/8ρs5/8l03/8 in the (relevant) adiabatic limit (i.e., τckk‖2D‖≫1). f is the fraction of turbulence energy coupled to ZF and l0 is the base state mixing length, absent ZF shears. We calculate and compare the stationary flow and turbulence level in frictionless, weakly frictional, and strongly frictional regimes. In the frictionless limit, the results differ significantly from conventionally quoted scalings derived for frictional regimes. To leading order, the flow is independent of turbulence intensity. The turbulence level scales as E∼(γL/εc)2, which indicates the extent of the “near-marginal” regime to be γL<εc, for the case of avalanche-induced profile variability. Here, εc is the rate of dissipation of potential enstrophy and γL is the characteristic linear growth rate of fluctuations. The implications for dynamics near marginality of the strong scaling of saturated E with γL are discussed.
Where wildfires destroy buildings in the US relative to the wildland–urban interface and national fire outreach programs
Authors: Kramer H. Anu , Mockrin Miranda H. , Alexandre Patricia M. , Stewart Susan I. , Radeloff Volker C.
Published: April 2018

Over the past 30 years, the cost of wildfire suppression and homes lost to wildfire in the US have increased dramatically, driven in part by the expansion of the wildland–urban interface (WUI), where buildings and wildland vegetation meet. In response, the wildfire management community has devoted substantial effort to better understand where buildings and vegetation co-occur, and to establish outreach programs to reduce wildfire damage to homes. However, the extent to which the location of buildings affected by wildfire overlaps the WUI, and where and when outreach programs are established relative to wildfire, is unclear. We found that most threatened and destroyed buildings in the conterminous US were within the WUI (59 and 69% respectively), but this varied considerably among states. Buildings closest to existing Firewise communities sustained lower rates of destruction than further distances. Fires with the greatest building loss were close to outreach programs, but the nearest Firewise community was established after wildfires had occurred for 76% of destroyed buildings. In these locations, and areas new to the WUI or where the fire regime is predicted to change, pre-emptive outreach could improve the likelihood of building survival and reduce the human and financial costs of structure loss.
Descending pathway facilitates undulatory wave propagation in
Caenorhabditis elegans
through gap junctions
Authors: Xu Tianqi , Huo Jing , Shao Shuai , Po Michelle , Kawano Taizo , Lu Yangning , Wu Min , Zhen Mei , Wen Quan
Published: April 2018

Significance

A deep understanding of the neural basis of motor behaviors must integrate neuromuscular dynamics, mechanosensory feedback, as well as global command signals, to predict behavioral dynamics. Here, we report on an integrative approach to define the circuit logic underlying locomotion in
Caenorhabditis elegans
. Our combined experimental and computational analyses revealed that (
i
) motor neurons in
C. elegans
function as oscillators; (
ii
) descending interneuron inputs and proprioceptive coupling between motor neurons work synergistically to facilitate the sequential activation of motor neuron activities, allowing bending waves to propagate efficiently along the body. Our work represents a key step toward an integrative view of animal locomotion.
Social contagion of ethnic hostility
Authors: Bauer Michal , Cahlíková Jana , Chytilová Julie , Želinský Tomáš
Published: April 2018

Significance

We provide experimental evidence on peer effects and show that behavior that harms members of a different ethnic group is twice as contagious as behavior that harms coethnics. The findings may help to explain why ethnic hostilities can spread quickly (even in societies with few visible signs of interethnic hatred) and why many countries have adopted hate crime laws, and illustrate the need to study not only the existence of discrimination, but also the stability of attitudes and behaviors toward outgroup members.
Synaptic adhesion protein ELFN1 is a selective allosteric modulator of group III metabotropic glutamate receptors
in trans
Authors: Dunn Henry A. , Patil Dipak N. , Cao Yan , Orlandi Cesare , Martemyanov Kirill A.
Published: April 2018

Significance

G protein-coupled receptors (GPCRs) continue to be the pharmaceutical target of over one-third of FDA-approved drugs, yet our understanding of GPCR function has been overwhelmingly limited to the study of intracellular effectors. It is emerging that GPCRs also associate with a variety of extracellular proteins, yet the functional consequences of these interactions have been ill defined for the lack of robust approaches to measure them. In this study, we develop a unique assay platform and provide an example of transcellular modulation of GPCR properties by association with a synaptic adhesion molecule.
One prophage WO gene rescues cytoplasmic incompatibility in
Drosophila melanogaster
Authors: Shropshire J. Dylan , On Jungmin , Layton Emily M. , Zhou Helen , Bordenstein Seth R.
Published: April 2018

