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Hasler, Jennifer, Aishwarya Natarajan, and Sihwan Kim. "Enabling Energy-Efficient Physical Computing through Analog Abstraction and IP Reuse." Journal of Low Power Electronics and Applications 8, no. 4 (November 24, 2018): 47. http://dx.doi.org/10.3390/jlpea8040047.
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This paper shows the first step in analog (and mixed signal) abstraction utilized in large-scale Field Programmable Analog Arrays (FPAA), encoded in the open-source SciLab/Xcos based toolset. Having any opportunity of a wide-scale utilization of ultra-low power technology both requires programmability/reconfigurability as well as abstractable tools. Abstraction is essential both make systems rapidly, as well as reduce the barrier for a number of users to use ultra-low power physical computing techniques. Analog devices, circuits, and systems are abstractable and retain their energy efficient opportunities compared with custom digital hardware. We will present the analog (and mixed signal) abstraction developed for the open-source toolkit used for the SoC FPAAs. Abstraction of Blocks in the FPAA block library makes the SoC FPAA ecosystem accessible to system-level designers while still enabling circuit designers the freedom to build at a low level. Multiple working test cases of various levels of complexity illustrate the analog abstraction capability. The FPAA block library provides a starting point for discussing the fundamental block concepts of analog computational approaches.
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Wei, Shu Hua, Lan Dai, Xiao Bo Zhang, and Yan Feng Jiang. "Efficient and Accurate Testing of On-Chip ADC Based on ATE." Applied Mechanics and Materials 380-384 (August 2013): 3378–81. http://dx.doi.org/10.4028/www.scientific.net/amm.380-384.3378.
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The embedded digital-analog mixed-signal circuit testing has become one of the difficulties to be solved. In this paper, a SoC embedded ADC has been tested based on the Credence Gemini500 verification system. The testing method is studied and verified through the test experiment and results. This testing method is an important reference for general embedded IP core testing.
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Nagarajan, Karthikeyan, Rupshali Roy, Rasit Onur Topaloglu, Sachhidh Kannan, and Swaroop Ghosh. "SCANN: Side Channel Analysis of Spiking Neural Networks." Cryptography 7, no. 2 (March 27, 2023): 17. http://dx.doi.org/10.3390/cryptography7020017.
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Spiking neural networks (SNNs) are quickly gaining traction as a viable alternative to deep neural networks (DNNs). Compared to DNNs, SNNs are computationally more powerful and energy efficient. The design metrics (synaptic weights, membrane threshold, etc.) chosen for such SNN architectures are often proprietary and constitute confidential intellectual property (IP). Our study indicates that SNN architectures implemented using conventional analog neurons are susceptible to side channel attack (SCA). Unlike the conventional SCAs that are aimed to leak private keys from cryptographic implementations, SCANN (SCA̲ of spiking n̲eural n̲etworks) can reveal the sensitive IP implemented within the SNN through the power side channel. We demonstrate eight unique SCANN attacks by taking a common analog neuron (axon hillock neuron) as the test case. We chose this particular model since it is biologically plausible and is hence a good fit for SNNs. Simulation results indicate that different synaptic weights, neurons/layer, neuron membrane thresholds, and neuron capacitor sizes (which are the building blocks of SNN) yield distinct power and spike timing signatures, making them vulnerable to SCA. We show that an adversary can use templates (using foundry-calibrated simulations or fabricating known design parameters in test chips) and analysis to identify the specifications of the implemented SNN.
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ARYANTA, DWI, ARSYAD RAMADHAN DARLIS, and ARDHIANSYAH PRATAMA. "Implementasi Sistem IP PBX menggunakan Briker." ELKOMIKA: Jurnal Teknik Energi Elektrik, Teknik Telekomunikasi, & Teknik Elektronika 1, no. 2 (July 1, 2013): 117. http://dx.doi.org/10.26760/elkomika.v1i2.117.
