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Choi, Hojong. "Stacked Transistor Bias Circuit of Class-B Amplifier for Portable Ultrasound Systems." Sensors 19, no. 23 (November 29, 2019): 5252. http://dx.doi.org/10.3390/s19235252.
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The performance of portable ultrasound systems is affected by the excessive heat generated by amplifiers, thereby reducing the sensitivity and resolution of the transducer devices used in ultrasound systems. Therefore, the amplifier needs to generate low amounts of heat to stabilize portable ultrasound systems. To properly control the amplifier, the related bias circuit must provide proper DC bias voltages for long time periods in ultrasound systems. To this end, a stacked transistor bias circuit was proposed to achieve a relatively constant amplifier performance irrespective of temperature variance without any cooling systems as the portable ultrasound system structure is limited. To prove the proposed concept, the performance of the gain and DC current consumption at different experimental times was measured and compared to a developed class-B amplifier with different bias circuits. The amplifier with the stacked transistor bias circuit outperformed with regard to the gain and DC current variance versus time (−0.72 dB and 0.065 A, respectively) compared to the amplifier with a typical resistor divider bias circuit (−5.27 dB and 0.237 A, respectively) after a certain time (5 min). Consequently, the proposed stacked transistor bias circuit is a useful electronic device for portable ultrasound systems with limited structure sizes because of its relatively low gain and DC current variance with respect to time.
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English, Coralie. "Circuit class therapy versus one-to-one therapy sessions." International Journal of Therapy and Rehabilitation 14, no. 5 (May 2007): 202. http://dx.doi.org/10.12968/ijtr.2007.14.5.23536.
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English, Coralie, Julie Bernhardt, Maria Crotty, Adrian Esterman, Leonie Segal, and Susan Hillier. "Circuit Class Therapy or Seven-Day Week Therapy for Increasing Rehabilitation Intensity of Therapy after Stroke (CIRCIT): A Randomized Controlled Trial." International Journal of Stroke 10, no. 4 (March 19, 2015): 594–602. http://dx.doi.org/10.1111/ijs.12470.
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Lynch, Elizabeth, Rachel Harling, Coralie English, and Kathy Stiller. "Patient satisfaction with circuit class therapy and individual physiotherapy." International Journal of Therapy and Rehabilitation 15, no. 4 (April 2008): 167–73. http://dx.doi.org/10.12968/ijtr.2008.15.4.29035.
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Hillier, Susan, Coralie English, Maria Crotty, Leonie Segal, Julie Bernhardt, and Adrian Esterman. "Circuit Class or Seven-Day Therapy for Increasing Intensity of Rehabilitation after Stroke: Protocol of the CIRCIT Trial." International Journal of Stroke 6, no. 6 (November 24, 2011): 560–65. http://dx.doi.org/10.1111/j.1747-4949.2011.00686.x.
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Zanker, Kate, Coralie English, Nicole Prideaux, and Julie Luker. "Interdisciplinary circuit class therapy: Increasing therapy time on an acute stroke unit." International Journal of Therapy and Rehabilitation 14, no. 11 (November 2007): 483–88. http://dx.doi.org/10.12968/ijtr.2007.14.11.27597.
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English, C., and S. Hillier. "Circuit class therapy for improving mobility after stroke: A systematic review." Journal of Rehabilitation Medicine 43, no. 7 (2011): 565–71. http://dx.doi.org/10.2340/16501977-0824.
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Pegito, Irene, Johan Lambeck, Manuel Torres-Parada, José García Vivas Miranda, and Jamile Vivas Costa. "Circuit Class Training in water versus land in Post-Stroke patients: a protocol for a randomized controlled trial." Revista Pesquisa em Fisioterapia 8, no. 3 (September 17, 2018): 377–86. http://dx.doi.org/10.17267/2238-2704rpf.v8i3.2053.
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INTRODUCTION: A high percentage of post-stroke patients have permanent aftermathsdespite conventional rehabilitation. Circuit class training offers an efficient way to achieve structured practice of task-related activities during stroke rehabilitation. Aquatic therapy is another therapeutic approach that offers a great variety of options to be a highly dynamic environment, which helps to improving functionality and recover quality of life and independence in people with disabilities. OBJECTIVE: To develop a protocol for a randomized controlled trial. METHODS: Forty participants will be randomized in two groups: aquatic circuit class training (ACCT) and land circuit class training (LCCT). In both groups, the intervention will be a 7-week class therapy, 3-times weekly, giving a total of 20 sessions, 60 minutes each. Blinded assessors will conduct assessments, using standardized tools: baseline, post-intervention, and 20 days follow-up for the effectiveness of the therapy in terms of gait, balance and upper limb motor function. RESULTS/CONCLUSION: This trial will examine the immediate and medium term effect of an ACCT program as compared to a LCCT program in people with stroke. It has the potential to identify interventions that may improve rehabilitation of these patients. Both CCT programs are based in International Classification of Function, Disability and Health model with activities aimed at impairment, activity and participation levels.
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van Wissen, Kim, and Denise Blanchard. "Circuit class therapy for improving mobility after stroke: A Cochrane review summary." International Journal of Nursing Studies 97 (September 2019): 130–31. http://dx.doi.org/10.1016/j.ijnurstu.2018.10.001.
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English, Coralie, Julie Bernhardt, and Susan Hillier. "Circuit Class Therapy and 7-Day-Week Therapy Increase Physiotherapy Time, But Not Patient Activity." Stroke 45, no. 10 (October 2014): 3002–7. http://dx.doi.org/10.1161/strokeaha.114.006038.
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Wen, Quan, Shangbang Gao, and Mei Zhen. "Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation." Philosophical Transactions of the Royal Society B: Biological Sciences 373, no. 1758 (September 10, 2018): 20170370. http://dx.doi.org/10.1098/rstb.2017.0370.
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The intrinsic oscillatory activity of central pattern generators underlies motor rhythm. We review and discuss recent findings that address the origin of Caenorhabditis elegans motor rhythm. These studies propose that the A- and mid-body B-class excitatory motor neurons at the ventral cord function as non-bursting intrinsic oscillators to underlie body undulation during reversal and forward movements, respectively. Proprioception entrains their intrinsic activities, allows phase-coupling between members of the same class motor neurons, and thereby facilitates directional propagation of undulations. Distinct pools of premotor interneurons project along the ventral nerve cord to innervate all members of the A- and B-class motor neurons, modulating their oscillations, as well as promoting their bi-directional coupling. The two motor sub-circuits, which consist of oscillators and descending inputs with distinct properties, form the structural base of dynamic rhythmicity and flexible partition of the forward and backward motor states. These results contribute to a continuous effort to establish a mechanistic and dynamic model of the C. elegans sensorimotor system. C. elegans exhibits rich sensorimotor functions despite a small neuron number. These findings implicate a circuit-level functional compression. By integrating the role of rhythm generation and proprioception into motor neurons, and the role of descending regulation of oscillators into premotor interneurons, this numerically simple nervous system can achieve a circuit infrastructure analogous to that of anatomically complex systems. C. elegans has manifested itself as a compact model to search for general principles of sensorimotor behaviours. This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.
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English, Coralie K., Susan L. Hillier, Kathy R. Stiller, and Andrea Warden-Flood. "Circuit Class Therapy Versus Individual Physiotherapy Sessions During Inpatient Stroke Rehabilitation: A Controlled Trial." Archives of Physical Medicine and Rehabilitation 88, no. 8 (August 2007): 955–63. http://dx.doi.org/10.1016/j.apmr.2007.04.010.
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Kazior, Thomas E. "Beyond CMOS: heterogeneous integration of III–V devices, RF MEMS and other dissimilar materials/devices with Si CMOS to create intelligent microsystems." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 372, no. 2012 (March 28, 2014): 20130105. http://dx.doi.org/10.1098/rsta.2013.0105.
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Advances in silicon technology continue to revolutionize micro-/nano-electronics. However, Si cannot do everything, and devices/components based on other materials systems are required. What is the best way to integrate these dissimilar materials and to enhance the capabilities of Si, thereby continuing the micro-/nano-electronics revolution? In this paper, I review different approaches to heterogeneously integrate dissimilar materials with Si complementary metal oxide semiconductor (CMOS) technology. In particular, I summarize results on the successful integration of III–V electronic devices (InP heterojunction bipolar transistors (HBTs) and GaN high-electron-mobility transistors (HEMTs)) with Si CMOS on a common silicon-based wafer using an integration/fabrication process similar to a SiGe BiCMOS process (BiCMOS integrates bipolar junction and CMOS transistors). Our III–V BiCMOS process has been scaled to 200 mm diameter wafers for integration with scaled CMOS and used to fabricate radio-frequency (RF) and mixed signals circuits with on-chip digital control/calibration. I also show that RF microelectromechanical systems (MEMS) can be integrated onto this platform to create tunable or reconfigurable circuits. Thus, heterogeneous integration of III–V devices, MEMS and other dissimilar materials with Si CMOS enables a new class of high-performance integrated circuits that enhance the capabilities of existing systems, enable new circuit architectures and facilitate the continued proliferation of low-cost micro-/nano-electronics for a wide range of applications.