Significance

The World Health Organization recommended pilot deployment of
Wolbachia
-infected mosquitoes to curb viral transmission to humans. Releases of mosquitoes are underway worldwide because
Wolbachia
can block replication of these pathogenic viruses and deterministically spread by a drive system termed cytoplasmic incompatibility (CI). Despite extensive research, the underlying genetic basis of CI remains only half-solved. We recently reported that two prophage WO genes recapitulate the modification component of CI in a released strain for vector control. Here we show that one of these genes underpins rescue of CI. Together, our results reveal the complete genetic basis of this selfish trait and pave the way for future studies exploring WO prophage genes as adjuncts or alternatives to current control efforts.
Suppressing viscous fingering in structured porous media
Authors: Rabbani Harris Sajjad , Or Dani , Liu Ying , Lai Ching-Yao , Lu Nancy B. , Datta Sujit S. , Stone Howard A. , Shokri Nima
Published: April 2018

Significance

Viscous fingering commonly takes place during injection of one fluid that displaces a resident fluid in a porous medium. Fingering normally is promoted where the injected fluid is less viscous than the resident fluid being displaced. We propose a design of a porous medium in the form of an ordered structure to suppress or trigger (depending on the application) viscous fingering in porous media without modifying fluid properties or wettability. We utilize pore-scale direct numerical simulations, state-of-art experiments and analysis to derive predictive tools to evaluate effects of various parameters on controlling viscous fingering in porous media. Moreover, we propose generalized analytical solutions and a phase diagram for the parameter space affecting viscous fingering patterns.
Embryonic regeneration by relocalization of the Spemann organizer during twinning in
Xenopus
Authors: Moriyama Yuki , De Robertis Edward M.
Published: April 2018

Significance

Many animals, including humans, can generate identical twins from a single egg. We perfected a method by which a frog (
Xenopus
) egg cut in half along the dorsal–ventral (back to belly) axis at the 4,000-cell stage produced twins at high frequency. The large wound generated by bisection healed within an hour, juxtaposing cells that would normally form the most dorsal and ventral tissues in the intact embryo. Tracing the fate of microinjected cells showed that the dorsal Spemann organizer was formed 90° away from its original location in bisected embryos. A new gradient of dorsal–ventral signaling was generated by this displacement, explaining the regeneration of the missing half. The experiments help explain twinning in a classic model system.
Operationalising social investment: from policy dimensions to ideal-types
Authors: Andersson Lisa
Published: April 2018

Social investment in Europe has primarily been measured by studying expenditure data from specific categories of social policy. This article argues that we need a more nuanced way of studying the presence of social investment, and develops a tool for measuring the ideational content of social investment in policy regulations. By operationalising three key policy dimensions of social investment; time, distribution and policy coherence, varying approaches of social investment are discerned, landing in the development of three ideal types: a strict social investment, a targeted social investment and a reactive social investment. To demonstrate its application, the social investment ideal-types are applied to cases of policies for unemployed youth in different European countries. The operationalisation and ideal types presented in this article provide a structure and nuance to the understanding and measuring of social investment, aiding in the further debate on its pros, cons and presence in European social policy.
Dual therapy for Aβ amyloidosis in AD: A successful one-two combo
Authors: Patel Tirth K. , Holtzman David M.
Published: April 2018

In this issue, Chiang et al. (https://doi.org/10.1084/jem.20171484) make a notable contribution to Alzheimer disease (AD) therapeutics in a thorough and rigorous study demonstrating superior efficacy of dual therapy against Aβ in a mouse model of amyloid β deposition.
Outcomes of Anesthesia Selection in Endovascular Treatment of Acute Ischemic Stroke
Authors: Peng Yuming , Wu Youxuan , Huo Xiaochuan , Wu Peng , Zhou Yang , Li Jiaxin , Liang Fa , Liu Xiaoyuan , Pan Yuesong , Miao Zhongrong , Han Ruquan
Published: April 2018

Background:

The association between anesthesia type and outcomes in patients with acute ischemic stroke undergoing endovascular treatment (EVT) remains a subject of ongoing debate.