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ABSTRAKVoIP (Voice over Internet Protocol) adalah komunikasi suara jarak jauh yang digunakan melalui jaringan IP. Pada penelitian ini dirancang sistem IP PBX dengan menggunakan teknologi berbasis VoIP. IP PBX adalah perangkat switching komunikasi telepon dan data berbasis teknologi Internet Protocol (IP) yang mengendalikan ekstension telepon analog maupun ekstension IP Phone. Software VirtualBox digunakan dengan tujuan agar lebih memudahkan dalam sistem pengoperasian Linux yang dimana program untuk membuat IP PBX adalah menggunakan Briker yang bekerja pada Operating System Linux 2.6. Setelah proses penginstalan Briker pada Virtualbox dilakukan implementasi jaringan IP PBX. Setelah mengimplementasikan jaringan IP PBX sesuai dengan topologi, kemudian melakukan pengujian success call rate dan analisis Quality of Service (QoS). Pengukuran QoS menggunakan parameter jitter, delay, dan packet loss yang dihasilkan dalam sistem IP PBX ini. Nilai jitter sesama user Briker (baik pada smartphone maupun komputer) mempunyai rata-rata berada pada nilai 16,77 ms. Sedangkan nilai packetloss yang didapat pada saat terdapat pada saat user 1 sebagai pemanggil telepon adalah 0%. Sedangkan persentase packet loss pada saat user 1 sebagai penerima telepon adalah 0,01%. Nilai delay pada saat berkomunikasi antar user berada pada 11,75 ms. Secara keseluruhan nilai yang didapatkan melalui penelitian ini, dimana hasil pengujian parameter-parameter QOS sesuai dengan standar yang telah direkomendasikan oleh ITU dan didapatkan nilai QoS dengan hasil “baik”.Kata Kunci: Briker, VoIP, QoS, IP PBX, Smartphone.ABSTRACTVoIP (Voice over Internet Protocol) is a long-distance voice communications over IP networks are used. In this study, IP PBX systems designed using VoIP -based technologies. IP PBX is a telephone switching device and data communication technology-based Internet Protocol (IP) which controls the analog phone extensions and IP Phone extensions. VirtualBox software is used in order to make it easier for the Linux operating system to create a program which is using briker IP PBX that works on Linux 2.6 Operating System. After the installation process is done briker on Virtualbox IP PBX network implementation. After implementing the IP PBX network according to the topology, and then do a test call success rate and analysis of Quality of Service (QoS). Measurement of QoS parameters using jitter, delay, and packet loss resulting in the IP PBX system. Jitter value briker fellow users (either on a smartphone or computer) has been on the average value of 16.77 ms. While the values obtained packetloss when there is 1 user when a phone caller is 0%. While the percentage of packet loss at user 1 as a telephone receiver is 0.01%. Delay value when communicating between users located at 11.75 ms. Overall value obtained through this study , where the results of testing the QOS parameters in accordance with the standards recommended by the ITU and the QoS values obtained with the results "good".Keywords: Briker, VoIP, QoS, IP PBX, Smartphone.
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Muthoharo, Muthoharo, Martono Dwi Atmadja, and Abdul Rasyid. "Analysis Of Voice Quality on Aircraft Telephone Through Internet Telephony Gateway in Voice Over Internet Protocol." Jurnal Jartel Jurnal Jaringan Telekomunikasi 12, no. 2 (June 29, 2022): 80–84. http://dx.doi.org/10.33795/jartel.v12i2.309.
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Along with the development of the era, analog telephones have been replaced by IP Phones whose communication range can be wider and more flexible. Therefore, analog telephones are almost forgotten because of the limited communication range. With the addition of ITG (Internet Telephony Gateway) then analog telephones can communicate in VoIP networks. This research will discuss the analysis of voice quality in the communication process between telephone sets via ITG in a VoIP network based on the shape of the input and output, the amplitude response to frequency changes and the delay. Data retrieval is done by using a transmission test set as a substitute for human voice and knowing the amplitude value generated every time there is a change in frequency and an oscilloscope as a tool to determine the shape of the input and output waves as well as the delay. The results of this study indicate that delay generated by communication between analog telephones is <1 ms. When viewed from the form of the information signal generated from communication between telephone sets, that is, the shape of the input and output information signals are both sines, so it can be said that the information signal has not decreased in quality. The amplitude response resulting from frequency changes in communication between analog telephones is, the greater the value of the communication frequency.
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Harris, Hannah Marie, Waseem Gul, Mahmoud A. ElSohly, and Kenneth J. Sufka. "Effects of Cannabidiol and a Novel Cannabidiol Analog against Tactile Allodynia in a Murine Model of Cisplatin-Induced Neuropathy: Enhanced Effects of Sub-Analgesic Doses of Morphine." Medical Cannabis and Cannabinoids 1, no. 1 (June 12, 2018): 54–59. http://dx.doi.org/10.1159/000489077.
