Journal articles on the topic 'Slot adjusting mechanism'

Based on the evanescent wave resonance, a photonic crystal sensing structure with air slot-porous silicon-air slot Fabry–Perot cavity (F–P cavity) is proposed. Taking the F–P cavity as the sensing unit, when the gas to be detected is filled into the sensing unit, the refractive index of the air slot will be changed and the refractive index of the porous silicon layer will also be varied, both of which will shift the resonant peak and greatly increase the sensitivity of the sensor. By adjusting the structural parameters, the quality factor (Q value) can be optimized. A model for the relationship between the resonant wavelength and the refractive index of the detected organic gas was established, and the refractive index sensing performance was analyzed. The results show that the Q value of the structure can attain to 12312.2 and the sensitivity is about 8661.708 nm/RIU, which can provide effective theoretical reference and technical guidance for organic gas detection with low concentration.

A bandwidth allocation algorithm for wireless multimedia sensor networks is proposed in this paper. On the premise ofInitialallocation algorithm based on distortion and congestion model to provide an efficient system performance, the allocation algorithm based on pricing mechanism we proposed balances the real-time requirement of different users by adjusting the bandwidth price in each network and each slot. Simulation results show that the proposed algorithm balances the bandwidth ratio of different users according to the video complexity, and it can provide a good system performance guaranteeing the fairness among the users.

High-order dispersions of the silicon-on-insulator (SOI) waveguides with different shapes (including slab, ridge and slot) have been obtained and compared using the finite element method (FEM). Through adjusting the geometrical parameters of the waveguides, single or dual zero-dispersion wavelengths (ZDWs) can be tuned in the broadband wavelength range. Differences of dispersion curves among these waveguides are analyzed from the viewpoint of structure and mechanism in detail. It is remarkably shown the number of ZDWs can be varied from 0 to 2 and the position of the ZDWs can be tuned from 1400 nm to 1900 nm flexibly. Moreover, the differences of dispersion features in short and long wavelength regions are also discussed deeply. Due to the dispersion of SOI waveguides playing a dominated role in many nonlinear optical effects, this research can make some contribution for dispersion tailoring and nonlinear optics.

In the present study, a set of novel clamping apparatus that could deliver biaxial stretching motions with the use of a uniaxial tensile testing machine was designed and manufactured. The conversion of uniaxial motion into biaxial stretching motions is achieved by a sliding mechanism that consists of two blocks sliding in two mutually perpendicular grooves, respectively. During the biaxial tension test, a cross-shaped specimen sitting in the grooves are stretched by the two blocks driven by a pulling rod. The different stress ratios could be obtained by adjusting the groove surface shape and the lengths of specimen wings. In the clamping apparatus design stage, the finite element simulations were performed to examine the validity of the sliding mechanism and the frictional force generated between the sliding blocks and the grooves. The coefficient of friction was determined afterwards from the comparison of the pulling forces obtained in the experiments with those calculated by the finite element simulations. In addition, the optimum geometry and dimension of the cross-shaped specimen used in the biaxial tension tests were investigated by the finite element analysis as well. The slotted specimen proposed by Kuwabara et al. was taken as the basic design. A sufficiently large area in the central region of specimen where the principal stress directions aligned with the groove direction was obtained for gluing the strain gauges to the specimen for the biaxial stretching tests. The number of slots and associated slot widths were also examined to optimize the shape of the specimens. The proposed clamping apparatus was manufactured and the biaxial tension tests were conducted with cross-shaped specimens made of advanced high strength steel sheets. The validity of the designed clamping apparatus used for biaxial tension tests was confirmed and the congruence of various yield criteria applied to the advanced high strength steel sheets subjected to biaxial stress states was discussed.

In this paper, electromagnetically-induced transparency (EIT) phenomena have been investigated numerically in the plasmonic waveguides composed of unsymmetrical slot shaped metal–insulator–metal (MIM) structures. By the transmission line theory and Fabry–Perot model, the formation and evolution mechanisms of plasmon-induced transparency were exactly analyzed. The analysis showed that the peak of EIT-like transmission could be changed easily according to certain rules by adjusting the geometrical parameters of the slot structures, including the coupling distances and slot depths. We can find a new method to design nanoscale optical switch, devices in optical storage and optical computing.

Wireless network-on-chip (WiNoC) uses a wireless backbone on top of the traditional wired-based NoC which demonstrated high scalability. WiNoC introduces long-range single-hop link connecting distanced core and high bandwidth radio frequency interconnects that reduces multi-hop communication in conventional wired-based NoC. However, to ensure full benefits of WiNoC technology, there is a need for fair and efficient Medium Access Control (MAC) mechanism to enhance communication in the wireless Network-on-Chip. To adapt to the varying traffic demands from the applications running on a multicore environment, MAC mechanisms should dynamically adjust the transmission slots of the wireless interfaces (WIs), to ensure efficient utilization of the wireless medium in a WiNoC. This work presents a prediction model that improves MAC mechanism to predict the traffic demand of the WIs and respond accordingly by adjusting transmission slots of the WIs. This research aims to reduce token waiting time and inefficient decision making for radio hub-to-hub communication and congestion-aware routing in WiNoC to enhance end to end latency. Through system level simulation, we will show that the dynamic MAC using an History-based prediction mechanism can significantly improve the performance of a WiNoC in terms of latency and network throughput compared to the state-of-the-art dynamic MAC mechanisms.

To obtain the flow mechanism of the transient characteristics of a Kaplan turbine, a three-dimensional (3-D) unsteady, incompressible flow simulation during load rejection was conducted using a computational fluid dynamics (CFD) method in this paper. The dynamic mesh and re-meshing methods were performed to simulate the closing process of the guide vanes and runner blades. The evolution of inner flow patterns and varying regularities of some parameters, such as the runner rotation speed, unit flow rate, unit torque, axial force, and static pressure of the monitored points were revealed, and the results were consistent with the experimental data. During the load rejection process, the guide vane closing behavior played a decisive role in changing the external characteristics and inner flow configurations. In this paper, the runner blades underwent a linear needle closure law and guide vanes operated according to a stage-closing law of “first fast, then slow,” where the inflection point was t = 2.3 s. At the segment point of the guide vane closing curve, a water hammer occurs between guide vanes and a large quantity of vortices emerged in the runner and the draft tube. The pressure at the measurement points changes dramatically and the axial thrust rises sharply, marking a unique time in the transient process. Thus, the quality of a transient process could be effectively improved by properly setting the location of segmented point. This study conducted a dynamic simulation of co-adjustment of the guide vanes and the blades, and the results could be used in fault diagnosis of transient operations at hydropower plants.

We tested the hypothesis that vasoregulatory mechanisms exist in humans that can rapidly adjust muscle blood flow to repeated increases and decreases in exercise intensity. Six men and seven women (age, 24.4 ± 1.3 yr) performed continuous dynamic forearm handgrip contractions (1- to 2-s contraction-to-relaxation duty cycle) during repeated step increases and decreases in contraction intensity. Three step change oscillation protocols were examined: Slow (7 contractions per contraction intensity × 10 steps); Fast (2 contractions per contraction intensity × 15 steps); and Very Fast (1 contraction per contraction intensity × 15 steps). Forearm blood flow (FBF; Doppler and echo ultrasonography), heart rate (ECG), and mean arterial pressure (arterial tonometry) were examined for the equivalent of a cardiac cycle during each relaxation phase (FBFrelax). Mean arterial pressure and heart rate did not change during repeated step changes ( P = 0.352 and P = 0.190). For both Slow and Fast conditions, relaxation phase FBFrelax adjusted immediately and repeatedly to both increases and decreases in contraction intensity, and the magnitude and time course of FBFrelax changes were virtually identical. For the Very Fast condition, FBFrelax increased with the first contraction and thereafter slowly increased over the course of repeated contraction intensity oscillations. We conclude that vasoregulatory mechanisms exist in human skeletal muscle that are capable of rapidly and repeatedly adjusting muscle blood flow with ongoing step changes in contraction intensity. Importantly, they demonstrate symmetry in response magnitude and time course with increasing versus decreasing contraction intensity but cannot adjust to very fast exercise intensity oscillations.

This review examines the evidence that skeletal muscles can sense the status of the peripheral vascular network through group III and IV muscle afferent fibers. The anatomic and neurophysiological basis for such a mechanism is the following: 1) a significant portion of group III and IV afferent fibers have been found in the vicinity and the adventitia of the arterioles and the venules; 2) both of these groups of afferent fibers can respond to mechanical stimuli; 3) a population of group III and IV fibers stimulated during muscle contraction has been found to be inhibited to various degrees by arterial occlusion; and 4) more recently, direct evidence has been obtained showing that a part of the group IV muscle afferent fibers is stimulated by venous occlusion and by injection of vasodilatory agents. The physiological relevance of sensing local distension of the vascular network at venular level in the muscles is clearly different from that of the large veins, since the former can directly monitor the degree of tissue perfusion. The possible involvement of this sensing mechanism in respiratory control is discussed mainly in the light of the ventilatory effects of peripheral vascular occlusions during and after muscular exercise. It is proposed that this regulatory system anticipates the chemical changes that would occur in the arterial blood during increased metabolic load and attempts to minimize them by adjusting the level of ventilation to the level of muscle perfusion, thus matching the magnitudes of the peripheral and pulmonary gas exchange.

Every node has the states of its neighbors such as Selfish, Unselfish and No Information state. The selfish node free path is constructed by avoiding selfish node in the route discovery process. Watch Dog mechanism helps to avoid such issues. Price and Reputation system (P&RS) helps to diminish the selfish nodes in a successful manner. Trustable node with low portability will go about as a Notoriety Manager and it keeps every one of the records of every node in a record system. The overload of RA leads to various problem and makes the communication very slow. In this paper we discuss about the RA affiliation and request in various possible ways. RA sends the affiliation to the nearest relay node to act as a RA for few nodes. Moreover we discuss the RA communication with Internet through Gateways and the load balancing algorithm – Energy Share Load Balancing Algorithm (ESLBA). The heap adjusting algorithm shares the heap between the nodes and channelizes the ideal course smarterly.