Methods:

This prospective nonrandomized controlled trial included 149 consecutive patients with acute anterior circulation stroke who underwent EVT. The primary outcome was functional independence assessed by the modified Rankin Scale (mRS) after 3 months.

Results:

A total of 105 (70.5%) and 44 (29.5%) patients undergoing EVT who received conscious sedation (CS) and general anesthesia (GA), respectively. The patients who received GA had similar demographics and basic National Institute of Health Stroke Scale scores (17 vs. 16, P>0.05) as the patients who received CS. The recanalization time (304 vs. 311 min, P=0.940) and the recanalization rate (86.4% vs. 84.1%, P=0.170) did not differ between the patients receiving the different types of anesthesia. The National Institute of Health Stroke Scale at 24 hours was lower in the patients who received CS than in those who received GA (β=−2.26, 95% confidence interval, −5.30 to 0.79). The independence (modified Rankin Scale score 0 to 2) at 3 months was equal between patients who received GA and those who received CS (odds ratio=0.73, 95% confidence interval, 0.32-1.68). The mortality and the morbidity rates did not differ.

Conclusions:

The data indicated that the selection of GA or CS during EVT had no impact on the independent outcomes of patients with anterior circulation occlusion.
Clinical Results of Lateral Extra-Articular Tenodesis
Authors: Batty Lachlan , Lording Timothy
Published: April 2018

In the anterior cruciate ligament (ACL) deficient knee, excellent outcomes are achieved in many patients with an isolated, intra-articular ACL reconstruction. Some patients, however, have ongoing instability or suffer graft rupture. Failure after ACL reconstruction is multifactorial, but residual anterolateral rotatory laxity is 1 potential contributing factor. Lateral extra-articular procedures are a heterogenous group of operations that were initially described as isolated treatments for the ACL deficient knee, and subsequently used in combination with intra-articular reconstructions. Initial observational studies were encouraging, however, comparative studies were less flattering and lead to a general abandonment of these procedures. With improved understanding of the anatomy and biomechanics of the anterolateral capsuloligamentous complex there has been a renewed interest in these procedures. Recent systematic reviews suggest efficacy of these procedures in improving rotational control, though data showing improved patient reported outcomes or reduced graft rupture rates are lacking. Preliminary results from ongoing clinical trials are supportive for lateral extra-articular tenodesis when used as an augment to modern, intra-articular ACL reconstructions in targeted, high-risk patients.
Correlation with lymphocyte infiltration, but lack of prognostic significance of MECA-79-positive high endothelial venules in primary malignant melanoma
Authors: Sebestyén Tímea , Mohos Anita , Liszkay Gabriella , Somlai Beáta , Gaudi István , Ladányi Andrea
Published: April 2018

High endothelial venules (HEVs) are specialized vessels in lymphoid organs, supporting lymphocyte trafficking from the blood. As the presence of these vessels was described recently in tumors, it was proposed that they could facilitate the development of antitumor immune response, resulting in improved prognosis. The aim of our study was to analyze the correlation of the density of HEVs with that of the different immune cell types as well as with the clinicopathologic parameters and the disease outcomes in patients with cutaneous melanoma. Primary melanoma samples of 118 patients were analyzed retrospectively by immunohistochemical labeling and quantitation of vessels stained with the MECA-79 antibody, as well as a panel of eight different immune cell types (CD8+ and CD45RO+ T cells, lymphocytes expressing the CD25, CD134, or CD137 activation markers, FOXP3+ regulatory T cells, CD20+ B cells, and DC-LAMP+ mature dendritic cells). Correlations of MECA-79+ vessel density with that of the immune cells, as well as with clinicopathologic parameters and disease outcomes were evaluated. We showed that the number of MECA-79+ vessels correlates strongly with the peritumoral density of B and T lymphocytes. Moreover, higher HEV numbers were detected in tumors hosting tertiary lymphoid structures as well as in those of axial location compared with the ones in the extremity and in men compared with women, whereas no association was found with patient age, tumor thickness, histologic type or ulceration, or with the survival of melanoma patients. The density of MECA-79+ HEVs in primary melanomas shows a correlation with B and T-lymphocyte density and differences according to the presence of tertiary lymphoid structures, tumor site, and the sex of the patient. However, it has no prognostic value.
Role of D1-like and D2-like dopamine receptors within the ventral tegmental area in stress-induced and drug priming-induced reinstatement of morphine seeking in rats
Authors: Farahimanesh Sharareh , Moradi Marzieh , Nazari-Serenjeh Farzaneh , Zarrabian Shahram , Haghparast Abbas
Published: April 2018