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Objective: This research examined whether a cannabidiol (CBD)-opioid pharmacotherapy could attenuate cisplatin-induced tactile allodynia. Methods: Mice (C57BL/6) were given 6 doses of 2.3 mg/kg cisplatin intraperitoneally (IP) on alternating days to induce tactile allodynia as quantified using an electric von Frey (eVF). Test groups in Experiment 1 received either vehicle, 0.1 or 2.5 mg/kg morphine, 1.0 or 2.0 CBD, or the 2 drugs in combination. Test groups in Experiment 2 received either vehicle, 0.1 or 2.5 mg/kg morphine, 1.0, 2.0, 3.0, or 4.0 mg/kg NB2111 (a long-acting CBD analogue), or the 2 drugs in combination. Drugs were administered IP 45 min before eVF assessment. Results: Cisplatin produced tactile allodynia that was attenuated by 2.5 mg/kg morphine. Both CBD and NB2111 produced dose-dependent attenuation of tactile allodynia. CBD and NB2111, given in combination with sub-analgesic doses of morphine, produced attenuation of tactile allodynia equivalent to 2.5 mg/kg morphine. Conclusions: While both CBD and NB2111, either alone or in combination with sub-analgesic doses of opioids, exhibited analgesic effects, NB2111 could be capable of superior analgesia over time by virtue of enhanced pharmacokinetics.
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Nakamaru, Y., Y. Furuta, D. Takagi, N. Oridate, and S. Fukuda. "Preservation of the nasolacrimal duct during endoscopic medial maxillectomy for sinonasal inverted papilloma." Rhinology journal 48, no. 4 (December 1, 2010): 452–56. http://dx.doi.org/10.4193/rhino10.015.
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BACKGROUND: To assess the efficacy of a new endonasal medial maxillectomy technique (EMM) for the treatment of inverted papilloma (IP). METHODOLOGY: A prospective series of 55 consecutive patients diagnosed with IP between March 2002 and April 2009 were entered into this study. The new surgical technique was applied to tumors arising from the anterior part of the maxillary sinus. After conventional EMM, the entire nasolacrimal duct was separated from the bony component of the nasolacrimal canal and preserved. Schirmer`s test and a visual analog scale (VAS) score were used to assess the lacrimal duct function after surgery. RESULTS: Ten of the 55 patients underwent the new surgical procedure. All patients were categorized with stage T3 or T4 tumors. No patients suffered tumor recurrence. There was no difference in lacrimal duct function between the diseased side and healthy side of the nasolacrimal duct. The mean VAS score was 2.8/100. CONCLUSIONS: This new surgical technique preserves the whole length of the nasolacrimal unit. It also offers several advantages including good visualization, nasolacrimal function after surgery and fewer adverse effects such as facial numbness and epiphora.
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Syahrial, Miftah Rahman. "Analisa Quality of Service IP Telephony dengan Metode Low Latency Queuing." Jurnal Telekomunikasi dan Komputer 5, no. 1 (February 27, 2017): 69. http://dx.doi.org/10.22441/incomtech.v5i1.1134.