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Simonson, Shawn R. "Teaching the Resistance Training Class: A Circuit Training Course Designed for the Strength and Conditioning Coach/Personal Trainer." Strength and Conditioning Journal 32, no. 3 (June 2010): 90–96. http://dx.doi.org/10.1519/ssc.0b013e3181df4502.
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Lawal, I. U., and I. Lawal. "Effectiveness of augmenting therapy time in circuit class therapy on mobility of upper/lower extremity post stroke: a randomized pilot study." Physiotherapy 101 (May 2015): e840-e841. http://dx.doi.org/10.1016/j.physio.2015.03.1658.
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Liao, Ding-An. "Photoelectric Detection System and Machine Learning Recognition Method of Its Detection Images." Journal of Nanoelectronics and Optoelectronics 16, no. 1 (January 1, 2021): 80–88. http://dx.doi.org/10.1166/jno.2021.2907.
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In the photoelectric detection system, the photoelectric detector can convert the optical signal to be measured into a current signal, and the current amplifier transforms the current signal output by the detector into a voltage signal for amplification. In this study, the photo-multiplier tube (PMT) is selected as the photoelectric detector. Compared with other photoelectric detectors, it can obtain higher internal gain, higher sensitivity, and better response performance. The current amplifier is prepared by pre-amplifier and voltage amplifier. In order to capture photoelectric signals well, a large-format scanning system is set up to design each component module, control module, and host computer module of the system. Besides, a machine learning-based algorithm is proposed, namely semi-supervised manifold image recognition algorithm, which is used for identify photoelectric detection images. In the test process, the printed circuit board (PCB) and sapphire material are firstly used as the substrate of the current amplifier, and their influences in the circuit are compared. The peak value of the output noise of each substrate circuit is around 2.8 mV when the input of the current amplifier is short-circuited. Then, the signal gain and signal bandwidth of the photoelectric detection system remain stable when there is no optical signal input. During the process of changing the system signal gain ratio, the noise output of the system is the lowest when the voltage of PMT is 0.50 V and the current amplifier gain is set to 2.2 × 105 V/A. The proposed recognition algorithm can identify different types of targets well. After the image is projected into a two-dimensional space by the algorithm, the distance between classes increases, and the targets in the class promote aggregation, thereby enhancing the identify-ability between samples.
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Blundell, S. W., R. B. Shepherd, C. M. Dean, R. D. Adams, and B. M. Cahill. "Functional strength training in cerebral palsy: a pilot study of a group circuit training class for children aged 4–8 years." Clinical Rehabilitation 17, no. 1 (February 2003): 48–57. http://dx.doi.org/10.1191/0269215503cr584oa.
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George, Mark S. "New Methods of Brain Stimulation Are Improving Research and Therapy in Obsessive-Compulsive Disorder." CNS Spectrums 5, S4 (June 2000): 12–17. http://dx.doi.org/10.1017/s1092852900024986.
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AbstractOver the past decade, new functional neuroimaging tools have enabled researchers to identify the specific brain regions involved in obsessive-compulsive disorder (OCD). More recently, researchers have perfected several new techniques for stimulating the brain. With some exceptions, these new brain stimulation techniques are regionally specific and less invasive than older methods. As a class, these “somatic interventions” build on prior neuroanatomic information about OCD. This article reviews the past and current status of these brain stimulation methodologies, which promise to revolutionize neuropsychiatric research and therapy over the next 10 to 20 years. As the brain circuits in OCD and the pharmacology within those circuits become better understood, these brain stimulation techniques hold particular promise in helping to understand and perhaps treat OCD.
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Morozov, V., T. Nikolaeva, and I. Churelchuluun. "INVESTIGATION AND OPTIMIZATION OF A CLOSED CIRCUIT CRUSHING OF COPPERMOLYBDENUM ORE." Mining science and technology, no. 3 (December 31, 2018): 35–44. http://dx.doi.org/10.17073/2500-0632-2018-3-35-44.
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To control the processes of ore treatment proposed adapted to the conditions of a closed cycle crushing-screening criterion "output productive class -2 + 10 mm", reflecting the effectiveness of all processes. The dependence of the outputs of the individual classes of ore and the proposed optimization criterion parameters of the grinding process shows their relationship with the energy intensity of the process. It is shown that the increase in the load on the screen causes a decrease in the screening efficiency and an increase in the mass fraction of class +2 mm in the circulating ore. Excessive increase in the width of the discharge gap of the crusher causes an increase in the output of the circulating product and an increase in energy consumption. Reducing the discharge gap of less than 7.5 mm leads to an increase in the output of the class - 2 mm. An improved system and algorithm for optical analysis of ore size was proposed and tested. The sensors for controlling the granulometric composition of ore are located above the conveyors for the transportation of over-and under-mortar products of the screening operation. The optical analysis mode provides for the sequential switching on / off of feeding conveyors and crushers, thereby ensuring the flow of the crushed product into the measurement zone from one crusher. The total duration of the analysis of ore from 6 crushers is 12 minutes, which does not affect the final performance of the device of crushing. The application of the developed algorithm can significantly improve the accuracy of the analysis of the size of crushed ore and reduce the power consumption during the processing of ore.
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Baek, Il-Hun, Taesik Lee, Minyoung Song, and Bong-Oh Goo. "Effect of Circuit Class Training for Eight Weeks on Changes in Ratios of F-Trp/BCAAs and Depression in People with Poststroke Depression." Journal of Physical Therapy Science 26, no. 2 (2014): 243–46. http://dx.doi.org/10.1589/jpts.26.243.
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Camillieri, Susan. "A Paradigm Shift for Acute Rehabilitation of Stroke." Journal of Stroke Medicine 2, no. 1 (June 2019): 17–22. http://dx.doi.org/10.1177/2516608519848948.
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Current best practice standards for rehabilitation after stroke call for increasing the dose and intensity of interventions for optimal therapeutic benefit. Despite this, those within inpatient rehabilitation during the acute phase are often sedentary, and they receive a lower dose and intensity of therapy than recommended. This may be due to the lack of therapeutic opportunities outside of therapies, program structure characteristics, or a lack of efficiency in therapeutic encounters, all of which have the potential to reduce therapeutic outcomes. Circuit class therapies and group therapies provide a method of increasing the dose and intensity of therapy provided, and may reduce redundancy and inefficiency within programs, but do not satisfy the 3-hour rule under the current Prospective Payment System in the United States. The Centers for Medicare and Medicaid Services require that individual therapy be the primary mode of intervention provision, which limits programs from providing these evidence-based interventions, at a higher volume in a group or circuit format. Providing an enriched environment outside of structured therapies should be mandated to maximize benefits experienced by patients and reduce sedentary time. Empirical study is required to determine which interventions may be effectively delivered when provided via a nonindividual basis, and to explore the feasibility and fiscal implication of alternative models of care. Reform of regulatory standards may be required to align with best practice standards.
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Bennett, Leanne, Julie Luker, Coralie English, and Susan Hillier. "Stroke survivors’ perspectives on two novel models of inpatient rehabilitation: seven-day a week individual therapy or five-day a week circuit class therapy." Disability and Rehabilitation 38, no. 14 (November 24, 2015): 1397–406. http://dx.doi.org/10.3109/09638288.2015.1103788.
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Van Kessel, Gisela, Susan Hillier, and Coralie English. "Physiotherapists’ attitudes toward circuit class therapy and 7 day per week therapy is influenced by normative beliefs, past experience, and perceived control: A qualitative study." Physiotherapy Theory and Practice 33, no. 11 (August 8, 2017): 850–58. http://dx.doi.org/10.1080/09593985.2017.1357152.
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MIN, LEQUAN, and GUANRONG CHEN. "LOCAL ACTIVITY OF THE VAN DER POL CNN." International Journal of Bifurcation and Chaos 14, no. 07 (July 2004): 2211–22. http://dx.doi.org/10.1142/s0218127404010552.
