Reliable Triggering Research Articles

Design of reliable and fast Schmitt trigger 10T SRAM cells using in-memory computing

Abstract Microprocessors, integrated data storage systems, and cache memories are just a few applications that can benefit from Static random access memory (SRAM). Computing In memory provides a solution for the von Neumann bottleneck problems. Simultaneously, it removes needless repeated data transmission between CPU and memory. Schmitt trigger was utilized for energy-efficient operation to get high reading and writing capacity. Two cross-coupled inverters with a transistor in between increase the design writing process. Furthermore, voltage boost logic is prioritized to maximize the node capacity. Using two dummy columns and dummy rows in RAM, the Replica technique controls the flow of signals via the core. The simulated results are compared to the designs that already exist. The simulation results show that the leakage power of the proposed design is 0.75 nw at 0.6 volts. The write static noise margin (WSNM) of the proposed cell is twice that of SEDF10T, which can be helpful for high-performance computing applications.

P-614 The use of home ovulation prediction kits (OPKs) in true natural cycle frozen embryo transfer (NC FET)

Abstract Study question Do urinary OPKs have inferior ability to detect the LH surge compared to daily serum monitoring among patients undergoing true NC FET? Summary answer OPKs are highly accurate and may serve as reliable tests to detect the LH surge among patients undergoing NC FET. What is known already Frozen embryo transfers continue to increase worldwide and recent evidence suggests natural cycle protocols may be superior to hormone replacement protocols because of lower risk of miscarriage and lower risk of pregnancy complications. Patients undergoing NC FET attend multiple clinic appointments which has been associated with increased patient stress levels during fertility treatment. OPKs have been found to be accurate at detecting the LH surge in the trying to conceive population and have high user acceptability. Study design, size, duration A prospective single cohort study including 139 fertility seeking participants was completed at an academic-affiliated fertility center for a duration of 12 months. Participants/materials, setting, methods Patients scheduled for NC FET (regular cycles 27-35 days, mid luteal progesterone >30 nmol/L, no luteal phase concern) with the ability to provide informed consent and access to SMS texting devices were eligible for participation. On the same day they started daily morning bloodwork as per the standard protocol (2-3 days prior to anticipated LH surge), participants began twice daily OPK testing. Upon exiting the study, patients completed a questionnaire on satisfaction with OPK use. Main results and the role of chance LH surge detection rate was 85.6% (n = 119/139) with serum monitoring and 93.5% (130/139) with OPK use (Kappa agreement 90.7%, K = 0.51, p < 0.001). Among patients with a serum-detected LH surge, OPK was positive within +/- 12 hours of the serum LH surge detection in 84.8% of patients. In 23.7% of cycles, OPK was positive the same morning as serum blood work. In 27.1% of cycles, OPK was positive 12h prior and in 33.9% of cycles, OPK was positive 12h after serum LH surge detection. Actual NC FET cycle cancellation rate was 16.6% (n = 23/139) compared to an anticipated cycle cancellation rate of 20.9% (29/139) if OPKs had been used to initiate serum monitoring. The average reduction in the number of serum monitoring visits and distance travelled in kilometers with OPK use was 3.9 visits (SD 2.1) and 155km (SD 174), respectively. The majority of participants reported satisfaction with OPK use. Of 135 patients, 110 (81.5%) strongly agreed the OPK was easy to use, 100 (74.1%) strongly agreed they would be open to using OPKs in future fertility treatments and 120 (88.9%) reported a reduction or no impact on stress levels associated with fertility treatments. Limitations, reasons for caution This study only used Clearblue Digital Ovulation Tests and the reported reliability in our study cannot be extrapolated to all OPKs. Additionally, the accuracy of the reported serum LH surge detection rate may be limited by physician specific definitions of serum LH surge. Wider implications of the findings OPKs are highly accurate and may serve as a reliable trigger for serum monitoring in NC FET. While their use would reduce the number of clinic appointments and distance travelled for patients undergoing NC FET cycles, patients should be advised OPK use may be associated with higher cycle cancellation rates. Trial registration number Not applicable

Characterization of an Algorithm for Autonomous, Closed-Loop Neuromodulation During Motor Rehabilitation