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Voice over IP pada era modern sekarang ini sudah sangat krusial. Teknologi ini bisa mengatasi permasalahan yang muncul dalam telepon analog atau telepon tradisional ini adalah ketika pengguna, terutama perusahaan, ingin melakukan komunikasi jarak jauh dari pusat ke kantor cabang dimana cost alias biaya yang muncul ketika berkomunikasi dari pusat dan cabang berlangsung lama. Dalam penerapannya, telekomunikasi yang menggunakan teknologi internet, mengalami beberapa hambatan terutama dalam hal packet loss dan delay. Thesis ini membandingkan metode manajemen kongesti Quality of Service (QoS) low latency queuing (LLQ) dengan metode-metode lainnya seperti First in First out (FIFO) dan Class Based Weighted Fair Queuing (CBWFQ). Metode low latency queuing (LLQ) dirancang untuk memprioritaskan paket suara (voice) dan meminimalisir waktu tempuh (delay) yang akan dipakai oleh paket data. Hal ini bisa dicapai karena metode ini adalah gabungan dari metode CBWFQ dan metode Priority Queuing (PQ) yang dirancang untuk memprioritaskan paket suara tapi tidak dirancang untuk memprioritaskan paket data. Hasil yang didapat cukup memuaskan, waktu tempuh (delay) paket suara yang diperoleh dari LLQ untuk ITU-T G.114 (recommended delay untuk one-way connection VoIP) adalah 0,001 detik untuk delay minimumnya dan 0,142 detik untuk delay maksimumnya, dimana jaringan test bed yang dipakai oleh paket data dibuat untuk mencerminkan congested network, sedangkan metode-metode lain seperti FIFO dan CBWFQ melebihi acceptable delay yang direkomendasikan oleh ITU-T G.114. Sedangkan pengaruh implementasi LLQ terhadap codec yang dijalankan tidak banyak berubah, untuk delay yang dihasilkan codec G.729br8 cukup stabil dan delay dari codec G.711ulaw masih cenderung meningkat terkait dari lamanya sesi percakapan walaupun masih sesuai standar yang diterapkan oleh ITU-T.
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Benito, Javier, Beatriz Monteiro, Anne-Marie Lavoie, Guy Beauchamp, B. Duncan X. Lascelles, and Paulo V. Steagall. "Analgesic efficacy of intraperitoneal administration of bupivacaine in cats." Journal of Feline Medicine and Surgery 18, no. 11 (July 11, 2016): 906–12. http://dx.doi.org/10.1177/1098612x15610162.
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Objectives The aim of this study was to evaluate the analgesic efficacy of intraperitoneal (IP) bupivacaine in cats undergoing ovariohysterectomy (OVH). Methods Forty-five cats were included in a randomized, prospective, blinded study after owners’ written consent was obtained. The anesthetic protocol included acepromazine–buprenorphine–propofol–isoflurane. A ventral midline incision was made and cats (n = 15/group) were administered either IP saline 0.9% (negative and positive control groups; NG and PG, respectively) or IP bupivacaine (2 mg/kg; bupivacaine group; BG). Cats in the PG received meloxicam (0.2 mg/kg SC). An OVH was performed and postoperative pain was evaluated using a dynamic interactive visual analog scale (DIVAS), the UNESP-Botucatu multidimensional composite pain scale (MCPS) and mechanical nociceptive thresholds (MNT) for up to 8 h after the end of surgery. Postoperative sedation was evaluated using DIVAS. Rescue analgesia was provided with buprenorphine and/or meloxicam. Repeated measures linear models and a Cochran–Mantel–Haenszel test were used for statistical analysis ( P <0.05). Results There was a significant effect of treatment on the number of times rescue analgesia was administered ( P = 0.002) (PG, n = 2, 13%; NG, n = 12, 80%; BG, n = 4, 27%) with the number of rescues being higher in the NG group than in the PG ( P = 0.0004) and BG ( P = 0.02) groups. The DIVAS, MCPS and MNT were significantly different when compared with baseline values at different time points; however, data were not significantly different among groups. Conclusions and relevance Treatments PG and BG produced similar analgesia in terms of pain scores, number of times rescue analgesia was administered and MNT. Based on rescue analgesia, IP administration of bupivacaine provides analgesia in cats after OVH.
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Spolidoro Paschoal, Natalia de Oliva, Jamil Natour, Flavia S. Machado, Hilda Alcântara Veiga de Oliveira, and Rita Nely Vilar Furtado. "Effectiveness of Triamcinolone Hexacetonide Intraarticular Injection in Interphalangeal Joints: A 12-week Randomized Controlled Trial in Patients with Hand Osteoarthritis." Journal of Rheumatology 42, no. 10 (August 1, 2015): 1869–77. http://dx.doi.org/10.3899/jrheum.140736.