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This paper studies a class of coupled Van der Pol (CVDP) cellular neural networks (CNNs) that can be realized via a coupled fourth-order circuit with two synaptic currents. The local activity theory, developed by Chua in 1997, is applied to study the CVDP CNN, thereby revealing that the bifurcation diagram of the CVDP CNN has a local activity domain with an edge of chaos, as well as a one-dimensional locally passive domain. Although no chaotic phenomena have been identified in simulations, many complex dynamical behaviors have been observed, such as the co-existence of one-periodic, divergent, and convergent orbits, at the edge of chaos.
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Manzo, Gianluca. "Non-stop dabigatran." AboutOpen 4, no. 1 (October 4, 2018): 158–61. http://dx.doi.org/10.19156/abtpn.2018.0066.
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The transcatheter ablation of atrial fibrillation (AF) is an important therapeutic option for patients with AF who need rhythm monitoring. Since the procedure is associated with the risk of thromboembolic events and bleeding, the choice of this option must take into account all possible alternatives, estimated outcomes, risks and patient preferences.
We report the case of an elderly patient suffering from hypertension and dyslipidemia, without previous ischemic heart disease, with a previous episode of AF cardiovertited with class 1 antiarrhythmics and since then in treatment with flecainide and dabigatran. The patient presented with typical symptomatic atrial flutter, despite the antiarrhythmic therapy, and for which radiofrequency ablation procedure was performed without suspending dabigatran, with drug administration in the morning and evening of the exam.
In line with the safety profile emerging from all trials with dabigatran, the RE-CIRCUIT study results support the preferential use of uninterrupted therapy with dabigatran compared to warfarin in patients with AF subjected to ablation: as demonstrated by this clinical case, the uninterrupted administration of dabigatran combines greater simplicity in the management of anticoagulant therapy with better control of the bleeding risk associated with the procedure, with clear advantages on clinical outcome (Cardiology).
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Fa'atin, Salmah, and Atika Ulfia Adlina. "Circumflex Model of Family Therapy: Initiating Its Application on Parenting Mistakes to Child Early Age." KONSELING RELIGI Jurnal Bimbingan Konseling Islam 10, no. 1 (June 26, 2019): 174. http://dx.doi.org/10.21043/kr.v10i1.5533.
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<p class="06IsiAbstrak">The golden age in the development of early childhood requires more attention amid the emergence of the phenomenon of shifting family functions in the millennial era. Father's function and mothers who experience shifts are thought to have the potential for emergence of parenting problems. The golden age is in need of good parenting, because an error of parenting during this period a significant impact on adulthood. This requires family therapy that is good and feasible to be used in intervening in cases of parenting errors with early childhood. This article aims to describe the theory of family therapy in the circumflex model popularized by Olson, analyzing and initiating its application in cases of parenting errors in early childhood. The idea of applying the therapy is complemented by the design of the stages and forms of therapy. The results of the study show that theoretically it is possible to apply circumcision family model therapy in cases of early childhood parenting errors, because early childhood leads to an internal problem three important dimensions in the circuit model to create a healthy and balanced family, namely the dimensions of closeness, adaptability or flexibility and family communication. The therapeutic design for families who experience parenting errors in early childhood is arranged in stages, stages or sessions of one to ten.</p>
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English, Coralie, Susan Hillier, and Kathy Stiller. "Incidence and severity of shoulder pain does not increase with the use of circuit class therapy during inpatient stroke rehabilitation: a controlled trial." Australian Journal of Physiotherapy 54, no. 1 (2008): 41–46. http://dx.doi.org/10.1016/s0004-9514(08)70065-5.
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Hassett, Leanne M., Anne M. Moseley, Bhavini Whiteside, Siobhan Barry, and Taryn Jones. "Circuit class therapy can provide a fitness training stimulus for adults with severe traumatic brain injury: a randomised trial within an observational study." Journal of Physiotherapy 58, no. 2 (June 2012): 105–12. http://dx.doi.org/10.1016/s1836-9553(12)70090-5.
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Martins, Júlio, João Cardoso, Samuel Honório, and Adriana Silva. "The Effect of a Strength Training Programme in Adolescents in Physical Education Classes (El efecto de un programa de entrenamiento de fuerza en adolescentes en clases de educación física)." Retos, no. 38 (November 26, 2019): 71–76. http://dx.doi.org/10.47197/retos.v38i38.72221.
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Abstract. Introduction: The motivation in Physical Education classes declines as students continue their studies, so its important programs that motivate and arouse interest in learning these themes, adding several and different approaches in these classes. Objective: The objective of the present study was to verify if the application of a strength circuit in high-school students could cause improvements in the strength of the upper and lower limbs. Methods: We evaluated 44 students (M = 24 / F = 20) of the 12th year in high school (EG = 22 students and CG = 22 students). Results: Significant differences in the post-test were observed in the horizontal jump, with a higher mean in the experimental group compared to the control group. In the 1kg medical ball throwing the differences were significant in both moments (pre and post-test), when comparing the groups, with a superior mean in the experimental group. In the 3 kg medicinal ball throwing, significant differences were also observed in both moments, comparing the performance of both groups. The push-up tests did not present significant differences in the pre-test, but showed significant differences in the post-test, with higher means in the experimental group. Conclusions: Through the applied training program, with a duration of 15 minutes, it was possible to verify that the experimental group obtained higher gains, when compared to the control group, for all the variables under study.Resumen. Introducción: la motivación en las clases de Educación Física disminuye a medida que los estudiantes continúan sus estudios, por lo que sus importantes programas motivan y despiertan interés en aprender estos temas, agregando vários Y diferentes enfoques en estas clases. Objetivo: El objetivo del presente estudio fue verificar si la aplicación de un circuito de fuerza en estudiantes de escuela secundaria podría causar mejoras en la fuerza de las extremidades superiores e inferiores. Métodos: Evaluamos 44 estudiantes (M = 24 / F = 20) del 12 ° año en la escuela secundaria (EG = 22 estudiantes y CG = 22 estudiantes). Resultados: Se observaron diferencias significativas en la prueba posterior en el salto horizontal, con p <0.05, con una media más alta en el grupo experimental en comparación con el grupo control. En el lanzamiento de balón médico de 1 kg, las diferencias fueron significativas en ambos momentos (antes y después de la prueba), al comparar los grupos, con una media superior en el grupo experimental. En el lanzamiento de balón medicinal de 3 kg, también se observaron diferencias significativas en ambos momentos, comparando el rendimiento de ambos grupos. Las pruebas de flexión no presentaron diferencias significativas en la prueba previa, pero mostraron diferencias significativas en la prueba posterior, con medias más altas en el grupo experimental. Conclusiones: A través del programa de entrenamiento aplicado, con una duración de 15 minutos, fue posible verificar que el grupo experimental obtuvo mayores ganancias, en comparación con el grupo de control, para todas las variables en estudio.
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Kondratyeva, E. I., N. D. Odinaeva, V. D. Sherman, A. S. Efremova, Yu L. Melyanovskaya, N. V. Bulatenko, T. B. Bukharova, and D. V. Goldshtein. "A clinical case of cystic fibrosis patient with pathogenic N1303K genotype variant with assessment of the CFTR channel function by intestinal current measurement and forskolin-induced swelling in rectal organoids." Almanac of Clinical Medicine 49, no. 3 (July 17, 2021): 219–25. http://dx.doi.org/10.18786/2072-0505-2021-49-019.
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Rationale: Cystic fibrosis is a common monogenic disease related to pathogenic nucleotide sequence variants in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) (ABCC7) gene. The CFTR gene consists of 27 exons and is located in the 31.1 region on the long arm of chromosome 7 (7q31.1). The use of the sequencing method has led to the accumulation of new information about the diversity of genetic variants in cystic fibrosis. This information is important considering approaches to the development of targeted therapy for the disease, based on an individual genotype. No targeted therapy has been developed for the N1303K class II genetic variant. The function of the chloride channel in this mutation has not been compared with that in class II mutations like F508del.Materials and methods: We have analyzed medical files of a patient with cystic fibrosis and F508del/N1303K CFTR genotypes, including the results of rectal biopsy samples. The assessments included measurement of the intestinal potential difference and forskolin-induced swelling assay (FIS) in rectal organoids, with the results being analyzed in relation to the clinical data.Results: The results of intestinal current measurements (ICM) confirm that the N1303K genetic variant is “severe” and leads to the loss of the working CFTR protein, which is consistent with the clinical manifestations. The mean short circuit currency density (ΔISC) in response to amiloride (sodium channel stimulation) was -39 ± 1.22 µA/cm2, to forskolin (chloride channel stimulation) 3.83 ± 1.43 µA/cm2, to carbachol 6 ± 2.47 µA/cm2, and to histamine 8.5 ± 3.02 µA/cm2.FIS results indicate that the VX-770 potentiator and the VX-809 corrector have a weak effect on the stimulation of organoids by forskolin in the genetic variant N1303K: organoid swelling was non-significant (about 20% from their baseline size).Conclusion: The use of the ICM method and FIS assay in human intestinal organoids makes it possible to quantify the work of the CFTR protein and determine the in vitro effectiveness of targeted therapy in patients with cystic fibrosis. CFTR modulators are ineffective in patients with N1303K mutation in the compound-heterozygous condition with F508del, despite both pathogenic variants belong to class II.