Background Recent evidence demonstrates that manually triggered vagus nerve stimulation (VNS) combined with rehabilitation leads to increased recovery of upper limb motor function after stroke. This approach is premised on studies demonstrating that the timing of stimulation relative to movements is a key determinant in the effectiveness of this approach. Objective The overall goal of the study was to identify an algorithm that could be used to automatically trigger VNS on the best movements during rehabilitative exercises while maintaining a desired interval between stimulations to reduce the burden of manual stimulation triggering. Methods To develop the algorithm, we analyzed movement data collected from patients with a history of neurological injury. We applied 3 different algorithms to the signal, analyzed their triggering choices, and then validated the best algorithm by comparing triggering choices to those selected by a therapist delivering VNS therapy. Results The dynamic algorithm triggered above the 95th percentile of maximum movement at a rate of 5.09 (interquartile range [IQR] = 0.74) triggers per minute. The periodic algorithm produces stimulation at set intervals but low movement selectivity (34.05%, IQR = 7.47), while the static threshold algorithm produces long interstimulus intervals (27.16 ± 2.01 seconds) with selectivity of 64.49% (IQR = 25.38). On average, the dynamic algorithm selects movements that are 54 ± 3% larger than therapist-selected movements. Conclusions This study shows that a dynamic algorithm is an effective strategy to trigger VNS during the best movements at a reliable triggering rate.

Magilock: a reliable control triggering method in multi-channel eye-control systems.

Eye-tracking technology brings a different human-computer interaction experience to users because of its intuitive, natural, and hands-free operation characteristics. Avoiding the Midas touch problem and improving the accuracy of interaction are among the main goals of the research and development of eye-control systems. This study reviews the methods and limitations of research on avoiding the Midas touch problem. For typical control clicking operations with low fault tolerance, such as mode switching and state selection in an eye-control system, this study proposes Magilock, a more reliable control triggering method with a high success rate in multi-channel eye-control systems. Magilock adds a control pre-locked mechanism between the two interactive steps of eye-control channel positioning control and other interactive channel triggering controls in the multi-channel eye-control system. This effectively avoids incorrect control triggering caused by multi-channel coordination disorder and gaze-point drift. This study also conducted ergonomic experiments to explore the lock and unlock times of the control pre-locked mechanism in Magilock. Taking into account the experimental data and subjective evaluation of the participants, we recommend setting the lock time and the unlock time of Magilock to 200 ms.

Distributed Fixed-Time Leader-Following Consensus for Multi-Agent Systems: An Event-Triggered Mechanism

In this work, a fixed-time leader-following event-triggered (ET) consensus problem for multi-agent systems (MASs) with external disturbances is investigated. A distributed observer is developed to achieve the estimated state of the leader. By means of the observation information, the consensus error system for multi-agents is reformulated into a tracking error system, wherein individual follower agent aims to track the leader agent. Building upon Lyapunov technology and fixed-time stability theory, a new ET protocol is introduced to mitigate communication wastes. Notably, the proposed controller incorporates a strong robust fixed-time control form with lower complexity, and a reliable dynamic triggering condition also ensures the excellent performance of the system. Rigorous demonstrations underscore the stability and robustness of the ET method, while guaranteeing the avoidance of Zeno behavior. Finally, several numerical simulations are provided to underscore the efficacy of the proposed protocols.

Active monitoring of antifungal adverse events in hospitalized patients based on Global Trigger Tool method.