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Objective.To evaluate the effectiveness and tolerance of intraarticular injection (IAI) of triamcinolone hexacetonide (TH) for the treatment of osteoarthritis (OA) of hand interphalangeal (IP) joints.Methods.Sixty patients who underwent IAI at the most symptomatic IP joint were randomly assigned to receive TH/lidocaine (LD; n = 30) with TH 20 mg/ml and LD 2%, or just LD (n = 30). The injected joint was immobilized with a splint for 48 h in both groups. Patients were assessed at baseline and at 1, 4, 8, and 12 weeks by a blinded observer. The following variables were assessed: pain at rest [visual analog scale (VAS)r], pain at movement (VASm), swelling (physician VASs), goniometry, grip and pinch strength, hand function, treatment improvement, daily requirement of paracetamol, and local adverse effects. The proposed treatment (IAI with TH/LD) was successful if statistical improvement (p < 0.05) was achieved in at least 2 of 3 VAS. Repeated-measures ANOVA test was used to analyze intervention response.Results.Fifty-eight patients (96.67%) were women, and the mean age was 60.7 years (± 8.2). The TH/LD group showed greater improvement than the LD group for VASm (p = 0.014) and physician VASs (p = 0.022) from the first week until the end of the study. In other variables, there was no statistical difference between groups. No significant adverse effects were observed.Conclusion.The IAI with TH/LD has been shown to be more effective than the IAI with LD for pain on movement and joint swelling in patients with OA of the IP joints. Regarding pain at rest, there was no difference between groups. Trial registration number: ClinicalTrials.gov (NCT02102620).
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Ramos, Alexis Rebecca, Matthew Smith, Heena Panchal, and Adam Mailloux. "Abstract 2997: Tumor hypoxia blocks the induction of antigen processing machinery." Cancer Research 83, no. 7_Supplement (April 4, 2023): 2997. http://dx.doi.org/10.1158/1538-7445.am2023-2997.
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Abstract Antigen presentation is critical for adaptive immune response to cancer but is often subverted to evade immune response. While hypoxia is a pervasive feature of solid tumors, it’s role in tumor antigen processing remains understudied. To assess the effects of reduced oxygen on antigen processing machinery, we used interferon (IFN)-γ to induce the expression of the immunoproteasome (IP), a proteasome isoform critical for the tumor antigen processing, in A549 human lung cancer cells cultured under 20% O2, or 2% O2. Treatment with IFN-γ induced protein expression of IP subunits LMP2, LMP7, and MECL-1 in a dose-dependent manner under 20% O2 as assessed by western blotting. In contrast, IFN-γ failed to induce protein expression of these subunits under hypoxic conditions. We observed similar blockades of other antigen processing pathway components in response to IFN-γ under hypoxic conditions including TAP, tapasin, and calreticulin, as well as secondary mediators of IFN-γ-stimulated genes including several members of the interferon regulatory factor (IRF) family. Surprisingly, under identical conditions, induction of IP subunit mRNAs appear intact under hypoxia as assessed by RT-PCR, with similar levels of LMP2, LMP7, and MECL-1 upregulated by IFN-γ regardless of oxygen level, suggesting hypoxic IP blockade occurs post-transcriptionally or post-translationally. In line with this notion, primary mediators of IFN-γ signaling, including phosphorylated (Tyr701) STAT1 levels were unaffected by oxygen levels. To investigate the mechanism behind this phenomenon, we created hypoxia-inducible factor (HIF)-1a and/or HIF-2a knockout A549 cell lines or used cobalt chloride (CoCl2), a hydroxylase inhibitor, to directly interrogate the hypoxia signaling pathway. Blockade of IP subunit induction in response to IFN-γ was not observed after CoCl2 treatment, nor did HIF-1a and/or HIF-2a genetic deletion rescue IP subunit blockade in A549 cells cultured under hypoxia, indicating that hypoxia-induced IP blockade is independent of the HIF pathway. To test if this phenomenon is regulated by epigenic means, we treated cells with 5-Azacytidine (5-aza), a cystine analog nucleoside, and observed a re-establishment of IP subunit protein expression under hypoxia in response to IFN-γ. Given that 5-aza preferentially integrates RNA over DNA, and that IP subunit mRNA levels appear unaffected by hypoxia, suggests that hypoxia-induced IP blockade may be due to hypoxia-specific cytosine modifications within mRNA transcripts. Current studies include efforts to map mRNA methylation patterns and interrogate mRNA methylation transferases under hypoxic conditions. These studies introduce a novel link between hypoxia and reduced cancer cell antigen processing machinery and may help identify druggable epigenetic targets that can be used to enhance the immunogenicity of hypoxic tumors. Citation Format: Alexis Rebecca Ramos, Matthew Smith, Heena Panchal, Adam Mailloux. Tumor hypoxia blocks the induction of antigen processing machinery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2997.