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Samidurai, Arun, Rakesh C. Kukreja, and Anindita Das. "Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases." Oxidative Medicine and Cellular Longevity 2018 (August 23, 2018): 1–23. http://dx.doi.org/10.1155/2018/6141902.
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Mechanistic/mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase of the phosphoinositide 3-kinase- (PI3K-) related kinase family, elicits a vital role in diverse cellular processes, including cellular growth, proliferation, survival, protein synthesis, autophagy, and metabolism. In the cardiovascular system, the mTOR signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of both physiological and pathological processes. MicroRNAs (miRs), a class of short noncoding RNA, are an emerging intricate posttranscriptional modulator of critical gene expression for the development and maintenance of homeostasis across a wide array of tissues, including the cardiovascular system. Over the last decade, numerous studies have revealed an interplay between miRNAs and the mTOR signaling circuit in the different cardiovascular pathophysiology, like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation, and atherosclerosis. In this review, we provide a comprehensive state of the current knowledge regarding the mechanisms of interactions between the mTOR signaling pathway and miRs. We have also highlighted the latest advances on mTOR-targeted therapy in clinical trials and the new perspective therapeutic strategies with mTOR-targeting miRs in cardiovascular diseases.
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Boulton, Christopher. "Under the Cloak of Whiteness: A Circuit of Culture Analysis of Opportunity Hoarding and Colour-blind Racism Inside US Advertising Internship Programs." tripleC: Communication, Capitalism & Critique. Open Access Journal for a Global Sustainable Information Society 13, no. 2 (September 30, 2015): 390–403. http://dx.doi.org/10.31269/triplec.v13i2.592.
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Drawing on qualitative fieldwork at three large agencies, this article adapts Richard Johnson’s “circuit of culture” (1986) as a framework to examine both the material practices that help reproduce an overwhelmingly white labour force within US advertising agencies and the ideological screens that conceal them from scrutiny, critique, and reform. I argue that efforts to diversify advertising through internship-based affirmative action programs are ultimately undermined and overwhelmed by the more widespread systems of white privilege whereby agency executives and powerful clients bypass the application process and directly place personal friends and relatives into highly sought after internship slots. Furthermore, I contend that such material practices of class preference are masked, and thereby enabled, by ideological screens of colour-blind meritocracy. I argue that colour-blindness leads to meritocracy in theory, but race discrimination in practice, and conclude with a discussion of some possible implications for communication theory in general and critical media industry studies in particular.
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BROWN, RAY, and LEON O. CHUA. "DYNAMICAL SYNTHESIS OF POINCARÉ MAPS." International Journal of Bifurcation and Chaos 03, no. 05 (October 1993): 1235–67. http://dx.doi.org/10.1142/s0218127493001008.
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We present a theory of constructive Poincaré maps. The basis of our theory is the concept of irreducible nonlinear maps closely associated to concepts from Lie groups. Irreducible nonlinear maps are, heuristically, nonlinear maps which cannot be made simpler without removing the nonlinearity. A single irreducible map cannot produce chaos or any complex nonlinear effect. It can be implemented in an electronic circuit, and there are only a finite number of families of irreducible maps in any n-dimensional space. The composition of two or more irreducible maps can produce chaos and most of the maps studied today that produce chaos are compositions of two or more irreducible maps. The composition of a finite number of irreducible maps is called a completely reducible map and a map which can be approximated pointwise by completely reducible maps is called a reducible map. Poincaré maps from sinusoidally forced oscillators are the most familiar examples of reducible maps. This theoretical framework provides an approach to the construction of "closed form" Poincaré maps having the properties of Poincaré maps of systems for which the Poincaré map cannot be obtained in closed form. In particular, we derive a three-dimensional ODE for which the Hénon map is the Poincaré map and show that there is no two-dimensional ODE which can be written down in closed form for which the Hénon map is the Poincaré map. We also show that the Chirikov (standard) map is a Poincaré map for a two-dimensional closed form ODE. As a result of our theory, these differential equations can be mapped into electronic circuits, thereby associating them with real world physical systems. In order to clarify our results with respect to the abstract mathematical concept of suspension, which says that every C1 invertible map is a Poincaré map, we introduce the concept of a constructable Poincaré map. Not every map is a constructable Poincaré map and this is an important distinction between dynamical synthesis and abstract nonlinear dynamics. We also show how to use any one-dimensional map to induce a two-dimensional Poincaré map which is a completely reducible map and hence for a very broad class of maps that includes the logistic map we derive closed form ODEs for which these one-dimensional maps are "embedded" in a Poincaré map. This provides an avenue for the study of one-dimensional maps, such as the logistic map, as two-dimensional Poincaré maps that arise from square-wave forced electronic circuits.
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Chen, Zhoumou, Timothy M. Doyle, Livio Luongo, Tally M. Largent-Milnes, Luigino Antonio Giancotti, Grant Kolar, Silvia Squillace, et al. "Sphingosine-1-phosphate receptor 1 activation in astrocytes contributes to neuropathic pain." Proceedings of the National Academy of Sciences 116, no. 21 (May 8, 2019): 10557–62. http://dx.doi.org/10.1073/pnas.1820466116.
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Neuropathic pain afflicts millions of individuals and represents a major health problem for which there is limited effective and safe therapy. Emerging literature links altered sphingolipid metabolism to nociceptive processing. However, the neuropharmacology of sphingolipid signaling in the central nervous system in the context of chronic pain remains largely unexplored and controversial. We now provide evidence that sphingosine-1-phosphate (S1P) generated in the dorsal horn of the spinal cord in response to nerve injury drives neuropathic pain by selectively activating the S1P receptor subtype 1 (S1PR1) in astrocytes. Accordingly, genetic and pharmacological inhibition of S1PR1 with multiple antagonists in distinct chemical classes, but not agonists, attenuated and even reversed neuropathic pain in rodents of both sexes and in two models of traumatic nerve injury. These S1PR1 antagonists retained their ability to inhibit neuropathic pain during sustained drug administration, and their effects were independent of endogenous opioid circuits. Moreover, mice with astrocyte-specific knockout of S1pr1 did not develop neuropathic pain following nerve injury, thereby identifying astrocytes as the primary cellular substrate of S1PR1 activity. On a molecular level, the beneficial reductions in neuropathic pain resulting from S1PR1 inhibition were driven by interleukin 10 (IL-10), a potent neuroprotective and anti-inflammatory cytokine. Collectively, our results provide fundamental neurobiological insights that identify the cellular and molecular mechanisms engaged by the S1PR1 axis in neuropathic pain and establish S1PR1 as a target for therapeutic intervention with S1PR1 antagonists as a class of nonnarcotic analgesics.
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Semenov, A. Yu, and A. M. Malakhov. "Circaid adjustable inelastic compression wraps for the treatment of lower limb edema in the venous system pathology." Нospital-replacing technologies:Ambulatory surgery, no. 3-4 (November 16, 2019): 12–16. http://dx.doi.org/10.21518/1995-1477-2019-3-4-12-16.
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Symptoms of chronic venous insufficiency have been known since antiquity. The prevalence of chronic venous insufficiency in Western Europe and the USA has been reported within the range from from 1 to 40% in women and from 1 to 17% in men [1]. As reported by the European authors, the average prevalence of chronic venous insufficiency with class C2-C6 (according to the CEAP classification) among the European population reaches 30% [2]. Edema syndrome remains one of the leading manifestations of chronic venous disease. Compression therapy is one of the main ways to combat edema. The arsenal of devices for the treatment of edematous syndrome is steadily expanding with the development of medical science. Today, in addition to inelastic compression wrap and elastic compression garments, brand-new compression products, circaid adjustable inelastic compression wraps are available.