1. The gastric mill central pattern generator (CPG) controls the chewing movements of teeth in the gastric mill of the lobster. This CPG has been extensively studied, but the precise mechanism underlying pattern generation is not well understood. The goal of this research was to develop a simplified model that captures the principle, biologically significant features of this CPG. We introduce a simplified neuron model that embodies approximations of well-known membrane currents, and is able to reproduce several global characteristics of gastric mill neurons. A network built with these neurons, using graded synaptic transmission and having the synaptic connections of the biological circuit, is sufficient to explain much of the network's behavior. 2. The cell model is a generalization and extension of the Van der Pol relaxation oscillator equations. It is described by two differential equations, one for current conservation and one for slow current activation. The model has a fast current that may, by adjusting one parameter, have a region of negative resistance in its current-voltage (I-V) curve. It also has a slow current with a single gain parameter that can be regarded as the combination of slow inward and outward currents. 3. For suitable values of the fast current parameter and the slow current parameter, the isolated model neuron exhibits several different behaviors: plateau potentials, postinhibitory rebound, postburst hyperpolarization, and endogenous oscillations. When the slow current is separated into inward and outward fractions with separately adjustable gain parameters, the model neuron can fire tonically, be quiescent, or generate spontaneous voltage oscillations with varying amounts of depolarization or hyperpolarization. 4. The most common form of synaptic interaction in the gastric CPG is reciprocal inhibition. A pair of identical model cells, connected with reciprocal inhibition, oscillates in antiphase if either the isolated cells are endogenous oscillators, or they are quiescent without plateau potentials, or they have plateau potentials but the synaptic strengths are below a critical level. If the isolated cells have widely differing frequencies (or would have if the cells were made to oscillate by adjusting the fast currents), reciprocal inhibition entrains the cells to oscillate with the same frequency but with phases that are advanced or retarded relative to the phases seen when the cells have the same frequency. The frequency of the entrained pair of cells lies between the frequencies of the original cells. The relative phases can also be modified by using very unequal synaptic strengths.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract White matter lesions (WML) are highly prevalent in older adults and thought to represent cerebral microvascular disease, contributing to slow gait and dementia. Hypertension is associated with WML. However, the underlying mechanism of this association is unclear. The complex beat-to-beat BP fluctuations represent the influence of BP regulatory mechanisms over multiple time scales. The association between WML and abnormalities in BP regulation may be manifest as a loss of complexity in BP dynamics. The aim of this study is thus to explore the relationships between hypertension, BP complexity, and WML in older adults. Twenty-two older adults with hypertension (SBP>140 mmHg) and 19 age-matched older adults without hypertension (i.e., control) completed this study. Their whole-brain WML were assessed by two neurologists using the Fazekas Scale. Greater score reflects higher WML grade. Each participant completed a 10-minute BP assessment when sitting quietly following the MRI. The continuous SBP and DBP series were recorded, and the complexity of them was quantified using multiscale entropy (MSE). Lower MSE reflects lower complexity. Compared to the controls, hypertensives had significantly greater Fazekas scores (i.e., higher WML grade) (F=4.8, p=0.02) and lower complexity of SBP and DBP (F>3.7, p<0.01), after adjusting for age. Across two cohorts, those with lower SBP and DBP complexity had higher Fazekas score (r<-0.51, p<0.01), and this association was independent of age and group. These results suggest that WML are associated with a loss of complexity in BP dynamics. Future longitudinal studies are needed to examine the causal relationship between WML and BP.

A novel refractive index nanosensor with compound structures is proposed in this paper. It consists of three different kinds of resonators and two stubs which are side-coupled to a metal–dielectric–metal (MDM) waveguide. By utilizing numerical investigation with the finite element method (FEM), the simulation results show that the transmission spectrum of the nanosensor has as many as five sharp Fano resonance peaks. Due to their different resonance mechanisms, each resonance peak can be independently tuned by adjusting the corresponding parameters of the structure. In addition, the sensitivity of the nanosensor is found to be up to 1900 nm/RIU. For practical application, a legitimate combination of various different components, such as T-shaped, ring, and split-ring cavities, has been proposed which dramatically reduces the nanosensor dimensions without sacrificing performance. These design concepts pave the way for the construction of compact on-chip plasmonic structures, which can be widely applied to nanosensors, optical splitters, filters, optical switches, nonlinear photonic and slow-light devices.

ABSTRACTPeople in regions ofSchistosoma mansoniendemicity slowly acquire immunity, but why this takes years to develop is still not clear. It has been associated with increases in parasite-specific IgE, induced, some investigators propose, to antigens exposed during the death of adult worms. These antigens include members of the tegumental-allergen-like protein family (TAL1 to TAL13). Previously, in a group ofS. mansoni-infected Ugandan males, we showed that IgE responses to three TALs expressed in worms (TAL1, -3, and -5) became more prevalent with age. Now, in a subcohort we examined associations of these responses with resistance to reinfection and use the data to propose a mechanism for the slow development of immunity. IgE was measured 9 weeks posttreatment and at reinfection at 2 years (n= 144). An anti-TAL5 IgE (herein referred to as TAL5 IgE) response was associated with reduced reinfection even after adjusting for age using regression analysis (geometric mean odds ratio, 0.24;P= 0.016). TAL5 IgE responders were a subset of TAL3 IgE responders, themselves a subset of TAL1 responders. TAL3 IgE and TAL5 IgE were highly cross-reactive, with TAL3 the immunizing antigen and TAL5 the cross-reactive antigen. Transcriptional and translational studies show that TAL3 is most abundant in adult worms and that TAL5 is most abundant in infectious larvae. We propose that in chronic schistosomiasis, older individuals have repeatedly experienced IgE antigens exposed when adult worms die (e.g., TAL3) and that this leads to increasing cross-reactivity with antigens of invading larvae (e.g., TAL5). Progressive accumulation of worm/larvae cross-reactivity could explain the age-dependent immunity observed in areas of endemicity.

Type 2 diabetes mellitus accelerates loss of muscle mass and strength. Patients with Alzheimer’s disease (AD) also show these conditions, even in the early stages of AD. The mechanism linking glucose management with these muscle changes has not been elucidated but has implications for clarifying these associations and developing preventive strategies to maintain functional capacity. This study included 69 type 2 diabetes patients with a diagnosis of cognitive impairment (n = 32) and patients with normal cognition (n = 37). We investigated the prevalence of sarcopenia in diabetes patients with and without cognitive impairment and examined the association of glucose alterations with sarcopenia. Daily glucose levels were evaluated using self-monitoring of blood glucose, and we focused on the effects of glucose fluctuations, postprandial hyperglycemia, and the frequency of hypoglycemia on sarcopenia. Diabetes patients with cognitive impairment displayed a high prevalence of sarcopenia, and glucose fluctuations were independently associated with sarcopenia, even after adjusting for glycated hemoglobin A1c (HbA1c) levels and associated factors. In particular, glucose fluctuations were significantly associated with a low muscle mass, low grip strength, and slow walking speed. Our observation suggests the importance of glucose management by considering glucose fluctuations to prevent the development of disability.

Closing the carbon cycle by the electrochemical reduction of CO2 to formic acid and other high-value chemicals is a promising strategy to mitigate rapid climate change. The main barriers to commercializing a CO2 reduction reaction (CO2RR) system for formate production are the chemical inertness, low aqueous solubility, and slow mass transport characteristics of CO2, along with the low selectivity and high overpotential observed in formate production via CO2 reduction. To address those problems, we first explain the possible reaction mechanisms of CO2RRs to formate, and then we present and discuss several strategies to overcome the barriers to commercialization. The electronic structure of the catalyst can be tuned to favor a specific intermediate by adjusting the catalyst composition and tailoring the facets, edges, and corners of the catalyst to better expose the active sites, which has primarily led to increased catalytic activity and selectivity. Controlling the local pH, employing a high-pressure reactor, and using systems with three-phase boundaries can tune the mass transport properties of reactants at the catalyst surface. The reported electrocatalytic performances are summarized afterward to provide insight into which strategies have critical effects on the production of formate.

AbstractPlants and bacteria respond to hyperosmotic stress by an increase in intracellular osmolality, adjusting their cell turgor to altered growth conditions. This can be achieved either by increased uptake orde novosynthesis of a variety of organic osmolytes (so-called ‘compatible solutes’), or by controlling fluxes of ions across cellular membranes. The relative contributions of each of these mechanisms have been debated in literature for many years and remain unresolved. This paper summarises all the arguments and reopens a discussion on the efficiency and strategies of osmotic adjustment in plants and bacteria. We show that the bulk of osmotic adjustment in both plants and bacteria is achieved by increased accumulation of inorganic osmolytes such as K+, Na+and Cl-. This is applicable to both halophyte and glycophyte species. At the same time,de novosynthesis of compatible solutes is an energetically expensive and slow option and can be used only for the fine adjustment of the cell osmotic potential. The most likely role the organic osmolytes play in osmotic adjustment is in osmoprotection of key membrane transport proteins and reactive oxygen species (ROS) scavenging. The specific mechanisms by which compatible solutes regulate activity of ion transporters remain elusive and require more thorough investigation. It is concluded that creating transgenic species with increased levels of organic osmolytes by itself is counterproductive due to high yield penalties; all these attempts should be complemented by a concurrent increase in the accumulation of inorganic ions directly used for osmotic adjustment.

Overcoming the slow-leaching kinetics of refractory primary copper sulfides is crucial to secure future copper sources. Here, the effect of carbon was investigated as a catalyst for a bioleaching reaction. First, the mechanism of carbon-assisted bioleaching was elucidated using the model chalcopyrite mineral, under specified low-redox potentials, by considering the concept of Enormal. The carbon catalyst effectively controlled the Eh level in bioleaching liquors, which would otherwise exceed its optimal range (0 ≤ Enormal ≤ 1) due to active regeneration of Fe3+ by microbes. Additionally, Enormal of ~0.3 was shown to maximize the carbon-assisted bioleaching of the model chalcopyrite mineral. Secondly, carbon-assisted bioleaching was tested for three types of chalcopyrite/enargite-bearing complex concentrates. A trend was found that the optimal Eh level for a maximum Cu solubilization increases in response to the decreasing chalcopyrite/enargite ratio in the concentrate: When chalcopyrite dominates over enargite, the optimal Eh was found to satisfy 0 ≤ Enormal ≤ 1. As enargite becomes more abundant than chalcopyrite, the optimal Eh for the greatest Cu dissolution was shifted to higher values. Overall, modifying the Eh level by adjusting AC doses to maximize Cu solubilization from the concentrate of complex mineralogy was shown to be useful.