The increasing prevalence of fungal infections necessitates broader use of antifungal medications. However, the prevalence of adverse drug events (ADEs) restricts their clinical application. This study aimed to develop a reliable ADEs trigger for antifungals to enable proactive ADEs monitoring, serving as a reference for ADEs prevention and control. This investigation comprises two phases. Initially, the trigger was established via a literature review, extraction of relevant items, and refinement through Delphi expert consultation. Subsequently, the validity of the trigger was assessed by analyzing hospital records of antifungal drug users from 1 January 2019 to 31 December 2020. The correlation between each trigger signal and ADEs occurrence was examined, and the sensitivity and specificity of the trigger were evaluated through the spontaneous reporting system (SRS) and Global Trigger Tool (GTT). Additionally, risk factors contributing to adverse drug events (ADEs) resulting from antifungal use were analyzed. Results: Twenty-one preliminary triggers were refined into 21 final triggers after one expert round. In the retrospective analysis, the positive trigger rate was 65.83%, with a positive predictive value (PPV) of 28.75%. The incidence of ADEs in inpatients was 28.75%, equating to 44.58 ADEs per 100 admissions and 33.04 ADEs per 1,000 patient days. Predominant ADEs categories included metabolic disturbances, gastrointestinal damage, and skin rashes. ADEs severity was classified into 36 cases at grade 1, 160 at grade 2, and 18 at grade 3. The likelihood of ADEs increased with longer stays, more positive triggers, and greater comorbidity counts. This study underscores the effectiveness of the GTT in enhancing ADEs detection during antifungal medication use, thereby confirming its value as a monitoring tool.

Triggers for freezing of gait in individuals with Parkinson's disease: a systematic review.

Freezing of Gait (FOG) is a motor symptom frequently observed in advanced Parkinson's disease. However, due to its paroxysmal nature and diverse presentation, assessing FOG in a clinical setting can be challenging. Before FOG can be fully investigated, it is critical that a reliable experimental setting is established in which FOG can be evoked in a standardized manner, but the efficacy of various gait tasks and triggers for eliciting FOG remains unclear. This study aimed to conduct a systematic review of the existing literature and evaluate the available evidence for the relationship between specific motor tasks, triggers, and FOG episodes in individuals with Parkinson's disease (PwPD). We conducted a literature search on four online databases (PubMed, Web of Science, EMBASE, and Cochrane Library) using the keywords "Parkinson's disease," "Freezing of Gait", "triggers" and "tasks". A total of 128 articles met the inclusion criteria and were included in our analysis. The review found that a wide range of gait tasks were employed in studies assessing FOG among PD patients. However, three tasks (turning, dual tasking, and straight walking) emerged as the most frequently used. Turning (28%) appears to be the most effective trigger for eliciting FOG in PwPD, followed by walking through a doorway (14%) and dual tasking (10%). This review thereby supports the utilisation of turning, especially a 360-degree turn, as a reliable trigger for FOG in PwPD. This finding could be beneficial to clinicians conducting clinical evaluations and researchers aiming to assess FOG in a laboratory environment.

A neutron trigger detector for pulsed reactor neutron sources

A variety of experiments investigating properties of neutrons can be performed at pulsed reactor neutron sources like the research reactor TRIGA Mainz. A typical problem faced by these experiments is the non-availability of a reliable facility-provided trigger signal in coincidence with the neutron production. Here we present the design and implementation of a neutron pulse detector that provides a coincident trigger signal for experimental timing with a relative precision of 4.5ms.

-Memory Computing Based Reliable and High Speed Schmitt trigger 10T SRAM cell design

Static random access memories (SRAM) are useful building blocks in various applications, including cache memories, integrated data storage systems, and microprocessors. The von Neumann bottleneck difficulties are solved by in-memory computing. It eliminates unnecessary frequent data transfer between memory and processing units simultaneously. In this research, the replica-based 10T SRAM design for in-memory computing (IMC) is designed by adapting the word line control scheme in 14nm CMOS technology. In order to achieve high reading and writing capability, the Schmitt trigger inverter was used for energy-saving and stable use. To speed up the writing process of the design, a single transistor is inserted between the cross-coupled inverters. In addition, to increase the node capacity, the voltage boosting circuitry is emphasized. The adaptive word line control scheme was utilized by integrating the replica column based circuit. The Replica approach regulates signal flow through the core by using a dummy column and a dummy row in RAM. To demonstrate the viability of the suggested design, the simulated outcomes are contrasted with those of existing designs. The various performance metrics examined are Read Static Noise Margin (RSNM), Write (WSNM), Hold (HSNM), Read Access Delay (RAD), Write Access Delay (WAD), Read performance and Write performance the varying supply voltage is evaluated.