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Lüscher, Bernhard, and Hanns Möhler. "Brexanolone, a neurosteroid antidepressant, vindicates the GABAergic deficit hypothesis of depression and may foster resilience." F1000Research 8 (May 29, 2019): 751. http://dx.doi.org/10.12688/f1000research.18758.1.
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The GABAergic deficit hypothesis of depression states that a deficit of GABAergic transmission in defined neural circuits is causal for depression. Conversely, an enhancement of GABA transmission, including that triggered by selective serotonin reuptake inhibitors or ketamine, has antidepressant effects. Brexanolone, an intravenous formulation of the endogenous neurosteroid allopregnanolone, showed clinically significant antidepressant activity in postpartum depression. By allosterically enhancing GABAA receptor function, the antidepressant activity of allopregnanolone is attributed to an increase in GABAergic inhibition. In addition, allopregnanolone may stabilize normal mood by decreasing the activity of stress-responsive dentate granule cells and thereby sustain resilience behavior. Therefore, allopregnanolone may augment and extend its antidepressant activity by fostering resilience. The recent structural resolution of the neurosteroid binding domain of GABAA receptors will expedite the development of more selective ligands as a potential new class of central nervous system drugs.
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Espay, Alberto J., Scott Ries, Thomas Maloney, Jennifer Vannest, Erin Neefus, Alok K. Dwivedi, Jane B. Allendorfer, et al. "Clinical and neural responses to cognitive behavioral therapy for functional tremor." Neurology 93, no. 19 (October 4, 2019): e1787-e1798. http://dx.doi.org/10.1212/wnl.0000000000008442.
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ObjectivesTo evaluate changes in tremor severity and motor/emotion-processing circuits in response to cognitive behavioral therapy (CBT) delivered as treatment for functional tremor (FT), the most common functional movement disorder in adults.MethodsFifteen patients with FT underwent fMRI with motor, basic-emotion, and intense-emotion tasks before and after 12 weeks of CBT. Baseline fMRI was compared to those of 25 healthy controls (HCs). The main clinical endpoint was the tremor score (sum of severity, duration, and incapacitation subscores) adapted from the Rating Scale for Psychogenic Movement Disorders (PMDRS) assessed by a blinded clinician. CBT responders were defined as those with PMDRS score reduction >75%. Anatomic and functional brain images were obtained with a 4T MRI system. Generalized linear model and region-of-interest analyses were used to evaluate before-versus-after treatment-related changes in brain activation.ResultsCBT markedly reduced tremor severity (p < 0.01) with remission/near remission achieved in 73.3% of the cohort. Compared to HCs, in those with FT, a functionally defined fMRI region of interest in the anterior cingulate/paracingulate cortex showed increased activation at baseline and decreased activation after CBT during basic-emotion processing (p = 0.012 for CBT responders). Among CBT responders, the change in anterior cingulate/paracingulate was more significant in those with more severe baseline depression (r = 0.75, p < 0.01).ConclusionsTremor severity improved significantly after CBT. The improvement was associated with changes in the anterior cingulate/paracingulate activity, which may represent a marker of emotional dysregulation in FT and a predictor of treatment response.Classification of evidenceThis study provides Class III evidence that CBT significantly improves tremor severity in patients with functional tremor.
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Karafa, Marian, Anna Karafová, and Andrzej Szuba. "A compression device versus compression stockings in long-term therapy of lower limb primary lymphoedema after liposuction." Journal of Wound Care 29, no. 1 (January 2, 2020): 28–35. http://dx.doi.org/10.12968/jowc.2020.29.1.28.
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Objective: Primary lymphoedema is rare and in most cases develops in the lower extremities. In some cases, conservative treatment is insufficient and can be supported by surgical procedure. The aim of this case study was to show the difference in the effectiveness of a compression wrap device and compression stockings in the treatment of primary lymphoedema. Method: Before and after liposuction the patient was treated on an outpatient basis every day for three weeks. This consisted of complex decongestive therapy (CDT) including manual lymph drainage, tailored exercises, skin and nail care, compression therapy and intermittent pneumatic compression. After CDT, the patient was provided with a flat-knit compression garment. Measurements were taken at one week and at three months of wearing the compression garment. The oedema severity was measured by summary calculation method. For both healthy and swollen limbs, the sum of circumferences taken at nine fixed measuring points was determined. The difference between these sums expressed in percents was presented as a relative metric coefficient of leg lymphoedema (RMCL). Results: At the start of therapy, the difference in circumference between the healthy and swollen limb was 21.85%. After CDT (RMCL: 13.46%), the patient was provided with a flat-knit compression stocking (class 3). After one week, the RMCL was 15.92%, while after three months RCML was 20.84%. Because fluid retention was observed the patient was again treated with CDT (RMCL: 13.89%). The patient was provided with compression stocking (class 4). After one week of wearing, the RMCL was 15.77%, while after three months RMCL was 20.26%. As the results proved unsatisfactory, the patient was treated with CDT (RMCL: 13.60%) and a combination of two class 4 compression stockings was used. After one week, RMCL was 14.91%, while after three months RMCL was 19.25%. As the effects of oedema reduction were insufficient, the patient was treated again with CDT (RMCL: 13.89%) and advised to replace one of the stockings with a CirAid device (adjustable compression wrap). After one week, RMCL was 14.18% and after three months RMCL was 14.76%. The patient then qualified for liposuction (RMCL: 7.81%). At three months after surgery, the compression stocking was replaced by an adjustable compression wrap, to reduce the difference in circumference between healthy and swollen limbs (from 21.85 % to 8.68%). Conclusion: This case study shows that in primary oedema one class of compression garment is not always sufficient, nor is the combination of two garments with varying degrees of compression. In some cases, the situation requires the use of non-elastic leg binders such as a CircAid device which, thanks to its greater stiffness, helps improve clinical outcomes.
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Renaud-Bezot, Nick, and Mark Beesley. "Making New With Old." International Symposium on Microelectronics 2012, no. 1 (January 1, 2012): 000687–93. http://dx.doi.org/10.4071/isom-2012-wa53.
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In the past few years, embedding has emerged as a valid contender to traditional packaging technologies for specific applications. It uses PCB (Printed-Circuit Board) processes for 3D integration of active and passive elements to create SiPs (System in Package). Just like MEMS (Micro Electro-Mechanical System) and IPD (Integrated Passive Device) emerged from standard semiconductor processes, and then were adapted to match the specific requirements, so does embedding build on decades-old techniques to create this new class of packages. Inherent advantages include:- Compatibility with traditional SMT processes, in particular with regards to pitch,- Production batch size,- Historical reliability and process data,- Thermal management,- Possibility to integrate EMI shielding,- CTE matching. This paper will present the challenges and opportunities of this packaging technology in terms of processes, performance and reliability. It will focus on the solution developed by AT&S called ECP® (Embedded- Component Packaging). Whereas competition is integrating PCB processes to their semiconductor-packaging operations, AT&S is the only vendor building on its PCB tradition to enter the packaging industry, thereby presenting an alternative view of the subject.
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Staudt, Michael D., Andrea R. Di Sebastiano, Hu Xu, Mandar Jog, Susanne Schmid, Paula Foster, and Matthew O. Hebb. "Advances in Neurotrophic Factor and Cell-Based Therapies for Parkinson's Disease: A Mini-Review." Gerontology 62, no. 3 (September 1, 2015): 371–80. http://dx.doi.org/10.1159/000438701.
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Parkinson's disease (PD) affects an estimated 7-10 million people worldwide and remains without definitive or disease-modifying treatment. There have been many recent developments in cell-based therapy (CBT) to replace lost circuitry and provide chronic biological sources of therapeutic agents to the PD-affected brain. Early neural transplantation studies underscored the challenges of immune compatibility, graft integration and the need for renewable, autologous graft sources. Neurotrophic factors (NTFs) offer a potential class of cytoprotective pharmacotherapeutics that may complement dopamine (DA) replacement and CBT strategies in PD. Chronic NTF delivery may be an integral goal of CBT, with grafts consisting of autologous drug-producing (e.g., DA, NTF) cells that are capable of integration and function in the host brain. In this mini-review, we outline the past experience and recent advances in NTF technology and CBT as promising and integrated approaches for the treatment of PD.
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Kishtagari, Ashwin, Kwok Peng Ng, Charlotte Jarman, Anand D. Tiwari, James G. Phillips, Caroline Schuerger, Babal K. Jha, and Yogenthiran Saunthararajah. "A First-in-Class Inhibitor of ISWI-Mediated (ATP-Dependent) Transcription Repression Releases Terminal-Differentiation in AML Cells While Sparing Normal Hematopoiesis." Blood 132, Supplement 1 (November 29, 2018): 216. http://dx.doi.org/10.1182/blood-2018-99-119311.