The ventral tegmental area (VTA) as a major source of dopamine neurons projecting to cortical and limbic regions has a crucial role in reward as well as stress processes. Dopamine is a predominant neurotransmitter in the reward system, which plays an important role in both drug priming-induced and cue-induced reinstatement of cocaine and heroin seeking. It has been shown that this neurotransmitter has a role in stress-induced relapse to drug seeking. Therefore, the present study aims to evaluate the effects of intra-VTA administration of SCH-23390, as a dopamine D1-like receptor antagonist, and sulpiride, as a dopamine D2-like receptor antagonist, on drug priming-induced and food deprivation (FD)-induced reinstatement. The rats were bilaterally implanted by two separate cannulae into the VTA. After the acquisition and extinction of morphine-conditioned place preference, the animals received different doses of SCH-23390 or sulpiride (0.15, 0.4, 1.5 and 4 mg/0.3 µl vehicle per side) into the VTA on the reinstatement day and tested for drug priming-induced reinstatement of morphine (1 mg/kg) or FD-induced reinstatement facilitated by an ineffective dose of morphine (0.5 mg/kg) in separate groups. Our findings indicated that the D1/D2-like receptor antagonists attenuated the drug priming-induced and FD-induced reinstatement. However, these decrements were more significant in groups of animals that received a 24-h FD as a stressor. The data may suggest a role for the VTA dopaminergic system in relapse to drugs of abuse, which may be induced either by re-exposure to morphine or exposure to a stressor.
Voriconazole Treatment for an Infant With Intractable Candida glabrata Meningitis
Authors: Tsakiri Sophia , Aneji Chiamaka , Domonoske Christine , Mazur Lynnette , Benjamin Daniel K. , Wootton Susan H.
Published: April 2018

We report voriconazole levels in an infant with disseminated Candida glabrata infection who received combination antifungal therapy and rescue voriconazole treatment. Serum and cerebrospinal fluid voriconazole levels were higher than anticipated and above target. Dose reduction did not lead to a reduction in the blood or cerebrospinal fluid levels. The patient did not exhibit identifiable drug toxicity.
Hematologic Adverse Events Associated With Prolonged Valganciclovir Treatment in Congenital Cytomegalovirus Infection
Authors: Ziv Liron , Yacobovich Joanne , Pardo Joseph , Yarden-Bilavsky Havatzelet , Amir Jacob , Osovsky Micky , Bilavsky Efraim
Published: April 2018

Background:

Valganciclovir (2/d) therapy for 6 months in neonates with symptomatic congenital cytomegalovirus (cCMV) infection improves hearing and neurodevelopmental outcome. The only reported adverse event was neutropenia. Since 2009, our protocol for symptomatic cCMV infection was a 1-year treatment of 2/d for the first 3 months followed by 9 months of 1/d.

Methods:

A retrospective study. Infants with cCMV treated with valganciclovir for 1 year were recruited. Data of drug-related hematologic adverse events were collected.

Results:

One hundred sixty infants were eligible; 46 (28.8%) had experienced at least 1 episode of neutropenia (58 episodes), the majority (39/46, 84.8%) during the first 3 months of treatment and 7 (15.2%) during the last 9 months of treatment. Grades 3 and 4 neutropenia occurred in 9 (5.6%) children, almost exclusively during the first 3 months of treatment. Anemia (hemoglobin <9 g/dL) was recorded in 12 (7.5%) children during the first 3 months of 2/d treatment. Four children presented with hemoglobin levels <7 g/dL and needed a blood transfusion. One child was diagnosed with transient pure red cell aplasia. No long-term adverse events were recorded.

Conclusions:

Although prolonged valganciclovir treatment for cCMV is safe, a close monitoring of the white blood cell count and hemoglobin levels is warranted. Much lower rates of grades 3 and 4 neutropenia were observed than previously reported, probably owing to our unique treatment protocol. Nevertheless, drug-induced anemia should be of primary concern. The optimal protocol assessing clinical outcome, concurrently with potential side effects, has not yet been determined.
Activating P2X7 Receptors Increases Proliferation of Human Pancreatic Cancer Cells via ERK1/2 and JNK
Authors: Choi Ji Hun , Ji Young Geon , Ko Jung Jae , Cho Han Jun , Lee Dong Hyeon
Published: April 2018

Objectives

The aim of this study was to investigate the effects of the activated P2X7 receptors on the proliferation and growth of human pancreatic cancer cells.