Based on the urgent needs for high transmission speed and high reliability of wireless MWD, the OQPSK modulation of the drilling fluid continuous wave signal is proposed in this article. The Principle of delay orthogonal modulation and coherent demodulation of OQPSK are studied, and the changes in the phase vector of the inputted bit sequence are analyzed; according to the principle of continuous wave generation, the phase adjustment mechanism of rotary value are analyzed and the relationship between the signal waveform, as well as the rotational speed when adjusting the phase, is studied; the information transmission rate, band efficiency and bit error rate of the OQPSK and QDPSK continuous wave communication systems are comparatively analyzed and simulated. The results show that OQPSK eliminates the phase transition of π, which belongs to constant envelope modulation, is suitable for the transmission under low SNR drilling fluid channel, meanwhile simplifies the phase adjustment and reduces generator design. QDPSK can simplify the computational complexity of phase adjustment, and reduces the design difficulty of the continuous-wave generator’s control circuit. The rotary valve forms of "slow down - speed up" and " speed up - slow down " are suitable for π / 2 and 3π / 2 phase jump respectively; the motor control modes which combine closed loop position and closed loop velocity can achieve phase stable signal and reduce the dynamic torque of the motor; in the same carrier frequency and SNR, the information rate and bandwidth efficiency of both OQPSK’s and QDPSK’s are twice as those of the two-phase shift keying system’s, and they can improve the wireless transmission performance of MWD system.

AbstractIncreasing the surface hydrophilicity of polyetherimide (PEI) through partial hydrolysis of the imide groups while maintaining the length of the main-chain was explored for adjusting its function in biomedical and membrane applications. The outcome of the polymer analogous reaction, i.e., the degree of ring opening and chain cleavage, is difficult to address in bulk and microstructured systems, as these changes only occur at the interface. Here, the reaction was studied at the air–water interface using the Langmuir technique, assisted by atomic force microscopy and vibrational spectroscopy. Slow PEI hydrolysis sets in at pH > 12. At pH = 14, the ring opening is nearly instantaneous. Reduction of the layer viscosity with time at pH = 14 suggested moderate chain cleavage. No hydrolysis was observed at pH = 1. Hydrolyzed PEI films had a much more cohesive structure, suggesting that the nanoporous morphology of PEI can be tuned via hydrolysis. Graphic abstract

Neural network models have recently made significant achievements in solving vehicle scheduling problems. Adaptive ant colony algorithm provides a new idea for neural networks to solve complex system problems of multiconstrained network intensive vehicle routing models. The pheromone in the path is changed by adjusting the volatile factors in the operation process adaptively. It effectively overcomes the tendency of the traditional ant colony algorithm to fall easily into the local optimal solution and slow convergence speed to search for the global optimal solution. The multiconstrained network intensive vehicle routing algorithm based on adaptive ant colony algorithm in this paper refers to the interaction between groups. Adaptive transfer and pheromone update strategies are introduced based on the traditional ant colony algorithm to optimize the selection, update, and coordination mechanisms of the algorithm further. Thus, the search task of the objective function for a feasible solution is completed by the search ants. Through the division and collaboration of different kinds of ants, pheromone adaptive strategy is combined with polymorphic ant colony algorithm. It can effectively overcome some disadvantages, such as premature stagnation, and has a theoretical significance to the study of large-scale multiconstrained vehicle routing problems in complex traffic network systems.

Digestive and metabolic processes are entrained by restricted feeding (RFS) schedules and are thought to be potential elements of a food-entrained oscillator (FEO). Due to the close relationship of leptin with metabolic regulation and because leptin is a relevant communication signal of the individual's peripheral metabolic condition with the central nervous system, we explored whether leptin is an endogenous entraining signal from the periphery to a central element of an FEO. First we characterized in the rat the diurnal rhythm of serum leptin (in rats fed ad libitum (AL)), its adjustment to an RFS and the influence of fasting after RFS, or RFS followed by AL feeding and then total food deprivation (RF-AF) in the persistence of this fluctuating pattern. We also explored the response of free fatty acids and stomach weight under the same entraining conditions. We compared the metabolic response with the behavioral expression of drinking anticipatory activity (AA) under the same conditions. Finally, we tested the effect of daily i.c.v administration of leptin as a putative entraining signal for the generation of AA.Metabolic parameters responded to food entrainment by adjusting their phase to mealtime. However, leptin and free fatty acid rhythms persisted only for a few cycles in fasting conditions and readjusted to the light-darkness cycle after an RF-AF protocol. In contrast, behavioral food-entrained rhythms persisted after both fasting manipulations. Daily leptin i.c.v. administration did not produce AA, nor produce changes in the behavioral free-running rhythm. Stomach weight indicated an adaptive process allowing an extreme stomach distension followed by a slow emptying process, which suggests that the stomach may be playing a relevant role as a storage organ. In conclusion, metabolic signals here studied respond to feeding schedules by adjusting their phase to mealtime, but do only persist for a few cycles in fasting. Leptin does not produce AA and thus is not an entraining signal for FEO. The response of metabolic signals to feeding schedules depends on different mechanisms than the expression of AA.

We study theoretically the Fano resonances (FRs) produced by the near-field coupling between the lowest-order (dipolar) sphere plasmon resonance and the dipolar cavity plasmon mode supported by an Ag nanoshell or the hybrid mode in a simple three-layered Ag nanomatryushka constructed by incorporating a solid Ag nanosphere into the center of Ag nanoshell. We find that the linewidth of dipolar cavity plasmon resonance or hybrid mode induced FR is as narrow as 6.8 nm (corresponding to a high Q-factor of ~160 and a long dephasing time of ~200 fs) due to the highly localized feature of the electric-fields. In addition, we attribute the formation mechanisms of typical asymmetrical Fano line profiles in the extinction spectra to the constructive (Fano peak) and the destructive interferences (Fano dip) arising from the symmetric and asymmetric charge distributions between the dipolar sphere and cavity plasmon or hybrid modes. Interestingly, by simply adjusting the structural parameters, the dielectric refractive index required for the strongest FR in the Ag nanomatryushka can be reduced to be as small as 1.4, which largely reduces the restriction on materials, and the positions of FR can also be easily tuned across a broad spectral range. The ultranarrow linewidth, highly tunability together with the huge enhancement of electric fields at the FR may find important applications in sensing, slow light, and plasmon rulers.

Oscillatory neural activity is dynamically controlled to coordinate perceptual, attentional and cognitive processes. On the macroscopic scale, this control is reflected in the U-shaped deviations of EEG spectral-power dynamics from stochastic dynamics, characterized by disproportionately elevated occurrences of the lowest and highest ranges of power. To understand the mechanisms that generate these low- and high-power states, we fit a simple mathematical model of synchronization of oscillatory activity to human EEG data. The results consistently indicated that the majority (~95%) of synchronization dynamics is controlled by slowly adjusting the probability of synchronization while maintaining maximum entropy within the timescale of a few seconds. This strategy appears to be universal as the results generalized across oscillation frequencies, EEG current sources, and participants (N = 52) whether they rested with their eyes closed, rested with their eyes open in a darkened room, or viewed a silent nature video. Given that precisely coordinated behavior requires tightly controlled oscillatory dynamics, the current results suggest that the large-scale spatial synchronization of oscillatory activity is controlled by the relatively slow, entropy-maximizing adjustments of synchronization probability (demonstrated here) in combination with temporally precise phase adjustments (e.g., phase resetting generated by sensorimotor interactions). Interestingly, we observed a modest but consistent spatial pattern of deviations from the maximum-entropy rule, potentially suggesting that the mid-central-posterior region serves as an “entropy dump” to facilitate the temporally precise control of spectral-power dynamics in the surrounding regions.

In the production process at PT X, such as casting process, required raw material in the form of casting sand. The sand transport process is done by a machine called a Bucket Elevator. The current condition of Bucket Elevator at Plant 2 PT X had some problems on its design due to the initial modification process to the machine that were deliberately done in order to ease the process of troubleshooting and repair on the machine to adjust the height of the drum shaft supported by the bearing, however, the modification causes a sand leak that impacted the lifetime of the bearing. The damage that occurs to the bearing of the Bucket Elevator can slow the production process at PT X down, which lasts between 120 hours to 134 hours per week. Therefore, it is necessary to modify the design of the Bucket Elevator machine in order to stop the sand leakage and be able to work optimally. The design modifications made, are changes to the shaft height adjusting mechanism of the Bucket Elevator 536 drum machine by providing a lock to minimize the leakage of sand that occurs and replace the bearing type to the type that is equipped with a seal to prevent the entry of sand into the bearings. The result of this modification can extend the lifetime bearing, thereby reducing production costs due to bearing replacement, and easing the troubleshooting and repairing process of the engine to adjust the height of the drum shaft supported by the bearings.

9065 Background: Ipilimumab was the first agent approved for the treatment of unresectable or metastatic melanoma that showed an overall survival benefit in randomised phase III trials. Early clinical studies explored the potential relationship between immune-related adverse events (irAEs) associated with ipilimumab and antitumor activity but no definitive conclusion has been reached. Here, we evaluated the possible correlation between efficacy of ipilimumab treatment and irAEs in patients (pts) enrolled in the EAP in Italy. Methods: Ipilimumab was available upon physician request for pts aged ≥16 years with unresectable stage III/stage IV melanoma who had either failed systemic therapy or were intolerant to ≥1 systemic treatment and for whom no other therapeutic option was available. Ipilimumab 3 mg/kg was administered intravenously every 3 weeks for 4 doses. Tumour assessments were conducted at baseline and after completion of induction therapy using immune-related response criteria. Pts were monitored for adverse events (AEs), including immune-related AEs (irAEs), using Common Terminology Criteria for Adverse Events v.3.0. Results: In total, 855 Italian pts participated in the EAP from June 2010 to April 2012 across 55 centres. Among 833 evaluable pts, 278 pts (33.4%) reported an irAE and 555 (66.6%) did not. As of December 2012, the disease control rates among pts with or without irAEs were 35.3% and 33.9% respectively. We noted that there was a difference in the distribution of pts with or without irAEs among pts who experienced a fast progression, thus not being able to receive at least 3 cycles, and pts with slow progression. In fact, due to the mechanism of action of the drug and consequent delayed onset of irAEs, pts with irAEs among fast and slow progressors were 22% and 37% respectively. Therefore, median overall survival was evaluated by adjusting the 2 groups for this factor and results showed a comparable survival between pts who reported an irAE and pts who did not (10.0 vs 9.7 months respectively). Conclusions: This exploratory analysis of EAP data suggest that activity and efficacy of ipilimumab is not related with the occurrence of irAEs.