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Abstract Acute myeloid leukemia (AML) cells express the PU.1/RUNX1/CEBPA master transcription factor circuit at levels similar to or exceeding that in normal granulocyte-monocyte progenitors (GMP), but somehow terminal granulo-monocytic fates do not occur. Gene expression analyses of AML cells compared to the normal hematopoietic hierarchy confirmed suppression of hundreds of monocyte and granulocyte terminal-differentiation genes that were PU.1 targets by chromatin-immunoprecipitation analyses, despite intact expression of proliferation and myeloid-commitment genes. To better understand this repression rather than activation by the PU.1/RUNX1/CEBPA circuit, we used liquid chromatography-tandem mass spectrometry (LCMS/MS) to analyze the protein composition of the PU.1/RUNX1/CEBPA master transcription factor hub in AML cells of various genotypes. A striking common finding was enrichment for corepressors, coregulators that repress gene transcription, over coactivators that activate genes (we have previously described how leukemia oncoproteins produce this corepressor/coactivator imbalance [e.g., Gu et al., JCI 2018]). Prominent amongst the enriched corepressors were ATP-dependent chromatin remodelers SMARCA5 and CHD4 that execute the critical and energetically expensive event in epigenetic repression of nucleosome positioning to obstruct gene transcription start sites. To translate these observations towards therapy, we used a high throughput screen to identify a first-in-class compound series (ED2-AD101) that inhibits SMARCA5/CHD4. In silico modeling, supported by structure-activity relationship (SAR) studies, surface plasmon resonance and ATP-ase assays, indicated that ED2-AD101 inhibits ISWI family ATP-ase activity allosterically by binding to the highly conserved HELICc-DExx domain. In cell-based assays, ED2-AD101 at doses of between 1 to 10 µM potently suppressed AML cell growth (THP1, KG-1, MV411, HL60, MOLM13) via terminal-differentiation (without early apoptosis) while simultaneously sparing exponential growth of normal CD34+ hematopoietic stem and progenitor cells (Fig.1 A, C, D). We also demonstrated terminal granulo-monocytic differentiation using CD11b/CD14 markers by flow cytometry in THP-1 cells treated with ED2-AD101 at 1 µM dose (Fig 1B). Importantly, these differentiation-based cell cycle exits occurred even in chemo-resistant p53-null AML and other cancer cells (MCF7, UC6, RPMI 8226, and HCT116 cancer cells treated with 10µM of ED2-AD101. In the first panel of Fig. 1E, MCF7 cells show morphologic changes indicative of epithelial differentiation after treatment. Giemsa-stained cytospin preparations of all the above cell lines displayed morphological features of cell differentiation, such as a lower nucleocytoplasmic ratio after treatment) (Fig.1E). The lead compound has pharmaceutical range efficacy in the cell-based assays with GI50 ~ 0.9 µM. The therapeutic index and p53-independent findings are consistent also with our previous pre-clinical and clinical observations using decitabine or 5-azacytidine to inhibit the corepressor DNMT1 in AML cells (reviewed in Velcheti et al., ASCO Ed. Book 2017). Drug pharmacology and pre-clinical in vivo proof-of-principle experiments using patient-derived xenotransplant models of leukemia are in progress. Thus, druggable corepressors are the barriers between AML (and other cancer) cells and the terminal lineage-fates intended by their master transcription factor content, opening the door to novel non-cytotoxic, normal hematopoiesis sparing, differentiation-based oncotherapy. Figure 1. Figure 1. Disclosures Saunthararajah: Novo Nordisk, A/S: Patents & Royalties; EpiDestiny, LLC: Patents & Royalties.
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Hamburger, Agnes E., Breanna DiAndreth, Mark E. Daris, Melanie L. Munguia, Kiran Deshmukh, Jee-Young Mock, Grace E. Asuelime, et al. "Novel CAR T Modules (Tmod) to Target HLA-Class I Loss in Lymphoma." Blood 136, Supplement 1 (November 5, 2020): 23–24. http://dx.doi.org/10.1182/blood-2020-134041.
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Background: Chimeric Antigen Receptor (CAR) T-cell therapy is a proven, powerful clinical modality. However, it is still limited by the fundamental obstacle of cancer therapy: discriminating cancer from normal cells. Current FDA-approved CAR T-cell therapies eliminate normal B cells, leaving patients with B cell aplasia, hypogammaglobulinemia, and susceptible to infection. HLA-Class I loss of heterozygosity (LOH) occurs at an average frequency of ~13% among cancers and specifically ~13% in DLBCL (Broad Institute TCGA database). These losses are irreversible and distinguish the cancer from normal cells. To exploit LOH at the HLA locus, we target the remaining allelic product in tumors with LOH. We evaluated a novel AND NOT Boolean logic gate CAR T module (Tmod) T-cell system to target HLA-A*02 (A2) LOH in lymphoma using both in vitro and in vivo models. Methods: To model tumor cells that have lost A2 via LOH, we used CD19+ Raji lymphoma tumor cells. To model the corresponding "normal" cells, we established CD19+ Raji cells stably expressing A2 (CD19+/A2+ Raji). We then engineered human primary T cells to express a modular signal-integration circuit designed to be activated only by CD19+ lymphoma that do not express A2 (CD19+/A2- Raji). Each primary Tmod CAR T cell expresses both a CD19 activator (A) module using a CD19-targeting 3rd generation CAR, and a separate A2-targeting blocker (B) module using a novel A2-targeting inhibitory receptor. Human primary Tmod CAR T cells were engineered to co-express the A/B modules. First, T cells were stimulated via CD3/CD28 activation, followed by A/B module lentivirus transduction, and enriched for the B module. In vitro Tmod CAR T cells were evaluated for selective killing of CD19+/A2- Raji compared with CD19+/A2+ Raji. For in vivo proof of concept, both CD19+/A2- Raji and CD19+/A2+ Raji cell lines were injected and established into flanks of immunocompromised NGS mice and challenged with adoptive transfer of engineered human primary Tmod CAR T cells. Results: Engineered primary Tmod CAR T cells selectively killed CD19+/A2- Raji and spared CD19+/A2+ Raji (Figure 1). Tmod CAR T cells reversibly cycled from a state of non-killing, "block", to cytotoxicity and back, depending on the CD19+/A2- Raji vs. CD19+/A2+ Raji cells to which they were exposed. Importantly, primary Tmod CAR T cells selectively eliminated only the CD19+/A2- Raji cells in mixed cultures. In vivo, Tmod CAR T cells selectively eradicated CD19+/A2- Raji. More importantly, Tmod CAR T cells did not eradicate CD19+/A2+ Raji in vivo. Conclusions: CD19-targeting Tmod CAR T cells demonstrated robust and selective killing, distinguishing Raji lymphoma lines, one with A2 (CD19+/A2+) and one without (CD19+/A2-), both in vitro and in vivo. A critical requirement for Tmod CAR T-cell therapy is to determine reversibility and lack of anergy in the kill-"block"-kill and "block"-kill-"block" scenarios. This result demonstrates that Tmod CAR T cells do not terminally differentiate into one state (blockade or activation), but rather can switch back and forth as they integrate signals from "normal" and tumor cells. Furthermore, because Tmod CAR T cells can selectively target malignant B cells, it may increase the clinical therapeutic window for CAR T. Tmod CAR T cells may provide a powerful system to address hematologic malignancies and solid tumors with HLA-Class I LOH. Disclosures Hamburger: A2 Biotherapeutics: Current Employment, Current equity holder in private company. DiAndreth:A2 Biotherapeutics: Current Employment. Daris:A2 Biotherapeutics: Current Employment, Current equity holder in private company. Munguia:A2 Biotherapeutics: Current Employment, Current equity holder in private company. Deshmukh:A2 Biotherapeutics: Current Employment. Mock:A2 Biotherapeutics: Current Employment, Current equity holder in private company. Asuelime:A2 Biotherapeutics: Current Employment, Current equity holder in private company. Lim:A2 Biotherapeutics: Current Employment, Current equity holder in private company. Kreke:A2 Biotherapeutics: Current Employment, Current equity holder in private company; Gilead: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Tokatlian:A2 Biotherapeutics: Current Employment, Current equity holder in private company. Maloney:A2 Biotherapeutics: Consultancy, Current equity holder in publicly-traded company, Honoraria; Bioline Rx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria; Gilead Science: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Juno Therapeutics: Consultancy, Honoraria, Patents & Royalties, Research Funding. Go:A2 Biotherapeutics: Current Employment, Current equity holder in private company; Amgen: Current equity holder in publicly-traded company; Allogene: Divested equity in a private or publicly-traded company in the past 24 months; Gilead: Current equity holder in publicly-traded company; Illumina: Divested equity in a private or publicly-traded company in the past 24 months. Kamb:A2 Biotherapeutics: Current Employment, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.