Assessment of oxygen extraction rate changes following red blood cell transfusion in the intensive care unit: a protocol for a prospective observational non-interventional study

IntroductionHaemoglobin transfusion thresholds have been used in the intensive care unit (ICU) to guide red blood cell transfusion (RBCT) decisions. Recent research has also focused on physiological indicators of tissue...

Air Medical Blood Transfusion as a Trigger of Massive Transfusion Protocol

Air medical services can improve access to blood products at the point of injury. Studies have shown that early activation of mass transfusion protocols (MTPs) can improve the survival of trauma patients by up to 25%. There are several scoring systems to guide early activation, but the use of a single criterion has been elusive. Our study sought to determine if air medical administration of blood products was a risk factor for massive transfusion activation and utilization of prehospital vital signs for calculation of the shock index. In our retrospective study, we evaluated adult trauma patients transfused by helicopter emergency medical services (HEMS) and as a control all patients in our institution receiving the MTP. Our study found HEMS blood transfusion was not a reliable trigger for MTP, although the sample size may have limited our findings. We found that HEMS care resulted in an overall reduction in the volume of transfusion and an improvement in hemodynamic parameters upon trauma center arrival. HEMS transfusion and a higher rate of tranexamic acid administration may have contributed to these findings. Of note, the assessment of blood consumption score and shock index were nonspecific in the study populations.

Peripheral CCL2-CCR2 signalling contributes to chronic headache-related sensitization.

Migraine, especially chronic migraine, is highly debilitating and still lacks effective treatment. The persistent headache arises from activation and sensitization of primary afferent neurons in the trigeminovascular pathway, but the underlying mechanisms remain incompletely understood. Animal studies indicate that signalling through chemokine C-C motif ligand 2 (CCL2) and C-C motif chemokine receptor 2 (CCR2) mediates the development of chronic pain after tissue or nerve injury. Some migraine patients had elevated CCL2 levels in CSF or cranial periosteum. However, whether the CCL2-CCR2 signalling pathway contributes to chronic migraine is not clear. Here, we modelled chronic headache with repeated administration of nitroglycerin (NTG, a reliable migraine trigger in migraineurs) and found that both Ccl2 and Ccr2 mRNA were upregulated in dura and trigeminal ganglion (TG) tissues that are implicated in migraine pathophysiology. In Ccl2 and Ccr2 global knockout mice, repeated NTG administration did not evoke acute or persistent facial skin hypersensitivity as in wild-type mice. Intraperitoneal injection of CCL2 neutralizing antibodies inhibited chronic headache-related behaviours induced by repeated NTG administration and repetitive restraint stress, suggesting that the peripheral CCL2-CCR2 signalling mediates headache chronification. We found that CCL2 was mainly expressed in TG neurons and cells associated with dura blood vessels, whereas CCR2 was expressed in subsets of macrophages and T cells in TG and dura but not in TG neurons under both control and disease states. Deletion of Ccr2 gene in primary afferent neurons did not alter NTG-induced sensitization, but eliminating CCR2 expression in either T cells or myeloid cells abolished NTG-induced behaviours, indicating that both CCL2-CCR2 signalling in T cells and macrophages are required to establish chronic headache-related sensitization. At cellular level, repeated NTG administration increased the number of TG neurons that responded to calcitonin-gene-related peptide (CGRP) and pituitary adenylate cyclase activating polypeptide (PACAP) as well as the production of CGRP in wild-type but not Ccr2 global knockout mice. Lastly, co-administration of CCL2 and CGRP neutralizing antibodies was more effective in reversing NTG-induced behaviours than individual antibodies. Taken together, these results suggest that migraine triggers activate CCL2-CCR2 signalling in macrophages and T cells. This consequently enhances both CGRP and PACAP signalling in TG neurons, ultimately leading to persistent neuronal sensitization underlying chronic headache. Our work not only identifies the peripheral CCL2 and CCR2 as potential targets for chronic migraine therapy, but also provides proof-of-concept that inhibition of both peripheral CGRP and CCL2-CCR2 signalling is more effective than targeting either pathway alone.