Saccades are the rapid eye movements used to change visual fixation. Normal saccades end abruptly with very little postsaccadic ocular drift, but acute ocular motor deficits can cause the eyes to drift appreciably after a saccade. Previous studies in both patients and monkeys with peripheral ocular motor deficits have demonstrated that the brain can suppress such postsaccadic drifts. Ocular drift might be suppressed in response to visual and/or proprioceptive feedback of position and/or velocity errors. This study attempts to characterize the adaptive mechanism for suppression of postsaccadic drift. The responses of seven rhesus monkeys were studied to postsaccadic retinal slip induced by horizontal exponential movements of a full-field stimulus. After several hours of saccade-related retinal image slip, the eye movements of the monkeys developed a zero-latency, compensatory postsaccadic ocular drift. This ocular drift was still evident in the dark, although smaller (typically 15% of the amplitude of the antecedent saccade, up to a maximum drift of 8 degrees). Retinal slip alone, without a net displacement of the image, was sufficient to elicit these adaptive changes, and compensation for leftward and rightward saccades was independent. It took several days to complete adaptation, but recovery (in the light) was much quicker. The decay of this adaptation in darkness was very slow; after 3 days the ocular drift was reduced by less than 50%. The time constants of single exponential curve fits to adaptation time courses of data from five animals were 35 h for acquisition, 4 h for recovery, and at least 40 h for decay in darkness. Descriptions of the central innervation for a saccade are usually simplified to only two components: a pulse and a step. It has been hypothesized that suppression of pathological postsaccadic drift is achieved by adjusting the ratio of the pulse to the step of innervation (19, 26). However, we show that the time constant of the ocular drift is influenced by the time constant of the adapting stimulus, which cannot be explained by the simple pulse-step model of saccadic innervation. A more realistic representation of the saccadic innervation has three components: a pulse, an exponential slide, and a step. Normal saccades were accurately simulated by a fourth-order, linear model of the ocular motor plant driven by such a pulse-slide-step combination. Saccades made after prolonged exposure to optically induced retinal image slip could also be simulated by properly adjusting the slide and step components.(ABSTRACT TRUNCATED AT 400 WORDS)

Misslisch, H., D. Tweed, and T. Vilis. Neural constraints on eye motion in human eye-head saccades. J. Neurophysiol. 79: 859–869, 1998. We examined two ways in which the neural control system for eye-head saccades constrains the motion of the eye in the head. The first constraint involves Listing's law, which holds ocular torsion at zero during head-fixed saccades. During eye-head saccades, does this law govern the eye's motion in space or in the head? Our subjects, instructed to saccade between space-fixed targets with the head held still in different positions, systematically violated Listing's law of the eye in space in a way that approximately, but not perfectly, preserved Listing's law of the eye in head. This finding implies that the brain does not compute desired eye position based on the desired gaze direction alone but also considers head position. The second constraint we studied was saturation, the process where desired-eye–position commands in the brain are “clipped” to keep them within an effective oculomotor range (EOMR), which is smaller than the mechanical range of eye motion. We studied the adaptability of the EOMR by asking subjects to make head-only saccades. As predicted by current eye-head models, subjects failed to hold their eyes still in their orbits. Unexpectedly, though, the range of eye-in-head motion in the horizontal-vertical plane was on average 31% smaller in area than during normal eye-head saccades, suggesting that the EOMR had been reduced by effort of will. Larger reductions were possible with altered visual input: when subjects donned pinhole glasses, the EOMR immediately shrank by 80%. But even with its reduced EOMR, the eye still moved into the “blind” region beyond the pinhole aperture during eye-head saccades. Then, as the head movement brought the saccade target toward the pinhole, the eyes reversed their motion, anticipating or roughly matching the target's motion even though it was still outside the pinhole and therefore invisible. This finding shows that the backward rotation of the eye is timed by internal computations, not by vision. When subjects wore slit glasses, their EOMRs shrank mostly in the direction perpendicular to the slit, showing that altered vision can change the shape as well as the size of the EOMR. A recent, three-dimensional model of eye-head coordination can explain all these findings if we add to it a mechanism for adjusting the EOMR.

Abstract Introduction Risk factors for frailty, including low physical activity and chronic pain, are common among people with osteoarthritis. The aim of this analysis was to determine the association between osteoarthritis and frailty and to determine whether comorbidities interact additively with OA to increase the likelihood of frailty. Methods Men and women aged 40-69 years who contributed to the UK Biobank were analysed. Data about self-reported physician-diagnosed diseases was collected, as well physical measurements, including hand-grip strength. Frailty (robust, pre-frail, frail) was assessed using a modified frailty phenotype, comprising five components: low grip strength, slow walking speed, weight loss, low physical activity, and exhaustion. The association between osteoarthritis and the frailty phenotype was determined using negative binomial regression, adjusting for age, sex, body mass index, smoking status, and Townsend deprivation score. We calculated the attributable proportion of risk of frailty due to additive interaction between osteoarthritis and common co-morbidities (cardiovascular disease, diabetes, COPD, and depression). Results 457,561 people were included, 35,884 (7.8%) had osteoarthritis. The adjusted relative risk ratio (95% CI) for pre-frailty and frailty (versus robust), respectively was higher among people with (versus without) osteoarthritis: 1.58 (1.54, 1.62) and 3.41 (3.26, 3.56). There was significant additive interaction between the presence of osteoarthritis and each of the co-morbidities considered in increasing risk of frailty, particularly diabetes (attributable proportion of risk due to additive interaction with osteoarthritis (95% CI)), 0.49 (0.42, 0.55), coronary heart disease 0.48 (0.41, 0.55), and depression 0.47 (0.41, 0.53). Conclusions Our results suggest that people with OA are at increased risk of pre-frailty and frailty. The mechanisms are not fully understood, though co-morbidity appears to contribute to the risk of frailty beyond the expected additivity of risk due to OA and co-morbidity. Early diagnosis and optimal management of co-morbidities in people with OA may be beneficial.

Summary In this study, single-phase gas-flow simulation that considers slippage effects through a network of slots and microfractures is presented. The statistical parameters for network construction were extracted from petrographic work in tight porous media of the Nikanassin Group in the Western Canada Sedimentary Basin (WCSB). Furthermore, correlations between Klinkenberg slippage effect and absolute permeability have been developed as well as a new unified flow model in which Knudsen number acts implicitly as a flow-regime indicator. A detailed understanding of fluid flow at microscale levels in tight porous media is essential to establish and develop techniques for economic flow rate and recovery. Choosing an appropriate equation for flow through a single element of the network is crucial; this equation must include geometry and other structural features that affect the flow as well as all variation of fluid properties with pressure. Disregarding these details in a single element of porous media can easily lead to flow misinterpretation at the macroscopic scale. Because of the wide flow-path-size distribution in tight porous media, a variety of flow regimes can exist in the equivalent network. Two distinct flow regimes, viscous flow and free molecular flow, are in either side of this flow-regime spectrum. Because the nature of these two types of flow is categorically different, finding/adjusting a unified flow model is problematic. The complication stems from the fact that the viscosity concept misses its meaning as the flow regime changes from viscous to free molecular flow in which a diffusion-like mechanism dominates. For each specified flow regime, the appropriate equations for different geometries are studied. In addition, different unified flow models available in the literature are critically investigated. Simulation of gas flow through the constructed network at different mean flow pressures leads to investigating the functionality of the Klinkenberg factor with permeability of the porous media and pore-level structure.

A physical, model-based approach to body temperatures in dinosaurs allows us to predict what ranges of body temperatures and what thermoregulatory strategies were available to those dinosaurs. We argue that 1.The huge range of body sizes in the dinosaurs likely resulted in very different thermal problems and strategies for animals at either end of this size continuum.2.Body temperatures of the smallest adult dinosaurs and of hatchlings and small juveniles would have been largely insensitive to metabolic rates in the absence of insulation. The smallest animals in which metabolic heating resulted in predicted body temperatures ≥ 2°C above operative temperatures (Te) weigh 10 kg. Body temperature would respond rapidly enough to changes in Te to make behavioral thermoregulation possible.3.Body temperatures of large dinosaurs (>1000 kg) likely were sensitive to both metabolic rate and the delivery of heat to the body surface by blood flow. Our model suggests that they could adjust body temperature by adjusting metabolic rate and blood flow. Behavioral thermoregulation by changing microhabitat selection would likely have been of limited utility because body temperatures would have responded only slowly to changes in Te.4.Endothermic metabolic rates may have put large dinosaurs at risk for overheating unless they had adaptations to shed the heat as necessary. This would have been particularly true for dinosaurs with masses > 10,000 kg, but simulations suggest that for animals as small as 1000 kg in the Tropics and in temperate latitudes during the summer, steady-state body temperatures would have exceeded 40°C. Slow response of body temperatures to changes in Te suggests that use of day-night thermal differences would have buffered dinosaurs from diel warming but would not have lowered body temperatures sufficiently for animals experiencing high mean daily Te.5.Endothermic metabolism and metabolic heating might have been useful for intermediate and large-sized (100–3000 kg) dinosaurs but often in situations that demanded marked seasonal adjustment of metabolic rates and/or precise control of metabolism (and heat-loss mechanisms) as typically seen in endotherms.

1. The visual control of translatory movements in the desert locust Schistocerca gregaria was investigated under open-loop conditions. When locusts were flown tethered in a wind tunnel, wind drift, visually simulated by ground pattern motion either in line with or transverse to their long body axis, induced a modulation of yaw-torque, thrust and lift correlated with the reversal of the direction of motion. 2. Yaw-torque and thrust responses were independent of each other. Spontaneous modulation of amplitude and differences in the time course of these responses indicate that a gain control mechanism is involved in the conversion of the visual stimuli to a behavioural response. 3. Two opposing types of response were observed for each flight parameter and they were found equally often. They were elicited by either transverse or longitudinal pattern motion. The polarity of yaw-torque, thrust or lift responses was thus either positively or negatively correlated with the direction of pattern motion and was preserved throughout an experiment or reversed repeatedly. 4. The yaw responses revealed a tendency for locusts to orient either upwind or downwind under the same stimulus situation. Modulations of thrust and lift confirm that locusts compensate for deviations of the retinal image flow from a preferred value by adjusting both air speed and altitude in free flight. They either speed up or slow down and either increase or decrease flight altitude under the same stimulus situation. 5. The visually induced turning tendency often interacts with a variable internal turning tendency. The internal turning tendency might be responsible for the orientation menotactic to wind seen in the field. 6. The threshold of optomotor responses in the visual control of translation is below 0.15°s−1 for both transverse and longitudinal pattern motion, indicating that wind-related orientation can occur at altitudes of several hundred metres. 7. The orientation behaviour of locusts subjected to visually simulated wind drift depended on the transverse and longitudinal components of pattern motion and on internal factors. The observed variability of response is assumed to result from the locust's ability to modulate independently the gain and sign of the optomotor responses for yaw-torque, thrust and lift.