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Rasmussen, Thomas B., and Michael Givskov. "Quorum sensing inhibitors: a bargain of effects." Microbiology 152, no. 4 (April 1, 2006): 895–904. http://dx.doi.org/10.1099/mic.0.28601-0.
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Many opportunistic pathogenic bacteria rely on quorum sensing (QS) circuits as central regulators of virulence expression. In Pseudomonas aeruginosa, QS-regulated gene expression contributes to the formation and maintenance of biofilms and their tolerance to conventional antimicrobials and the host innate immune system. Therefore, QS is an obvious target for a novel class of antimicrobial drugs which would function to efficiently block reception of the cognate QS signals in vivo, and thereby be capable of inducing chemical attenuation of pathogens. As QS is not directly involved in processes essential for growth of the bacteria, inhibition of QS does not impose harsh selective pressure for development of resistance as with antibiotics. Numerous chemical libraries of both natural and synthetic origin have been screened and several QS-inhibitory compounds have been identified. In animal pulmonary infection models, such inhibitors have proven able to significantly improve clearing of the infecting bacteria and reduce mortality. In addition, several enzymes that are able to inactivate the bacterial QS signal molecules have been identified. This inactivation leads to blockage of QS-mediated virulence of plant pathogens in several models.
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Thankappan, Binesh. "A transform of univariable time domain polynomial for extraction of temporal arcs." COMPEL - The international journal for computation and mathematics in electrical and electronic engineering 39, no. 6 (October 16, 2020): 1363–74. http://dx.doi.org/10.1108/compel-01-2020-0029.
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Purpose This paper aims to present a special transformation that is applied to univariable polynomials of an arbitrary order, resulting in the generation of the proposed offset eliminated polynomial. This transform-based approach is used in the analysis and synthesis of temporal arc functions, which are time domain polynomial functions possessing two or more values simultaneously. Using the proposed transform, the submerged values of temporal arcs can also be extracted in measurements. Design/methodology/approach The methodology involves a two-step mathematical procedure in which the proposed transform of the weighted modified derivative of the polynomial is generated, followed by multiplication with a linear or ramp function. The transform introduces a stretching in the temporal or spatial domain depending on the type of variable under consideration, resulting in modifications for parameters such as time derivative and relative velocity. Findings Detailed analysis of various parameters in this modified time domain is performed and results are presented. Additionally, using the proposed methodology, the submerged value of any temporal arc function can also be extracted in measurements, thereby unraveling the temporal arc. Practical implications A typical implementation study with results is also presented for an operational amplifier-based temporal arc-producing square rooting circuit for the extraction of the submerged value of the function. Originality/value The proposed transform-based approach has major applications in extracting the values of temporal arc functions that are submerged in conventional experimental measurements, thereby providing a novel method in unraveling that class of special functions.
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Kabanets, Valentine, Sajin Koroth, Zhenjian Lu, Dimitrios Myrisiotis, and Igor C. Oliveira. "Algorithms and Lower Bounds for De Morgan Formulas of Low-Communication Leaf Gates." ACM Transactions on Computation Theory 13, no. 4 (December 31, 2021): 1–37. http://dx.doi.org/10.1145/3470861.
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The class FORMULA[s]∘G consists of Boolean functions computable by size- s De Morgan formulas whose leaves are any Boolean functions from a class G. We give lower bounds and (SAT, Learning, and pseudorandom generators ( PRG s )) algorithms for FORMULA[n 1.99 ]∘G, for classes G of functions with low communication complexity . Let R (k) G be the maximum k -party number-on-forehead randomized communication complexity of a function in G. Among other results, we show the following: • The Generalized Inner Product function GIP k n cannot be computed in FORMULA[s]° G on more than 1/2+ε fraction of inputs for s=o(n 2 /k⋅4 k ⋅R (k) (G)⋅log(n/ε)⋅log(1/ε)) 2 ). This significantly extends the lower bounds against bipartite formulas obtained by [62]. As a corollary, we get an average-case lower bound for GIP k n against FORMULA[n 1.99 ]∘PTF k −1 , i.e., sub-quadratic-size De Morgan formulas with degree-k-1) PTF ( polynomial threshold function ) gates at the bottom. Previously, it was open whether a super-linear lower bound holds for AND of PTFs. • There is a PRG of seed length n/2+O(s⋅R (2) (G)⋅log(s/ε)⋅log(1/ε)) that ε-fools FORMULA[s]∘G. For the special case of FORMULA[s]∘LTF, i.e., size- s formulas with LTF ( linear threshold function ) gates at the bottom, we get the better seed length O(n 1/2 ⋅s 1/4 ⋅log(n)⋅log(n/ε)). In particular, this provides the first non-trivial PRG (with seed length o(n)) for intersections of n halfspaces in the regime where ε≤1/n, complementing a recent result of [45]. • There exists a randomized 2 n-t #SAT algorithm for FORMULA[s]∘G, where t=Ω(n\√s⋅log 2 (s)⋅R (2) (G))/1/2. In particular, this implies a nontrivial #SAT algorithm for FORMULA[n 1.99 ]∘LTF. • The Minimum Circuit Size Problem is not in FORMULA[n 1.99 ]∘XOR; thereby making progress on hardness magnification, in connection with results from [14, 46]. On the algorithmic side, we show that the concept class FORMULA[n 1.99 ]∘XOR can be PAC-learned in time 2 O(n/log n) .
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Bui, Van-Tien, Van-Toan Nguyen, Ngoc-Anh Nguyen, Reddicherla Umapathi, Liudmila L. Larina, Jong Heon Kim, Hyun-Suk Kim, and Ho-Suk Choi. "Multilayered PVDF-HFP Porous Separator via Phase Separation and Selective Solvent Etching for High Voltage Lithium-Ion Batteries." Membranes 11, no. 1 (January 7, 2021): 41. http://dx.doi.org/10.3390/membranes11010041.
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The development of highly porous and thin separator is a great challenge for lithium-ion batteries (LIBs). However, the inevitable safety issues always caused by poor mechanical integrity and internal short circuits of the thin separator must be addressed before this type of separator can be applied to lithium-ion batteries. Here, we developed a novel multilayer poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) membrane with a highly porous and lamellar structure, through a combination of evaporation-induced phase separation and selective solvent etching methods. The developed membrane is capable of a greater amount of electrolyte uptake and excellent electrolyte retention resulting from its superior electrolyte wettability and highly porous structure, thereby offering better electrochemical performance compared to that of a commercial polyolefin separator (Celgard). Moreover, benefiting from the layered configuration, the tensile strength of the membrane can reach 13.5 MPa, which is close to the mechanical strength of the Celgard type along the transversal direction. The elaborate design of the multilayered structure allows the fabrication of a new class of thin separators with significant improvements in the mechanical and electrochemical performance. Given safer operation, the developed multilayer membrane may become a preferable separator required for high-power and high-energy storage devices.
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Bui, Van-Tien, Van-Toan Nguyen, Ngoc-Anh Nguyen, Reddicherla Umapathi, Liudmila L. Larina, Jong Heon Kim, Hyun-Suk Kim, and Ho-Suk Choi. "Multilayered PVDF-HFP Porous Separator via Phase Separation and Selective Solvent Etching for High Voltage Lithium-Ion Batteries." Membranes 11, no. 1 (January 7, 2021): 41. http://dx.doi.org/10.3390/membranes11010041.
Full textAbstract:
The development of highly porous and thin separator is a great challenge for lithium-ion batteries (LIBs). However, the inevitable safety issues always caused by poor mechanical integrity and internal short circuits of the thin separator must be addressed before this type of separator can be applied to lithium-ion batteries. Here, we developed a novel multilayer poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) membrane with a highly porous and lamellar structure, through a combination of evaporation-induced phase separation and selective solvent etching methods. The developed membrane is capable of a greater amount of electrolyte uptake and excellent electrolyte retention resulting from its superior electrolyte wettability and highly porous structure, thereby offering better electrochemical performance compared to that of a commercial polyolefin separator (Celgard). Moreover, benefiting from the layered configuration, the tensile strength of the membrane can reach 13.5 MPa, which is close to the mechanical strength of the Celgard type along the transversal direction. The elaborate design of the multilayered structure allows the fabrication of a new class of thin separators with significant improvements in the mechanical and electrochemical performance. Given safer operation, the developed multilayer membrane may become a preferable separator required for high-power and high-energy storage devices.