Methods

Proliferation was measured by incorporating bromodeoxyuridine into pancreatic cancer cells, MIA PaCa-2 and HPAC. Expression of P2 receptors and signal molecules was examined using quantitative reverse transcription/polymerase chain reaction and/or Western blot. Proliferative effects of the P2X7 receptors in vivo were examined using a xenotransplant model of pancreatic cancer cell lines.

Results

Incubating pancreatic cancer cells with adenosine triphosphate (ATP) and 2′(3′)-O-(4-Benzoylbenzoyl)ATP resulted in a dose-dependent increase of cell proliferation. The P2 receptor antagonist, KN-62, and small interfering RNA against P2X7 receptors, significantly decreased the proliferative effects of ATP. The ATP-induced proliferation was mediated by protein kinase C, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK); specifically, ATP increased the phosphorylation of ERK1/2 and JNK. The expression of inducible nitric oxide synthase was decreased by P2X7 receptor activation. In a xenotransplant model, applying ATP significantly increased the growth of induced tumors.

Conclusions

The P2X7 receptor activation by extracellular nucleotides increased proliferation and growth of human pancreatic cancer cells via ERK1/2 and JNK. This supports the pathophysiological role of P2X7 receptors in pancreatic disease and recovery.
Functional Somatic Symptoms Across Cultures: Perceptual and Health Care Issues
Authors: Löwe Bernd , Gerloff Christian
Published: April 2018

Functional neurological disorders are conceptualized as patterns of neurological symptoms that cannot be attributed to a clear organic etiology. The study by Wilkins et al. in this issue of Psychosomatic Medicine reveals that 8.2% of patients who were initially presented with suspected stroke were later diagnosed with functional disorders, i.e., “functional stroke mimics.” However, the percentage of functional stroke mimics varied substantially with patients' nationality, age, and sex. In this editorial comment, we discuss potential reasons for the intercultural variation of the frequency of functional stroke mimics.

The current models of symptom perception, in which symptom perception is guided by top-down processes of the central nervous system, are helpful in explaining the intercultural variation of functional symptoms. According to these models, cultural beliefs, previous illnesses, and stressful life situations influence patients' expectations, sensory input, and finally the perception of somatic symptoms. In addition, differences in insurance status, health literacy, and health care experiences are strong predictors of health care use in patients who experience somatic symptoms.

This article provides a conceptual model that integrates sociocultural factors with symptom perception and health care use relevant to the different rates of functional somatic symptoms in emergency departments across nationalities. Considering these factors, future attempts to improve care for patients with functional disorders should enhance access to effective treatment for all patient groups, empower patients through education and early participation in the treatment process, and foster interdisciplinary collaboration among specialists from somatic and mental health disciplines.
Biliary Drainage in Patients With Failed ERCP: Percutaneous Versus EUS-guided Drainage
Authors: Téllez-Ávila Félix I. , Herrera-Mora David , Duarte-Medrano Gilberto , Lopez-Arce Gustavo , Lindoro-Barraza Dayana , Casanova Iván , Elizondo-Rivera Javier , Ramírez-Luna Miguel , Valdovinos-Andraca Francisco
Published: April 2018

Aim:

The goal of the study is to compare the efficacy and safety of bile duct drains guided by endoscopic ultrasound-guided biliary drainage (EGBD) versus percutaneous transhepatic biliary drainage (PTBD).

Materials and Methods:

Retrospective comparative study. Patients with obstruction of the bile duct who underwent the EGBD or PTBD procedure and had at least 1 previous endoscopic retrograde cholangiopancreatography that failed or was inaccessible to the second duodenal portion were included.

Results:

A total of 90 patients were initially evaluated and 28 were excluded. There were 39 (62.9%) women, with a median age of 55.6 years (range, 22 to 88 y). The etiology of biliary obstruction was malignancy in 35 (56.4%) patients. Differences between EGBD versus PTBD groups were in technical success (90% vs. 78%; P=0.3), clinical success (96% vs. 63%; P=0.04), complications (6.6% vs. 28%; P=0.04), length of stay [6.5 d (range, 0 to 11 d) vs. 12.5 d (range, 6.2 to 25 d)] (P=0.009), and costs 1440.15±240.94 versus 2165.87±241.10 USD (P=0.03).