We have investigated the mechanism of the inhibition of phagosome-lysosome (P-L) fusion in macrophages known to occur after infection by Mycobacterium tuberculosis and by the mouse pathogen Mycobacterium microti. We have used an M. microti infection and have studied, first, the saltatory movements of periphagosomal secondary lysosomes by means of visual phase-contrast microscopy (a similar use of the method having been previously supported by computer analyses). The movements became slow or static after ingestion of live but not of heat-killed M. microti. They were unaffected by a fusiogenic mycobacterium M. lepraemurium. Second, we studied the behavior of a normally fusiogenic unrelated organism, Saccharomyces cerevisiae, after its phagocytosis by cells already containing live M. microti ingested 18 h previously. We observed, using a fluorescent assay of fusion, that many of these yeast phagosomes now also failed to fuse with the lysosomes; in contrast, when the host M. microti had been heat killed the yeast phagosomes fused normally. These observations were extended by ultrastructural quantitative analyses of P-L fusion, which confirmed the nonfusion of phagosomes of live M. microti and, more particularly, the change to nonfusion from the normal fusion behavior of the separate phagosomes of accompanying yeasts. Third, we have assembled evidence against the likelihood that these M. microti-induced phenomena are nonspecific, i.e., secondary to a general depression of activity of heavily infected host cells. The evidence includes the feasibility of adjusting the degree of infection so as to facilitate visual assessment of organelle movements without the presence of detectable damage to the cells studied; the absence of lysosomal stasis after comparable infection with another mycobacterium of comparable virulence (M. lepraemurium); and the reversibility of the stasis. We conclude that inhibition of lysosome saltatory movements (and consequently its secondary effect on the associated yeasts) is a significant, specifically induced phenomenon. From these observations and considerations, therefore, in conjunction with the analogous inhibition of lysosomal movements in normal macrophages by some chemical inhibitors of P-L fusion, and our suggestion that this association is causally related, we now suggest that M. microti-induced focal lysosomal stasis is also the main means by which the inhibition of P-L fusion is brought about by this organism. This concept is strengthened by the observations on S. cerevisiae, which provide strong evidence that stasis can cause suppression of fusion.

ABSTRACT BACKGROUND: Gastroesophageal reflux disease (GERD) is a clinical condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Transient lower esophageal sphincter relaxation is the main pathophysiological mechanism of GERD. Symptoms and complications can be related to the reflux of gastric contents into the esophagus, oral cavity, larynx and/or the lung. Symptoms and other possible manifestations of GERD are heartburn, regurgitation, dysphagia, non-cardiac chest pain, chronic cough, chronic laryngitis, asthma and dental erosions. The proton pump inhibitor (PPI) is the first-choice drug and the most commonly medication used for the treatment of GERD. The most widespread definition of Refractory GERD is the clinical condition that presents symptoms with partial or absent response to twice-daily PPI therapy. Persistence of symptoms occurs in 25% to 42% of patients who use PPI once-daily and in 10% to 20% who use PPI twice-daily. OBJECTIVE: The objective is to describe a review of the current literature, highlighting the causes, diagnostic aspects and therapeutic approach of the cases with suspected reflux symptoms and unresponsive to PPI. CONCLUSION: Initially, the management of PPI refractoriness consists in correcting low adherence to PPI therapy, adjusting the PPI dosage and emphasizing the recommendations on lifestyle modification change, avoiding food and activities that trigger symptoms. PPI decreases the number of episodes of acid reflux; however, the number of “non-acid” reflux increases and the patient continues to have reflux despite PPI. In this way, it is possible to greatly reduce greatly the occurrence of symptoms, especially those dependent on the acidity of the refluxed material. Response to PPI therapy can be evaluated through clinical, endoscopic, and reflux monitoring parameters. In the persistence of the symptoms and/or complications, other causes of Refractory GERD should be suspected. Then, diagnostic investigation must be initiated, which is supported by clinical parameters and complementary exams such as upper digestive endoscopy, esophageal manometry and ambulatory reflux monitoring (esophageal pH monitoring or esophageal impedance-pH monitoring). Causes of refractoriness to PPI therapy may be due to the true Refractory GERD, or even to other non-reflux diseases, which can generate symptoms similar to GERD. There are several causes contributing to PPI refractoriness, such as inappropriate use of the drug (lack of patient adherence to PPI therapy, inadequate dosage of PPI), residual acid reflux due to inadequate acid suppression, nocturnal acid escape, “non-acid” reflux, rapid metabolism of PPI, slow gastric emptying, and misdiagnosis of GERD. This is a common cause of failure of the clinical treatment and, in this case, the problem is not the treatment but the diagnosis. Causes of misdiagnosis of GERD are functional heartburn, achalasia, megaesophagus, eosinophilic esophagitis, other types of esophagitis, and other causes. The diagnosis and treatment are specific to each of these causes of refractoriness to clinical therapy with PPI.

Background:In children and young people (CYP) with JIA, we have previously identified clusters with different patterns of disease impact following methotrexate (MTX) initiation. It is unclear whether clusters of treatment response following etanercept (ETN) therapy exist and whether, in a group of CYP who have responded inadequately to or had adverse events on methotrexate, similar treatment response patterns exist. Novel response patterns would aid stratified treatment approaches through better understanding and potential forecasting of more specific response patterns across multiple domains of disease.Objectives:To identify and characterise trajectories of juvenile arthritis disease activity score (JADAS) components following ETN initiation for JIA.Methods:ETN-naïve CYP with non-systemic JIA were selected if enrolled prior to January 2019 in at least one of four CLUSTER consortium studies: BSPAR-ETN, BCRD, CAPS and CHARMS, at point of starting ETN as their first biological therapy. JADAS components (active joint count, physician’s global assessment (0-10cm), parental global evaluation (0-10cm) and standardised ESR (0-10) were collected at ETN initiation and during the following year.Multivariate group-based trajectory models, that identify clusters of CYP with similar patterns of change over time, were used to explore ETN response clusters across the different JADAS components. Censored-normal (global scores, ESR) and zero-inflated Poisson (active joint count) models were used, adjusting for year of ETN initiation. Optimal models were selected based on a combination of model fit (BIC), parsimony, and clinical plausibility.Results:Of the 1003 CYP included, the majority were female (70%) and of white ethnicity (90%), with rheumatoid factor-negative JIA the most common disease category (39%).The optimal model identified five trajectory clusters of disease activity following initiation of ETN (Figure 1). Clusters following ETN were similar and covered similar proportions of CYP to those previously identified following MTX: Fast (Group 1: 13%) and Slow (Group 2: 10%) response, active joint count improves but either physician (Group 3: 6%) or parent global scores (Group 4: 34%) remain persistently raised and a group with persistent raised scores across all JADAS components (Group 5: 36%). Compared to the persistent disease cluster, those with greater improvement had lower age and higher functional ability at ETN initiation and those with persistent raised parent global scores had lower ESR levels and were less likely to be RF-positive at ETN initiation.Figure 1.Clusters identified following ETN initiation in children and young people recruited to the UK BSPAR-ETN, BCRD, CAPS and CHARMS studies.Conclusion:This study has identified that within CYP initiating ETN, similar response clusters are evident to those previously identified following MTX. This commonality suggests a new framework for understanding treatment response, beyond a simple responder/non-responder analysis at a set point, which applies across multiple drugs despite different mechanisms of action and previous unfavourable treatment outcomes. Understanding both clinical factors associated with, and biological mechanisms underpinning, these clusters would aid stratified medicine in JIA.Acknowledgements:We thank the children, young people and families involved in CLUSTER, as well as clinical staff, administrators and data management teams. Funding for CLUSTER has been provided by generous grants from the MRC, Versus Arthritis, GOSH children’s charity, Olivia’s vision and the NIHR Manchester and GOSH BRC schemes.Disclosure of Interests:Stephanie Shoop-Worrall: None declared, Kimme Hyrich Speakers bureau: Abbvie, Grant/research support from: BMS, UCB, Pfizer, Lucy Wedderburn Speakers bureau: Pfizer, Grant/research support from: Abbvie, Sobi, Wendy Thomson Grant/research support from: Abbvie, Sobi, Nophar Geifman Grant/research support from: Abbvie, Sobi

1. This study focuses on the neural mechanisms underlying short-term adaptation of saccadic eye movements in the rhesus monkey. Involuntary saccades of various amplitudes and directions (E-saccades) were elicited in complete darkness by electrical stimulation (< or = 50 microA) in the deeper layers of the superior colliculus (SC) at 30 different sites in two monkeys. E-saccades at a given site could be adapted by presenting a visual target at a small distance from the expected end point immediately after their occurrence. The monkeys were trained to null the ensuing error signal by making the appropriate correction saccade to the visual target in many successive trials (E-adap paradigm). By properly adjusting the location of the visual target relative to the end point of the E-saccade, the latter could be modified in amplitude as well as in direction. 2. E-saccade modifications were highly significant, always in the intended direction, and occurred only if a postsaccadic visual error signal was created. These changes were plastic and required a subsequent E-adap series with an opposite error signal to cancel them. Their time course, both during the adaptation and the readaptation period, indicated that the modification was a slow and gradual process, as has been observed earlier in classical visual adaptation experiments. 3. Postadaptation tests, assessing whether the adaptation of E-saccades was also noticeable in normal visually guided saccades (V-saccades), showed incomplete adaptation transfer that was significant in most cases. A similar result, significant in all cases, was obtained with an extended version of the E-adap paradigm in which movement planning on the basis of target selection was possible. In this case, a presaccadic visual target was presented at the expected end point of the E-saccade, which was evoked just before the monkey would make a voluntary saccade itself (VE-adap). 4. In another series of experiments, V-saccades, which were matched to the optimal saccade vector of the particular collicular site under investigation, were adapted with the classical intrasaccadic target shift paradigm (V-adap). In agreement with earlier findings, this V-adaptation showed no transfer to the E-saccades. This result was obtained even in trials in which movement planning on the basis of target selection was possible (VE-test). 5. Our experiments have shown that saccades of collicular origin can be adapted and that presaccadic target selection is not crucial for this process. Both results are nicely in line with an existing model featuring a downstream adaptive corrector with access to SC inputs. This scheme, however, does not explain why the degree of saccadic adaptation, achieved by applying any of the three adaptation paradigms (E-adap, EV-adap, or V-adap), was never equally expressed in V- and E-saccades. Arguments for extending the model by adding a cortical input from the frontal eye fields to the adaptive corrector are discussed.