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Nishigaya, Kosuke, Kodai Kishibe, and Katsuaki Tanabe. "Graphene-Quantum-Dot-Mediated Semiconductor Bonding: A Route to Optoelectronic Double Heterostructures and Wavelength-Converting Interfaces." C — Journal of Carbon Research 6, no. 2 (May 9, 2020): 28. http://dx.doi.org/10.3390/c6020028.
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A semiconductor bonding technique that is mediated by graphene quantum dots is proposed and demonstrated. The mechanical stability, electrical conductivity, and optical activity in the bonded interfaces are experimentally verified. First, the bonding scheme can be used for the formation of double heterostructures with a core material of graphene quantum dots. The Si/graphene quantum dots/Si double heterostructures fabricated in this study can constitute a new basis for next-generation nanophotonic devices with high photon and carrier confinements, earth abundance, environmental friendliness, and excellent optical and electrical controllability via silicon clads. Second, the bonding mediated by the graphene quantum dots can be used as an optical-wavelength-converting semiconductor interface, as experimentally demonstrated in this study. The proposed fabrication method simultaneously realizes bond formation and interfacial function generation and, thereby, can lead to efficient device production. Our bonding scheme might improve the performance of optoelectronic devices, for example, by allowing spectral light incidence suitable for each photovoltaic material in multijunction solar cells and by delivering preferred frequencies to the optical transceiver components in photonic integrated circuits.
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Jiang, Xi, Hao Huang, Zejuan Li, Yuanyuan Li, Xiao Wang, Sandeep Gurbuxani, Ping Chen, et al. "Blockade of Mir-150 Maturation by MLL-Fusion/MYC/Lin-28 Is Required for MLL-Associated Leukemia." Blood 120, no. 21 (November 16, 2012): 3499. http://dx.doi.org/10.1182/blood.v120.21.3499.3499.
Full textAbstract:
Abstract Abstract 3499 MicroRNAs (miRNAs), a class of small, non-coding RNAs, are important for posttranscriptional gene regulation in both health and disease. Expression of miRNAs is under stringent regulation at both transcriptional and post-transcriptional levels. Disturbance at either level could cause dysregulation of miRNAs. However, though altered expression of many miRNAs has been reported in various cancers, including acute myeloid leukemia (AML), their dysregulational mechanisms and pathologic functions remain less well understood. Here we report that mature miR-150 level is significantly downregulated in most AML samples, including those with rearrangements of the mixed lineage leukemia (MLL) gene. Strikingly, we found that despite the over 75% decrease of mature miR-150, its primary and precursor transcript abundance is increased to 2∼4 fold in human MLL-associated AML, relative to normal controls. Interestingly, we show that while MLL fusion proteins can bind to the promotor region of miR-150 and promote its primary transcription, they also negatively regulate the maturation process of miR-150 through the MYC/LIN28 functional axis. MiR-150 has been implicated as either an oncogene or a tumor suppressor in various types of solid tumors. However, its function in the pathogenesis of AML is unknown. Here we showed that ectopic expression of miR-150 dramatically inhibited cell growth and promoted apoptosis of human MLL-associated leukemic cells. Furthermore, using colony-forming/replating assays, we found that co-transduction of miR-150 and MLL-AF9 (a fusion gene resulting from t(9;11)) into mouse bone marrow (BM) progenitor cells, caused a significant reduction in colonies (down to 1∼10%; p<0.001, t-test) compared to transduction of MLL-AF9 alone. More importantly, we performed primary BM transplantation (BMT) assays and found that forced expression of miR-150 significantly delayed leukemogenesis mediated by MLL-AF9 (median overall survival, 110 days versus 56 days; p<0.001, log-rank test). We then performed secondary BMT and showed that miR-150+MLL-AF9 leukemic cells developed AML in secondary recipient mice remarkably slower than MLL-AF9 leukemic cells (median overall survival, 70 days vs. 42 days; p<0.001). These findings suggest that miR-150 plays a critical tumor suppressor role in preventing MLL-associated leukemogenesis. Moreover, through a series of studies, we identified Myb and Flt3 as critical direct targets of miR-150 in cell transformation and leukemogenesis. Previous studies have shown that there is an autoregulatory feedback loop between FLT3/MYB and HOXA9/MEIS1, and the latter two are critical downstream targets of MLL fusion proteins. In addition, FLT3 has been identified as an upstream regulator of MYC, while MYC is also a downstream target of MLL fusion proteins and an upstream regulator of Lin28. These previous findings together with the data we reported above suggest that there is a critical MLL-fusion/MYC/LIN28-miR-150-FLT3/MYB/HOXA9/MEIS1 regulatory circuit in MLL-associated leukemia (see Fig. 1). In this circuit, MLL fusion proteins function as the driver, and their presence leads to the significant up-regulation of all six downstream genes, MYC, LIN28, FLT3, MYB, HOXA9, and MEIS1, as well as the primary transcription of miR-150. The up-regulation of MYC/LIN28 results in the blockade of the miR-150 maturation process. This in turn leads to the release of miR-150 inhibition on FLT3 and MYB expression, which would enhance the expression of HOXA9, MEIS1, MYC, and LIN28, and further enhance/maintain the blockade of miR-150 maturation. As a result, the cells reach and maintain high levels of MYC/LIN28/FLT3/MYB/HOXA9/MEIS1, and thereby transform the cells and lead to leukemogenesis. Our further systematic studies confirmed the existence/fidelity of this regulatory circuit in MLL-associated leukemia. Taken together, we revealed a previously unappreciated regulatory circuit. Our findings may advance our understanding of the complex molecular mechanisms underlying the development and maintenance of MLL-associated leukemia, and may also provide new strategies to treat MLL-associated leukemia, a disease that is presently treatment resistant, and likely also other subtypes of AML (as miR-150 is down-regulated in all subtypes of AML), or even other types of cancer that also utilize at least part of the signaling circuit we have described herein. Disclosures: No relevant conflicts of interest to declare.
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Fang, X., and G. A. Clark. "Differential responses of Aplysia siphon motor neurons and interneurons to tail and mantle stimuli: implications for behavioral response specificity." Journal of Neurophysiology 76, no. 6 (December 1, 1996): 3895–909. http://dx.doi.org/10.1152/jn.1996.76.6.3895.
Full textAbstract:
1. Tail shock and mantle shock elicit different forms of siphon responses in Aplysia (flaring and backward bending vs. constriction and forward bending, respectively). Moreover, training with these two unconditioned stimuli (USs) in US-alone or classical conditioning paradigms differentially modifies the direction of the response to a siphon tap subsequently presented. As a first step toward addressing neural mechanisms underlying this response specificity, we systematically mapped the central siphon withdrawal circuit to determine which motor neurons and interneurons are differentially engaged by, and potentially modified by, tail and mantle USs. We utilized semi-intact preparations consisting of the intact mantle organs (including the gill and siphon), the tail, and the abdominal and circumesophageal ganglia. USs were delivered either cutaneously through silver wires implanted in the tail and mantle or via suction electrodes to the tail and branchial nerves. 2. We found that one class of central siphon motor neurons, the LFSB cells, was preferentially activated by tail USs, whereas other siphon motor neurons, the LBs cells and RDs cells, were preferentially activated by mantle USs. These motor neurons thus appear to be the final common path for the differential siphon movements to these USs. In addition, because activation of these cells can elicit neuromuscular facilitation and thereby enhance siphon movements, this differential activation may contribute to behavioral response specificity by imposing a specific response bias. 3. L29 interneurons, which both mediate and modulate the siphon withdrawal response, responded preferentially and exhibited synaptic facilitation selectively in response to tail shock USs. In contrast, L34 and the interneuron II network did not show differential activation. Facilitation at L29-LFSB connections following training with tail shock may contribute to tail-directed siphon responses to siphon tap and may thus be an additional mechanism contributing to behavioral response specificity. Possibly, facilitation at other L29 connections could also enhance its modulatory capabilities. 4. The generation of specific response topographies thus appears to involve the coordinate regulation of diverse neuronal elements and multiple mechanisms, which may contribute to different aspects of learning.