Improved Marx Pulse Generator With Auxiliary Trigger Topology (2022)

Marx multi-stage circuits based on avalanche transistors are widely used in high-power nanosecond pulse applications. In response to the low reliability of the conventional Marx circuit, this paper analyzed the corresponding failure mechanism and discovered that the conduction modes were the main cause of failure. Based on this, a new topology is designed, by changing the conduction mode from "overvoltage switching-on" to "triggering switching-on". The simulation and measurement results show that the new structure has the advantages of high efficiency, stable operation, low output delay and short output pulse front. Meanwhile, to further improve the output efficiency,= a multiplexed stacking solution is designed based on the new structure, and the simulation results show that the output efficiency is up to 95%. The research in this paper can provide solutions for accurate and reliable synchronous triggering of key units such as gas switches in pulsed power systems, and also provide references for the design of high-efficiency nanosecond pulse generators.

Expert consensus established around flexible, individualized migraine treatment utilizing a modified Delphi panel.

To characterize treatment decision-making processes and formalize consensus regarding key factors headache specialists consider in treatment decisions for patients with migraine, considering novel therapies. Migraine therapies have long been subject to binary classification, acute versus preventive, due to limitations of available drugs. The emergence of novel therapies that can be used more flexibly creates an opportunity to rethink this binary classification. To determine the role of these novel therapies in treatment, it is critical to understand whether existing guidelines reflect clinical practice and to establish consensus around factors driving management. A three-round modified Delphi process was conducted with migraine clinical experts. Round 1 consisted of an online questionnaire; Round 2 involved an online discussion of aggregated Round 1 results; and Round 3 allowed participants to revise Round 1 responses, incorporating Round 2 insights. Questions elicited likelihood ratings (0= highly unlikely to 100=highly likely), rankings, and estimates on treatment decision-making. Nineteen experts completed three Delphi rounds. Experts strongly agreed on definitions for "acute" (median= 100, inter-quartile range [IQR]=5) and "preventive" treatment (median=90, IQR=15), but noted a need for treatment customization for patients (median=100, IQR=6). Experts noted certain aspects of guidelines may no longer apply based on established tolerability and efficacy of newer acute and preventive agents (median=91, IQR=17). Further, experts agreed on a treatment category referred to as "situational prevention" (or "short-term prevention") for patients with reliable and predictable migraine triggers (median=100, IQR=10) or time-limited periods when headache avoidance is important (median=100, IQR=12). Using the modified Delphi method, a panel of migraine experts identified the importance of customizing treatment for people with migraine and the utility of "situational prevention," given the ability of new treatment options to meet this need and the potential to clinically identify patients and time periods when this approach would add value.

Peroxynitrite Contributes to Behavioral Responses, Increased Trigeminal Excitability, and Changes in Mitochondrial Function in a Preclinical Model of Migraine.

Administration of a nitric oxide (NO) donor triggers migraine attacks, but the mechanisms by which this occurs are unknown. Reactive nitroxidative species, including NO and peroxynitrite (PN), have been implicated in nociceptive sensitization, and neutralizing PN is antinociceptive. We determined whether PN contributes to nociceptive responses in two distinct models of migraine headache. Female and male mice were subjected to 3 consecutive days of restraint stress or to dural stimulation with the proinflammatory cytokine interleukin-6. Following resolution of the initial poststimulus behavioral responses, animals were tested for hyperalgesic priming using a normally non-noxious dose of the NO donor sodium nitroprusside (SNP) or dural pH 7.0, respectively. We measured periorbital von Frey and grimace responses in both models and measured stress-induced changes in 3-nitrotyrosine (3-NT) expression (a marker for PN activity) and trigeminal ganglia (TGs) mitochondrial function. Additionally, we recorded the neuronal activity of TGs in response to the PN generator SIN-1 [5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride]. We then tested the effects of the PN decomposition catalysts Fe(III)5,10,15,20-tetrakis(N-methylpyridinium-4-yl) porphyrin (FeTMPyP) and FeTPPS [Fe(III)5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato chloride], or the PN scavenger MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin] against these behavioral, molecular, and neuronal changes. Neutralizing PN attenuated stress-induced periorbital hypersensitivity and priming to SNP, with no effect on priming to dural pH 7.0. These compounds also prevented stress-induced increases in 3-NT expression in both the TGs and dura mater, and attenuated TG neuronal hyperexcitability caused by SIN-1. Surprisingly, FeTMPyP attenuated changes in TG mitochondrial function caused by SNP in stressed males only. Together, these data strongly implicate PN in migraine mechanisms and highlight the therapeutic potential of targeting PN.SIGNIFICANCE STATEMENT Among the most reliable experimental triggers of migraine are nitric oxide donors. The mechanisms by which nitric oxide triggers attacks are unclear but may be because of reactive nitroxidative species such as peroxynitrite. Using mouse models of migraine headache, we show that peroxynitrite-modulating compounds attenuate behavioral, neuronal, and molecular changes caused by repeated stress and nitric oxide donors (two of the most common triggers of migraine in humans). Additionally, our results show a sex-specific regulation of mitochondrial function by peroxynitrite following stress, providing novel insight into the ways in which peroxynitrite may contribute to migraine-related mechanisms. Critically, our data underscore the potential in targeting peroxynitrite formation as a novel therapeutic for the treatment of migraine headache.