Conclusions:

EGBD is associated with a higher clinical success rate and safety, shorter hospital stays, and lower cost compared with PTBD.
Constructing and Navigating Cultural Borderlands Using Augmentative and Alternative Communication
Authors: Smith Martine M.
Published: April 2018

Individuals who use augmentative and alternative communication (AAC) occupy complex sociocultural and sociolinguistic territories. They are immersed in spoken language communities but to participate as speakers in conversational interactions, they may rely on atypical communication modes, including systems for generating speech that set them apart as what Mattingly (2006) termed “Other.” This article explores the challenges and tensions implicit in shifting between cultural roles of Natural Speaker and Aided Communicator using the construct of cultural borderlands. Borderlands are first explored in terms of social participation, focusing on questions such as whether aided communication offers a bridge across borderlands or constitutes a marker of cultural difference and on the question of ownership of aided communication. The borderlands of speaker–listener roles that are negotiated within interactions involving aided communication are then considered. Possible implications of how the construct of cultural borderlands supports understanding of interactions involving aided communication are suggested.
Investigating the combined association of BMI and alcohol consumption on liver disease and biomarkers: a Mendelian randomization study of over 90 000 adults from the Copenhagen General Population Study
Authors: Carter Alice R , Borges Maria-Carolina , Benn Marianne , Tybjærg-Hansen Anne , Smith George Davey , Nordestgaard Børge G , Lawlor Debbie A
Published: April 2018

Background

Body mass index (BMI) and alcohol consumption are suggested to independently and interactively increase the risk of liver disease. We assessed this combined effect using factorial Mendelian randomization (MR).

Methods

We used multivariable adjusted regression and MR to estimate individual and joint associations of BMI and alcohol consumption and liver disease biomarkers (alanine aminotransferase (ALT) y-glutamyltransferase (GGT)) and incident liver disease. We undertook a factorial MR study splitting participants by median of measured BMI or BMI allele score then by median of reported alcohol consumption or ADH1B genotype (AA/AG and GG), giving four groups; low BMI/low alcohol (-BMI/-alc), low BMI/high alcohol (-BMI/+alc), high BMI/low alcohol (+BMI/-alc) and high BMI/high alcohol (+BMI/+alc).

Results

Individual positive associations of BMI and alcohol with ALT, GGT and incident liver disease were found. In the factorial MR analyses, considering the +BMI/+alc group as the reference, mean circulating ALT and GGT levels were lowest in the -BMI/-alc group (2.32% (95% CI: −4.29, −0.35) and −3.56% (95% CI: −5.88; −1.24) for ALT and GGT respectively). Individuals with -BMI/+alc and +BMI/-alc had lower mean circulating ALT and GGT compared to the reference group (+BMI/+alc). For incident liver disease multivariable factorial analyses followed a similar pattern to those seen for the biomarkers, but little evidence of differences between MR factorial categories for odds of liver disease.

Conclusions

Consistent results from multivariable regression and MR analysis, provides compelling evidence for the individual adverse effects of BMI and alcohol consumption on liver disease. Intervening on both BMI and alcohol may improve the profiles of circulating liver biomarkers. However, this may not reduce clinical liver disease risk.
In silicoanalysis of piRNAs in retina reveals potential targets in intracellular transport and retinal degeneration
Authors: Sivagurunathan Suganya , Srikakulam Nagesh , Arunachalam Jayamuruga Pandian , Pandi Gopal , Chidambaram Subbulakshmi
Published: April 2018

Long considered to be active only in germline, PIWI/piRNA pathway is now known to play significant role in somatic cells, especially neurons. Nonetheless, so far there is no evidence for the presence of piRNAs in the neurosensory retina. In this study, we have uncovered 102 piRNAs in human retina and retinal pigment epithelium (RPE) by analysing RNA-seq data. The identified piRNAs were enriched with three motifs predicted to be involved in rRNA processing and sensory perception. Further, expression of piRNAs in donor eyes were assessed by qRT-PCR. Loss of piRNAs in HIWI2 knockdown ARPE19 cells downregulated targets implicated in intracellular transport (SNAREs andRabs), circadian clock (TIMELESS) and retinal degeneration (LRPAP1andRPGRIP1). Moreover, piRNAs were dysregulated under oxidative stress indicating their potential role in retinal pathology. Intriguingly, computational analysis revealed complete and partial seed sequence similarity between piR-62011 and sensory organ specific miR-183/96/182 cluster. Furthermore, the expression of retina enriched piR-62011 positively correlated with miR-182 in HIWI2 silenced Y79 cells. Thus, our data provides an evidence for the expression of piRNAs in human retina and RPE. Collectively, our work demonstrates that piRNAs dynamically regulate distinct molecular events in the maintenance of retinal homeostasis.
Single-Dose Monocrotaline Pyrrole Injection as a Model of Pulmonary Endothelial Injury In Mice
Authors: Raoul William , Hulin Anne , Saber Guitanouch , Boisnier Catherine , Eddahibi Saadia , Adnot Serge , Maitre Bernard
Published: April 2018