Abstract STUDY QUESTION Are progesterone (P) levels on the day before natural cycle frozen embryo transfer (NC-FET) associated with live birth rate (LBR)? SUMMARY ANSWER Regular ovulatory women undergoing NC-FET with serum P levels &lt;10 ng/ml on the day before blastocyst transfer have a significantly lower LBR than those with serum P levels &gt;10 ng/ml. WHAT IS KNOWN ALREADY The importance of serum P levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established. However, no study has analyzed the importance of serum P levels in patients undergoing FET under a true natural endometrial preparation cycle. STUDY DESIGN, SIZE, DURATION This was a retrospective cohort study including 294 frozen blastocyst transfers under natural cycle endometrial preparation at a university-affiliated fertility centre between January 2016 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients had regular menstrual cycles and underwent NC-FET with their own oocytes. Only patients who had undergone serum P measurement between 8 am and 11 am on the day before FET were included. Patients did not receive any external medication for endometrial preparation or luteal phase support. Patients were divided into two groups according to serum P levels below or above 10 ng/ml on the day before FET. Univariate analysis was carried out to describe and compare the cycle characteristics with reproductive outcomes. To evaluate the effect of P, a multivariable logistic model was fitted for each outcome after adjusting for confounding variables. MAIN RESULTS AND THE ROLE OF CHANCE Mean serum P levels on the day before FET were significantly higher in patients who had a live birth compared to those who did not (14.5 ± 7.0 vs 12.0 ± 6.6 ng/ml, 95% CI [0.83; 4.12]). The overall clinical pregnancy rate (CPR) and LBR were 42.9% and 35.4%, respectively. Patients in the higher P group (&gt;10 ng/ml) had a higher LBR (41.1% vs 25.7%: risk difference (RD) 15.4%, 95% CI [5; 26]) and CPR (48.6% vs 33.0%: RD 15.6%, 95% CI [4; 27]). Patients with higher serum P levels on the day before FET (63% of patients) had an improved LBR (odds ratio: 1.05; 95% CI [1.02; 1.09]). Women with serum P levels &lt;10 ng/ml on the day before FET (37% of patients) had significantly higher weights (62.5 ± 9.9 vs 58.1 ± 7.1 kg, 95% CI [1.92; 6.90]) and BMI (22.9 ± 3.6 vs 21.6 ± 2.7 kg/m2, 95% CI [0.42; 2.25]) compared to patients with P levels &gt;10 ng/ml. LIMITATIONS, REASONS FOR CAUTION The main limitation of our study is its retrospective design. Other potential limitations are the detection of LH surge through urine testing and the inclusion of patients who did and did not undergo preimplantation genetic testing for aneuploidies. The protocol used in our institution for monitoring NC-FET does not look for the onset of progesterone secretion by the corpus luteum, and a slow luteinisation process or delay of corpus luteum function cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS We provide evidence that a minimum serum P threshold (P &gt;10 ng/ml) might be required for improved reproductive outcomes in NC-FET. This result suggests that there are different mechanisms by which P is produced and/or distributed by each patient. This study also provides an excellent model to evaluate the impact of luteal phase defect through NC-FET. A prospective evaluation to assess whether P supplementation should be individualised according to patient’s needs is necessary to support our findings. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used, and there are no competing interests.

ABSTRACTA mechanism responsible for directed transport and molecular separation in a symmetric channel is proposed. We found that under the action of spatial harmonic oscillations of the channel, the system exhibits a directed transport in either direction, presenting multiple current reversals as the amplitude and/or frequency of the oscillations are varied. The particles of different masses may be forced to move with different velocities in the same or in the opposite directions by properly adjusting driving parameters. The directed transport can be produced in both directions even in the absence of thermal noise, the latter can speed up or slow down the transport depending on the system parameters.

This study investigates the influence of the fuel injection strategy on safety against flashback in a gas turbine model combustor with premixing of H2–air mixtures. The flashback propensity is quantified and the flashback mechanism is identified experimentally. The A2EV swirler concept exhibits a hollow, thick-walled conical structure with four tangential slots. Four fuel injector geometries were tested. One of them injects the fuel orthogonal to the air flow in the slots (jet-in-crossflow injector (JICI)). Three injector types introduce the fuel almost isokinetic to the air flow at the trailing edge of the swirler slots (trailing edge injector (TEI)). Velocity and mixing fields in mixing zone and combustion chamber in isothermal water flow were measured with high-speed particle image velocimetry (PIV) and high-speed laser-induced fluorescence (LIF). The flashback limit was determined under atmospheric pressure for three air mass flows and 673 K preheat temperature for H2–air mixtures. Flashback mechanism and trajectory of the flame tip during flashback were identified with two stereoscopically oriented intensified high-speed cameras observing the OH* radiation. We notice flashback in the core flow due to combustion-induced vortex breakdown (CIVB) and turbulent flame propagation (TFP) near the wall dependent on the injector type. The flashback resistance (FBR) defined as the ratio between a characteristic flow speed and a characteristic flame speed measures the direction of propagation of a turbulent flame in the flow field. Although CIVB cannot be predicted solely based on the FBR, its distribution gives evidence for CIVB-prone states. The fuel should be injected preferably isokinetic to the air flow along the entire trailing edge in order to reduce the RMS fluctuation of velocity and fuel concentration. The characteristic velocity in the entire cross section of the combustion chamber inlet should be at least twice the characteristic flame speed. The position of the stagnation point should be tuned to be located in the combustion chamber by adjusting the axial momentum. Those measures lead to safe operation with highly reactive fuels at high equivalence ratios.

: Depression is a mood disorder or affective disorder disease with depression as the main symptom. It has become a kind of mental disease that cannot be ignored in the world that seriously endangers human physical and mental health. Antidepressants commonly used in clinics generally have some defects including slow action, unremarkable effects and large side-effects. Therefore, there has a huge developing space for the research of new and effective therapeutic drugs to supplement or replace traditional drugs. Essential oil has obvious advantages in the treatment of depression and other emotional diseases, its aromatic odor can directly stimulate the olfactory nerves, and the lipophilic small- molecular compounds can cross the blood-brain barrier easily, to play its regulatory role of releasing of neurotransmitters and hormones related to depression, or adjusting the expression of brain-derived neurotrophic factor and proinflammatory cytokines. The pathogenesis of depression and the problems in traditional medication was illustrated, the research on the antidepressant effects and mechanism of essential oils in recent years was summarized and the antidepressant chemical components in plant essential oils were reviewed in this article. It could provide scientific basis for essential oil to be a new choice for relieving depression and treating depression.

Abstract Previous studies have demonstrated that sleep-breathing disorders, and especially obstructive sleep apnea (OSA), can be observed in patients with a higher risk of progression to Alzheimer’s disease (AD). Recent evidence indicates that cerebrospinal fluid (CSF) AD-biomarkers are associated with OSA. In this study, we investigated these associations in a sample of patients with mild cognitive impairment (MCI), a condition that is considered the first clinical phase of AD, when patients showed biomarkers consistent with AD pathology. A total of 57 patients (mean age = 66.19; SD = 7.13) with MCI were included in the study. An overnight polysomnography recording was used to assess objective sleep parameters (i.e. apnea/hypopnea index [AHI], total sleep time, sleep efficiency, sleep latency, arousal index, awakening, stage 1, 2, and slow-wave sleep and rapid eye movement sleep, periodic limb movement index, O2 saturation during sleep, and percentage of time O2 saturation &lt;90%). Phosphorylated-tau (P-tau), total-tau (T-tau), and amyloid-beta 42 (Aβ42) were measured in CSF. Unadjusted correlation analyses showed that a higher AHI (reflecting higher OSA severity) was related to higher P-tau and T-tau (both results remained significant after Bonferroni correction, p = 0.001). Importantly, these associations were observed even after adjusting for potential confounders (i.e. age, sex, body mass index, sleep medication, smoking, hypertension, and heart disease). Although more research is needed to establish a causal link, our findings provide evidence that OSA could be related to the pathophysiological mechanisms involved in neurodegeneration in MCI patients.

Abstract Background Urinary schistosomiasis and its severe complications, mainly bladder cancer, are scarce in non-endemic areas. The deficiency in knowledge and clinical experience of schistosomiasis may lead to inadequate management. Highlighting these topics may be of value, especially with the increased immigration from endemic low-/middle-income countries (LMIC) to non-endemic high-income countries (HIC). Schistosomiasis is a parasitic infection endemic in many low- and middle-income countries. It can affect various systems but is best known for its effect on the urinary system. Main Body PubMed, Scopus, Google Scholar, and the Cochrane Library databases were searched for urinary schistosomiasis and its related bladder cancer published from 1980 till 2020. Schistosoma haematobium (SH) infecting the urinary bladder was considered by the IARC as group 1 definitive biological carcinogenic agent. Several carcinogenic pathways have been postulated but the exact mechanism(s) are not defined yet. A more thorough understanding of the parasite life cycle was explored to help eradicate the infection especially for the immigrants from endemic areas. This may prevent or slow down the process of carcinogenesis that leads to Schistosoma-associated bladder cancer (SA-BC), which is usually, but not conclusively, squamous cell carcinoma. Treatment of SA-BC generally follows the same guidelines as urothelial Schistosoma-non-associated bladder cancer (SNA-BC) management; however, prospective trials to confirm and refine the treatment approach for SA-BC have been relatively limited. Conclusion The available data showed that despite some etiologic and carcinogenic differences, the oncologic outcomes are generally comparable for SA-BC and NSA-BC when adjusting for stage, risk status, and comorbidities.

ABSTRACT Escherichia coli populations undergo repeated replacement of parental genotypes with fitter variants deep in stationary phase. We isolated one such variant, which emerged after 3 weeks of maintaining an E. coli K-12 population in stationary phase. This variant displayed a small colony phenotype and slow growth and was able to outcompete its ancestor over a narrow time window in stationary phase. The variant also shows tolerance to beta-lactam antibiotics, though not previously exposed to the antibiotic. We show that an RpoC(A494V) mutation confers the slow growth and small colony phenotype on this variant. The ability of this mutation to confer a growth advantage in stationary phase depends on the availability of the stationary-phase sigma factor σS. The RpoC(A494V) mutation upregulates the σS regulon. As shown over 20 years ago, early in prolonged stationary phase, σS attenuation, but not complete loss of activity, confers a fitness advantage. Our study shows that later mutations enhance σS activity, either by mutating the gene for σS directly or via mutations such as RpoC(A494V). The balance between the activities of the housekeeping major sigma factor and σS sets up a trade-off between growth and stress tolerance, which is tuned repeatedly during prolonged stationary phase. IMPORTANCE An important general mechanism of a bacterium’s adaptation to its environment involves adjusting the balance between growing fast and tolerating stresses. One paradigm where this plays out is in prolonged stationary phase: early studies showed that attenuation, but not complete elimination, of the general stress response enables early adaptation of the bacterium E. coli to the conditions established about 10 days into stationary phase. We show here that this balance is not static and that it is tilted back in favor of the general stress response about 2 weeks later. This can be established by direct mutations in the master regulator of the general stress response or by mutations in the core RNA polymerase enzyme itself. These conditions can support the development of antibiotic tolerance although the bacterium is not exposed to the antibiotic. Further exploration of the growth-stress balance over the course of stationary phase will necessarily require a deeper understanding of the events in the extracellular milieu.