A novel method of hybrid plasma injection driven by the pulsed discharge of a metal-polytetrafluoroethylene-stacked capillary in high-pressure SF6.

A reliable and repeatable triggering technology for a megavolt gap switch with a low working coefficient η is an urgent need and a research focus. In this study, a novel method of hybrid plasma injection (HPI) driven by pulsed discharge inside a capillary was first proposed. The HPI actuator adopted a metal-polytetrafluoroethylene (PTFE)-stacked capillary, in which severe ablation could generate a hybrid plasma containing gas and metal vapor ionized component ejected outward from the nozzle. The HPI actuator could perform repeatedly with an extremely strong plasma injection and triggering ability and, thus, provided a solution for megavolt ultrafast bypass switches (UFBPSs). The evolution and the trigger properties of the HPI actuator were investigated, and the influence of the stacked material (Al, Zn, and Sn) and its proportion (3/15, 7/15, and 10/15) was studied, followed by the performance degradation in multi-shot. It was found that stacking chemically active and low-ionization-energy aluminum in a proportion of 7/15 strongly enhanced the HPI, with an initial velocity of 1200m/s and a maximum height of 7.5cm in 0.5 MPa SF6. In repeated operations, the HPI actuator performance degraded obviously due to capillary expansion and deformation, and the lifetime was tens of magnitude. Finally, the optimized HPI actuator was used to trigger a 7 cm-0.5 MPa SF6 gap, with a breakdown voltage of ∼1.5 MV. When a 100kV DC voltage was applied (η < 7%), the gap was successfully and continuously triggered for 27 shots with the trigger delay ranging from 301 to 670 µs, indicating that the HPI actuator could effectively and repeatedly trigger megavolt-magnitude SF6 gaps at a very low η and was a good solution for megavolt UFBPSs.

Trigger Properties of an Ejected-Plasma-Triggered SF Gas Gap for 10-kV Smart Distribution Network

Aimed at developing a rapid control and protection switch for a 10-kV smart distribution network, a gas switch triggered by ejected plasma was designed and tested. The switch met the requirements of fast and reliable triggering at an extremely low operating coefficient. The gas switch employed sulfur hexafluoride (SF6) as its insulating medium for miniaturization requirements and was triggered by capillary discharge excited by a pulse transformer for high potential isolation considerations. The influence of a capillary cavity structure and pulse transformer parameters on the switch trigger characteristics was investigated. The results showed that the plasma ejection was enhanced by increasing trigger energy, but was also saturated with a limited cross section of the magnetic core of the pulse transformer, which determined the maximum transferred trigger energy. Employing a long capillary, shrinking nozzle, and small transformer ratio promoted plasma ejection, resulting in an increase in the triggering reliability and lowering the trigger threshold voltage. A 4-mm capillary cavity with a shrinking nozzle driven by a 37/2 pulse transformer was used to trigger an 80-kV SF6 gas switch at a 4.7% operating coefficient, and 1200 times successive and successful triggering was performed, with the trigger delay ranging from 62.5 to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$73~\mu \text{s}$ </tex-math></inline-formula> , which met the technical requirements of rapid control and protection for a 10-kV smart distribution network.