Monocrotaline (MCT) is a plant substance that induces severe pulmonary hypertension in several animals except for mice. The aim of our study was to state whether monocrotaline pyrrole (MCTp), the main monocrotaline metabolite, could induce significant injury in mouse lung when given intravenously. MCTp caused moderate pulmonary inflammation, remodelling of small distal vessels (percentage of muscularized arteries: 33,5 vs 20,6%, p≤0,0006) and a right ventricular dysfunction (RVSP 27,8mmHg vs 16,4mmHg, p≤0,0001; Fulton index 0,35 vs 0,26, p≤0,0007). These vascular effects were associated with a decrease in eNOS protein expression in lung tissues and resolved after 45 days. In conclusion, we developed a model of endothelial dysfunction and transient pulmonary hypertension in mice.
USP7 couples DNA replication termination to mitotic entry
Authors: Galarreta Antonio , Lecona Emilio , Valledor Pablo , Ubieto Patricia , Lafarga Vanesa , Specks Julia , Fernandez-Capetillo Oscar
Published: April 2018

To ensure a faithful segregation of chromosomes, DNA must be fully replicated before mitotic entry. However, how cells sense the completion of DNA replication and to what extent this is linked to the activation of the mitotic machinery remains poorly understood. We previously showed that USP7 is a replisome-associated deubiquitinase with an essential role in DNA replication. Here, we reveal that USP7 inhibition leads to the ubiquitination of MCM7, a hallmark of DNA replication termination. In addition, USP7 inhibition leads to the ubiquitination of additional replisome components such as POLD1, which are displaced from replisomes. Surprisingly, this premature termination of DNA replication occurs concomitant to a generalized activation of CDK1 throughout the entire cell cycle, which impairs chromosome segregation and is toxic for mammalian cells. Accordingly, the toxicity of USP7 inhibitors is alleviated by CDK1 inhibition. Our work sheds light into the mechanism of action of USP7 inhibitors and provides evidence to the concept that DNA replication termination is coupled to the activation of the mitotic program.
Simulating multi-level dynamics of antimicrobial resistance in a membrane computing model
Authors: Campos Marcelino , Capilla Rafael , Naya Fernando , Futami Ricardo , Coque Teresa , Moya Andrés , Fernandez-Lanza Val , Cantón Rafael , Sempere José M. , Llorens Carlos , Baquero Fernando
Published: April 2018

Membrane Computing is a bio-inspired computing paradigm, whose devices are the so-called membrane systems or P systems. The P system designed in this work reproduces complex biological landscapes in the computer world. It uses nested “membrane-surrounded entities” able to divide, propagate and die, be transferred into other membranes, exchange informative material according to flexible rules, mutate and being selected by external agents. This allows the exploration of hierarchical interactive dynamics resulting from the probabilistic interaction of genes (phenotypes), clones, species, hosts, environments, and antibiotic challenges. Our model facilitates analysis of several aspects of the rules that govern the multi-level evolutionary biology of antibiotic resistance. We examine a number of selected landscapes where we predict the effects of different rates of patient flow from hospital to the community and viceversa, cross-transmission rates between patients with bacterial propagules of different sizes, the proportion of patients treated with antibiotics, antibiotics and dosing in opening spaces in the microbiota where resistant phenotypes multiply. We can also evaluate the selective strength of some drugs and the influence of the time-0 resistance composition of the species and bacterial clones in the evolution of resistance phenotypes. In summary, we provide case studies analyzing the hierarchical dynamics of antibiotic resistance using a novel computing model with reciprocity within and between levels of biological organization, a type of approach that may be expanded in the multi-level analysis of complex microbial landscapes.