Based on previous feasibility study on one degree of freedom (1DOF) pneumatic active control of pneumatic springs, this paper presents procedures and results of a more realistic 3DOF active control of a pneumatic vibration isolation table. The 3DOF motion of the pneumatic table, consisting of heaving, rolling, and pitching, is controlled directly by adjusting air pressure in four pneumatic cylinders in a dynamic manner with pneumatic valves, without any external actuator such as an electromagnet or voice coil. The time delay control, which is a software chosen in this study, together with the hardware, i.e., the pneumatic actuator, is shown to be very powerful in enhancing the performance of vibration isolation for ground excitation as well as in settling time reduction for payload excitation through simulations and measurements on the 3DOF motion control system. New key results found in the experimental approach are that the pneumatic actuator shows a dynamic behavior of a second-order system, instead of a first-order system, which has been used in existing literatures so far, and that just feed-forward control of the pneumatic actuator by the second-order model can compensate for the inherently slow response characteristics of the pneumatic actuator very successfully. Effectiveness of the proposed active pneumatic control technique in the multi-input and multi-output system is shown via singular value decomposition analysis on the transmissibility matrix. Promising future of the proposed control and performance analysis technique is further discussed based on the results in the case of payload excitations as well.

ABSTRACTCoupling of the input power to a dielectric in a rectangular microwave cavity by using a compound iris having both inductive and capacitive slits, has been investigated. The compound iris is used in combination with a variable tuning plunger to maintain a resonant frequency of 2.45 GHz and minimize the reflected power. Under certain conditions, the compound iris has been observed to achieve an improved coupling of the input power, resulting in higher temperature of cylindrical 0.95 cm rods of silicon carbide (SiC) and alumina (A12O3). By placing the SiC perpendicular to the applied E field (with SiC enclosed in a porous insulation partially filling the applicator), coupling with the compound iris by adjusting both inductive and capacitive slits was achieved for a wide range of values compared to the use of a single pair of inductive slits. The coupling was more sensitive to a precise positioning of the single inductive slit. Such a difference was not observed for the case where the sample was placed parallel to the E field. In temperatures over 1600°C have been reached with a 600 W of power injected into the cavity. In tests with low loss alumina samples (99.8% pure) placed parallel to the E field, the compound iris permitted a greater coupling and higher temperature. The presence of alumina insulation had a significant effect in achieving higher temperatures, and occassionally preventing the initiation of arcing.