Acute food deprivation-induced relapse to heroin seeking after short and long punishment-imposed abstinence in male rats.

Stress is a major trigger for drug relapse in humans and animal models, even after prolonged abstinence. However, animal models for stress-induced relapse were criticized for the lack of predictive and face validity. Here we investigated the effect of acute food deprivation stress in a novel stress-induced relapse model using voluntary, punishment-imposed abstinence from heroin. We also performed a detailed characterization of the development of punishment-imposed abstinence. Male rats were trained to self-administered heroin (0.1mg/kg/infusion) for 2weeks, using the seeking-taking chained schedule. Pressing the 'seeking' lever led to the insertion of the 'taking' lever and pressing the take lever resulted in heroin infusion. Following self-administration training, rats were exposed to 8 or 21days of heroin-seeking punishment. During punishment, 30% of the completed seek links resulted in a mild escalating footshock instead of take lever presentation. Next, rats were tested for heroin seeking under extinction conditions after 24h of food deprivation and sated conditions. Probabilistic punishment of seeking lever responses resulted in gradual suppression of heroin seeking and taking. Exposure to food-deprivation stress induced a robust relapse to heroin seeking after short and long punishment-imposed abstinence periods, without significant effects of time, i.e., no incubation of heroin seeking. Individual differences were observed in the development of punishment-induced abstinence and stress-induced relapse. These results suggest that stress is a reliable trigger to relapse even after a prolonged period of punishment-induced, voluntary abstinence.

The level-1 trigger for the SuperCDMS experiment at SNOLAB

The SuperCDMS SNOLAB dark matter search experiment aims to be sensitive to energy depositions down to \U0001d4aa(1 eV). This imposes requirements on the resolution, signal efficiency, and noise rejection of the trigger system. To accomplish this, the SuperCDMS level-1 trigger system is implemented in an FPGA on a custom PCB. A time-domain optimal filter algorithm realized as a finite impulse response filter provides a baseline resolution of 0.38 times the standard deviation of the noise, σn, and a 99.9% trigger efficiency for signal amplitudes of 1.1 σn in typical noise conditions. Embedded in a modular architecture, flexible trigger logic enables reliable triggering and vetoing in a dead-time-free manner for a variety of purposes and run conditions. The trigger architecture and performance are detailed in this article.

Low-dose interleukin-2 reverses chronic migraine-related sensitizations through peripheral interleukin-10 and transforming growth factor beta-1 signaling

Low-dose interleukin-2 (LD-IL-2) treatment has been shown to effectively reverse chronic migraine-related behaviors and the sensitization of trigeminal ganglion (TG) neurons through expansion and activation of peripheral regulatory T cells (Tregs) in mice. In this study, we investigated the molecular mechanisms underlying the effects of LD-IL-2 and Treg cells. LD-IL-2 treatment increases the production of cytokines interleukin-10 (IL-10) and transforming growth factor beta-1 (TGFβ1) in T cells, especially Treg cells, suggesting that they may mediate the therapeutic effect of LD-IL-2. Indeed, neutralizing antibodies against either IL-10 or TGFβ completely blocked the effects of LD-IL-2 on the facial mechanical hypersensitivity as well as the sensitization of TG neurons resulting from repeated nitroglycerin (NTG, a reliable trigger of migraine in patients) administration in mice, indicating that LD-IL-2 and Treg cells engage both peripheral IL-10 and TGFβ signaling pathways to reverse chronic-migraine related sensitizations. In an in vitro assay, incubation of TG culture with exogenous IL-10 or TGFβ1 fully reversed NTG-induced sensitization of TG neurons, suggesting that the IL-10 and TGFβ1 signaling in TG neurons contribute to LD-IL-2′s therapeutic effects. Collectively, these results not only elucidate the molecular mechanisms through which LD-IL-2 and Treg cells reverse chronic-migraine related sensitizations, but also suggest that the IL-10 and TGFβ1 signaling pathways in TG neurons are potential targets for chronic migraine therapy.