Sarah Phelps’s screenplay The Witness for the Prosecution (2016) does more than simply rekindle interest in Agatha Christie’s original short story; rather, it points to its salvation. My understanding of adaptation follows Armelle Blin-Rolland’s model, which refuses to privilege either the source or the adapted text, considering both instead to form part of a textual multiplicity. The relationship between the two resembles, for Blin-Rolland, a vortex. Thus, the meanderings of Phelps’s adapted text cause us to take stock and to read the original itself as loiterature (Chambers) and thus as a text that eschews self-coincidence, that offers more to the idle reader than an efficient delivery of truth. Christie’s text, in other words, if I may myself adapt a term from Walter Benjamin, has an inherent adaptability. Rather than simply conjuring its own adaptation in a virtual future, “The Witness for the Prosecution” contains, in an immediate pre-diegetic past, the original source of itself as adaptation. This source text is not an alternative solution, but runs parallel to the actual reading—appealing, almost subliminally, for readers to produce it; it also runs idly, however, and, unlike its hasty corollary, is content to wait to catch a distracted eye.Before shifting the focus more squarely from the 2016 adaptation to the original text (and its status as auto-adaptation), I should like to draw attention to the format of Phelps’s screenplay. As a mini-series, and thus an adaptation for television rather than a feature film, Phelps’s text presents something of a readerly paradox in and of itself. The series was originally aired by the BBC on two consecutive nights over the 2016 Christmas period (26 and 27 December). Thus, viewers were forced to pause for thought, but not over a week, which has traditionally been the cadence for episodes of television mini-series; instead, the 24-hour pause represented something of an extended intermission. For this reason, it is not clear whether the effect of the pause was to heighten anticipation, and thus to madden readers, or to enable them to take time out to review the case and to ask questions that the reader of the short story may not have time to ask. For, of course, the story is a short one, on the shorter side even by the standards of Christie’s shorter fiction. The mini-series does not present an abridged version, therefore, which is often the case for feature film adaptations; rather, it lengthens the story considerably. The whole experience is drawn out, not condensed. And yet, it is not clear whether this change of pace significantly alters the viewer/reader’s experience.I shall argue here that what it in fact does is to draw out elements of the source text that otherwise pass by unseen. Thus, whether or not the experience that one has of the television mini-series is loiterly per se, it certainly causes the reader who is aware of the short story to reread the latter and, I argue here, to see it as itself an adaptation, and further as an adaptation of itself. Lastly, it is perhaps worth reflecting that, after this initial airing of the mini-series on BBC television, The Witness for the Prosecution became available on DVD and for online streaming. In these formats, the hiatus of the episode break can readily be skipped. The binge-viewer has the ability to view in haste. In addition to erasing, to some degree at least, the difference between a feature film and a television series, such viewing practices recall the perceived generic differences between literature, with its descriptive passages and detours, and crime fiction, with its tendency to be highly plot-, and especially end-, driven. In either case therefore, to apprehend crime fiction in a loiterly fashion is a learned activity, a process that may seem somewhat counterintuitive, but one that Christie’s texts reflexively promote even as they ensnare the reader in the cleverness of their plots.The short story is famous for its twist in the tale: the person who appears the most likely murderer and who is tried for the crime turns out, in fact, to be guilty, much to the surprise of his solicitor, Mr Mayherne. Phelps’s adaptation, for its part, ends with the solicitor, John Mayhew (an alternative surname already used in Christie’s own adaptation for the stage in 1953), walking into the sea off the French coast, determined, or so it would appear, to take his own life, having been informed by his client’s partner that she has known all along that Leonard Vole was guilty. In addition to a new ending, the mini-series also receives a substantial new beginning: Leonard and Romaine receive a back-story; so too, over the course of the mini-series, does Mayhew himself. His determination to save Leonard is set against the death of his own son, who left to fight in the First World War despite being too young for service. Mayhew’s wife, we learn, has never forgiven him for the loss of her son. Saving the innocent Leonard is Mayhew’s way of redeeming himself. When he discovers that he has been duped and that he has saved a guilty man, the only atonement he can see is his own death.While Mayhew’s probity is made ambiguous by Phelps, Leonard and Romaine’s common back-story serves to some degree to explain, if not to justify, their callous behaviour. Phelps’s dramatic first scene shows a soldier drifting almost literally blindly across no-man’s land between the trenches of a First World War battlefield, taking cover from exploding shells and finding refuge in a crater where he finds his future partner Romaine. What is staged here is a looking back to the past, but not in the kind of nostalgic longing for times gone by associated with Christie; instead, Phelps points back to the trauma of war, in the light of which the present is to be survived and negotiated. In her introduction to the edition of the short story republished following the success of the mini-series, Phelps discusses her expectations when being commissioned to adapt Christie’s works, with which she claimed to be familiar without having previously read them. She labels Christie the “epitome of a particular nostalgia-laden Englishness” and mentions, for example, having to step out of the way of people queuing to see The Mousetrap in London’s West End (Christie v). In the light of such comments, it is tempting to see Phelps’s mini-series as a means of circumnavigating popular conceptions of Christie and combating this nostalgia for things past (not only better times, perhaps, but also better detective fiction).A vortical reading of The Witness for the Prosecution as multiplicity, however, in no way works against the original short story; in fact, rather than stepping around it, Phelps’s extended diegetic frame causes us to reflect on the way in which the story itself looks back, making room for, and even conjuring, an unseen pre-diegetic space. Thus, the battleground scene serves a reflexive end, not simply excusing Leonard and Romaine’s subsequent behaviour, but also graphically staging the textual no man’s land of adaptation—the space between the entrenched positions of two authorial powers. The bomb craters suggest both the violence done to the source text and the possibility for a new start and an end to the dominion of previous masters. Not only Leonard and Romaine, but Sarah Phelps, the reader, and even John Mayhew—who steps out of the shadows of Mr Mayherne—all escape the certainties of an era, an empire, and embrace a new future. My argument here is not simply that Christie benefits from the new beginning of another’s adaptation, but that she herself adapted what precedes Mr Mayherne’s first interview with Leonard Vole in her original text.In the story’s final revelation, Romaine opposes Mr Mayherne’s purchase on the truth to her own: he, she states, “thought [Leonard] was innocent”, whereas she “knew – he was guilty!” (29). This is the truth that Phelps’s adaptation appears to mitigate with its staging of extenuating circumstances and casting of Mr Mayherne as the ultimate victim of the story. I do not wish to argue here that Leonard Vole is innocent; rather, what I shall argue is that Romaine and generations of readers have misunderstood the dynamics of the narrative, for the fundamental binary at play is not “thinking versus knowing” but “knowing versus believing”. In this case, therefore, I almost, but not quite, agree with Phelps’s statement that “it’s not the truth that matters […] but performance” (Christie viii). While the text is very much a performance, it is one that serves to “screen” a truth in the Freudian sense, as well as in the cinematic one: the truth that is showcased in the last line of the story also hides another truth, which is, paradoxically, the same one. By revealing the truth in the form of Romaine’s victory, the text hides the fact that Mr Mayherne has known the truth from the very start, and indeed, before that. The story is a performance therefore, but a fetishistic one that points to the truth precisely in order to keep it just out of view. In this way, what Mr Mayhew knows to be true is neither stated explicitly nor entirely repressed; instead, it is disavowed, and what the short story performs is a screen memory.Read vortically, Christie’s and Phelps’s texts both displace the element that separates knowledge from belief, which, as Ellen Lee McCallum notes (xii), is desire. In Phelps’s adaptation, John Mayhew desires to save Leonard Vole in order to redeem his son’s death; in Christie’s text, Mr Mayherne desires to save Leonard in order to save the text. This is salvation as theorised by Shoshana Felman, who famously considered that Henry James’s The Turn of the Screw could only be saved from the critical binary of ghost story versus psychoanalytical tale by having its ambiguity preserved. If Phelps’s adaptation becomes something of a ghost story (it is, at least, a tale of people haunted by the past), Christie’s original text uses a psychoanalytic move to disavow its own psychoanalytical mechanics. Whereas detective fiction is typically end-oriented, with its focus on the ultimate revelation of truth, the psychoanalytic text locates truth in a pre-text. Thus, to save “The Witness for the Prosecution”, the reader must adopt a beginning-oriented lens and establish the original shape of its pre-diegetic revelation. This means loitering (and enacting that paradoxical mix of idle resistance advanced by Chambers) at that very point where the logics of detective fiction are seemingly designed to fast-track the reader’s pursuit of the ultimate solution. For, while reading to discover the ending is still promoted by the crime narrative here, a counter-logics of hesitation and retrospection always accompanies the reader’s progress forwards. If chances to meander down side-alleys are limited, given the brevity of the story, it is this double movement, this walking with a backwards gaze, with half an eye on the present and half on the past, that forces even that reader most pre-disposed to task-focused digestion of the text to slow down and to wander. What is so striking in “The Witness for the Prosecution” is arguably how Christie makes space for wandering in such a restricted narrative, in a creative format that is, of course, all about punch and economy.This space is created as early as the story’s opening sentence. “Mr Mayherne”, it begins, “adjusted his pince-nez and cleared his throat with a little dry-as-dust cough that was wholly typical of him” (1). Whether or not we can be sure that Mr Mayherne’s cough was typical of him before the story begins is uncertain. His habit of adjusting his pince-nez, on the other hand, which is here associated with the cough, is certainly recently acquired. This we learn at the end of the story: “He found himself polishing his pince-nez vigorously, and checked himself. His wife had told him only the night before that he was getting a habit of it” (27). It is my contention that this habit is a response to a traumatic revelation of truth, which requires Mr Mayherne henceforth to adjust his perspective.Habits, as Mr Mayherne’s wife points out, are born of repetition. The story, too, begins with a repeated act. Indeed, the solicitor’s next action is to look at his client, whom the reader is seeing for the first time at this initial point of the text, but whom Mr Mayherne has already seen: “Then he looked again at the man opposite him” (1, my emphasis). At the outset therefore, this habit of adjusting his pince-nez is proleptic, insofar as it will enable him to realise (albeit apparently, but only apparently, too late) that Romaine and the old woman who gives him the letters that condemn her are one and the same, but also analeptic, as it looks back to a previous contemplation of a disguise. The habit that he detects in Romaine is one of clenching and unclenching her right hand. That he sees this without initially being fully conscious of it and then later understands the gesture’s significance is due to his own fetishistic response to the truth of Leonard’s guilt. When he first sees his client, he recognises his guilt, either in his eyes, which then causes him to avert his gaze and look down to his hands, or in his murderer’s hands, which causes him to displace his gaze and to look instead at his own hands, which he occupies by adjusting his pince-nez. Either way, his failure to look at Romaine’s hands and see them immediately for what they are is itself a displacement of his dual state—of knowing his client to be guilty and believing in his innocence “in spite of the multitude of facts arrayed against [him]” (13).Repetition blunts the reader’s awareness of its fundamental role in the story. The weight of evidence against Leonard Vole is repeated again and again. This is one of the key devices, even a cliché, of detective fiction: the most obviously guilty character must be innocent. At its most basic level, this is how “The Witness for the Prosecution” surprises its readers. My suggestion, however, is that this knowledge serves merely to screen the book’s original, or other, meaning, which is that Mr Mayherne knows the truth. It is not truth, but the knowledge of the truth, that the reader is tasked to discover. To this extent, Phelps is right: “it is not the truth that matters, but performance”. And in this case, it is the performance of the truth of Leonard’s guilt in the actualised story that hides the knowledge of the truth that is its pre-text and whose form is not taken by the story while nonetheless being analeptically staged and virtually formed, or (auto-)adapted, as pre-text. In reflexive terms, the highlighting of repeated gestures, and especially Mr Mayherne’s cleaning of his lenses, can usefully be considered signals for the reader to pause for thought. And yet, as reflexive signals, they are both provocative and provocatively hesitant, for however clearly they are displayed, they fail to check the pace and end-orientation of the short story because the reader’s own habit—the compulsion to read in haste, to read for the solution—is not so easily broken.Leonard’s first words in the story are simply, “I know”, which is, in the framework of the present reading, a pure reflection of what the man sitting opposite him is trying to disavow. What Leonard knows is that his situation is grave and that he must be frank. He knows this because, as he says to Mr Mayherne, “You keep telling me so” (1). But it is this response that in fact causes the story to become a tale of repetition. First, there is Mr Mayherne’s conviction: “we shall succeed—we shall succeed” (2). Romaine then repeats her desire when she first meets Mr Mayherne, twice stating the words, “I want to know the worst” (14). Leonard is nonetheless responding to a prior repetition, which, is predicated on the story’s initial “looking again”. In other words, the story itself is a screen memory, a fetish-made-diegesis. The result, in an apparent paradox, is that the desire to hasten the ending, to bring on the final verdict, however terrible, is at the same time a signal for the reader to look back. Again, to look back to that initial second look is to inscribe circles on circles, and to enforce wandering even at this reflexively-staged moment of end-orientation.Certainly, Romaine’s comment, “I want to know”, performs fetishism’s combination of knowledge and desire. And yet, unlike Mr Mayherne’s desire (to save Leonard), which is opposed to his knowledge (that Leonard is guilty), Romaine’s desire appears aligned with knowledge: she does not say that she knows the worst, but that she wants to know it. She has another secret desire, of course, as she reveals to Mr Mayherne in what is a paradoxical display of secrecy. When he asks why she hates her husband so much, she retorts: “Yes, you would like to know. But I shall not tell you. I will keep my secret” (17). Further, she mocks him for honestly believing Leonard to be innocent.Both characters are honest, then: Romaine wants to know that Leonard is guilty (and certainly does not believe him to be innocent) and openly has a secret that she will not divulge; Mr Mayherne, for his part, knows the case against his client is ironclad but also honestly believes him to be innocent. Their stated aims may well be opposed—she wants Leonard to hang; he wants him to go free. Their “true” aims are nonetheless aligned: she knows Leonard is guilty and will sacrifice her own credibility in court to save her husband; he believes Leonard is innocent and will sacrifice her in court to save his client. Both tell the truth in public when performing their official duties (he as solicitor, she as wife). The only difference between them lies in the nature of their other performance: she lies to him by performing the role of an old woman who knows secrets about her past; he knows Leonard to be guilty but partially represses this by taking up his narrative only after he has erected a fetish to protect himself from this traumatic truth (and the reader from the secret past of the text). This disavowal means that he can honestly believe in his client’s innocence while still knowing him to be guilty. Again then, Phelps’s statement—that it is not the truth that matters, but performance—is itself both true and not true. Romaine performs in the story in order for the truth that she knows to be said and then discredited; Mr Mayherne, on the other hand, performs the story in order for his knowledge of the truth to be disavowed, which it to say, repressed within the form that is given to the reader to see, but also available, and able to take form (for the reader prepared to digress) in what lies just beyond the limits of what is said.The conversation in which Romaine repeats her desire to know also ends in a repetition, this time with one of the solicitor’s signature moves: “Mr Mayherne gave his dry little cough and rose” (17). This cough repeats the one that opened the story. In that first instance, it distracted the reader, allowing the adverb “again” to rush through, seen and unseen. In this way, the first cough, accompanied by Mr Mayherne’s cleaning of his lenses, causes the reader to focus their own gaze on him rather than on what he had been looking at. This is a cough designed to open the narrative on Mr Mayherne’s terms. In this second example, it closes down dialogue. This second cough is motivated by precisely the same traumatic revelation of the truth, except that in this repetition it is displaced onto Romaine. With the words, “I shall not tell you. I will keep my secret”, she says to him in the text what Mr Mayherne said to himself in the pre-text. This is a repetition therefore in a story of repetition and of a story of repetition. Repeating what was said before with different words and, at the same time, repeating with the same words what was not said before, the text here presents itself to the reader in the form of an auto-adaptation, a second look at an original text whose form is otherwise virtual.In this way, words unsaid are repressed partially: they are not said in the diegesis (which stands as a screen memory, simultaneously standing in place of the text and tracing in the present the contours of its form as absence) but are said, instead, by proxy, through displacement, in the reflexively staged performance of another text. The disavowal at play here is such that readers find themselves in two spaces at once, on two lines of flight, with the one being opposed to the other. Steps forwards and backwards are taken in equal measure. We are therefore witnesses to “The Witness for the Prosecution”, looking on as the story follows onwards, but this very act of witnessing counteracts this prosecution, adding the idleness of the gaze to the purposefulness of pursuit (of truth). The result is not so much somewhere between a stalled, or false, start, and a race to the end, as both at the same time. In this way, Christie’s story, despite appearances to the contrary, is the very embodiment of wandering.At the origins of both Christie’s story and Phelps’s adaptation is a common truth. It serves as a pre-text for both texts, for both performances. In both cases, this pre-text privileges performance over truth. Each text also has a pre-text, which precedes and predicates the performance. We may consider that Phelps’s adaptation captures the essence (of truth) of Christie’s original. In this way, it values that truth and holds it necessary to its own performance, without being derivative in relation to it. Again, the same holds for Christie’s text, whose pre-text protects its truth beneath its performance: while the performance partially represses this pre-textual truth (with its gaudy staging of its own truth, which we may perhaps this time consider derivative), it also preserves it. For without the performance (of truth), the knowledge at its origin cannot exist. To read “The Witness for the Prosecution” as an adaptation of itself requires a fetishistic eye, and the fetishist is nothing if not a digressive observer. If you’re quick, you can catch the performance; but if you’re content to wander, the audacity of what Christie does not reveal is well worth the wait.ReferencesBlin-Rolland, Armelle. “Adaplastics: Forming the Zazie dans le métro Network.” Modern and Contemporary France (2019): forthcoming.Chambers, Ross. Loiterature. Lincoln and London: University of Nebraska Press, 1999.Christie, Agatha. The Witness for the Prosecution and Other Stories. London: Harper, 2016.Felman, Shoshana. “Turning the Screw of Interpretation.” Yale French Studies. 55–56 (1977): 94–207.McCallum, Ellen Lee. Object Lessons: How to Do Things with Fetishism. New York: SUNY Press, 1992.The Witness for the Prosecution. Dir. Julian Jarrold. BBC One, 2016.