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Saad, N. M., N. S. M. Noor, A. R. Abdullah, O. Y. Fong, and N. N. S. A. Rahman. "Real-Time LCD Digit Recognition System." Indonesian Journal of Electrical Engineering and Computer Science 6, no. 2 (May 1, 2017): 402. http://dx.doi.org/10.11591/ijeecs.v6.i2.pp402-411.
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<p>In recent years, the utilization of digital instruments in industries is quickly expanding. This is because digital instruments are typically more exact than the analog instruments, and easier to be read as they are hooked up to a liquid-crystal display (LCD). However, manual data entry from LCD display is tedious and less accurate. This paper proposes a real-time LCD digit recognition system for the industrial purposes. The system is interfaced with an IP webcam to capture the video frames from the LCD display. The digital data is pre-processed into grayscale and being cropped into a selected region of interest (ROI). Adaptive thresholding and morphological operation are applied for the digit segmentation process. Data extraction and characterization are done by utilizing neural network classifier. Finally, all the information are logged out to Microsoft Excel spreadsheet. The 90% accuracy is accomplished for 50 test images of various LCD display.</p>
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Burgart, Yanina V., Galina F. Makhaeva, Olga P. Krasnykh, Sophia S. Borisevich, Natalia A. Agafonova, Nadezhda V. Kovaleva, Natalia P. Boltneva, et al. "Synthesis of 4-Aminopyrazol-5-ols as Edaravone Analogs and Their Antioxidant Activity." Molecules 27, no. 22 (November 9, 2022): 7722. http://dx.doi.org/10.3390/molecules27227722.
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One of the powerful antioxidants used clinically is Edaravone (EDA). We synthesized a series of new EDA analogs, 4-aminopyrazol-5-ol hydrochlorides, including polyfluoroalkyl derivatives, via the reduction of 4-hydroxyiminopyrazol-5-ones. The primary antioxidant activity of the compounds in comparison with EDA was investigated in vitro using ABTS, FRAP, and ORAC tests. In all tests, 4-Amino-3-pyrazol-5-ols were effective. The lead compound, 4-amino-3-methyl-1-phenylpyrazol-5-ol hydrochloride (APH), showed the following activities: ABTS, 0.93 TEAC; FRAP, 0.98 TE; and ORAC, 4.39 TE. APH and its NH-analog were not cytotoxic against cultured normal human fibroblasts even at 100 μM, in contrast to EDA. According to QM calculations, 4-aminopyrazolols were characterized by lower gaps, IP, and η compared to 4-hydroxyiminopyrazol-5-ones, consistent with their higher antioxidant activities in ABTS and FRAP tests, realized by the SET mechanism. The radical-scavenging action evaluated in the ORAC test occurred by the HAT mechanism through OH bond breaking in all compounds, directly dependent on the dissociation energy of the OH bond. All the studied compounds demonstrated the absence of anticholinesterase activity and moderate inhibition of CES by some 4-aminopyrazolols. Thus, the lead compound APH was found to be a good antioxidant with the potential to be developed as a novel therapeutic drug candidate in the treatment of diseases associated with oxidative stress.
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Halihal, Ali. "Design and Implementation of Wireless 4-20 mA Current Simulator." Iraqi Journal for Electrical and Electronic Engineering 14, no. 2 (December 1, 2018): 155–63. http://dx.doi.org/10.37917/ijeee.14.2.7.
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This paper presents new device to simulate and inject a 4-20 mA current signal to PLC and control on this signal wirelessly. The proposed simulator device has been designed and implemented by a PIC 18f4520 microcontroller and an Ethernet click. This device is connected to Wireless Local Area Network (WLAN) via Wi-Fi router using TCP/IP protocol. The simulator has two channels for 4-20 mA current output signals with two channels for digital output signals, controlled by a laptop or a smart mobile. The purpose of this work is to demonstrate the usefulness of the Wi-Fi wireless technology for remote controlling on the 4-20 mA output current signal and the digital output signal in the designed simulator device. The experiments indicate that the proposed wireless simulator outputs the 4-20 mA current with high accuracy and very fast response. The experiments also indicate that the proposed wireless simulator is easy, comfortable and convenient practically to use in the test operations of protections, interlocks and integrity of analog input channels for PLC compared to the wired simulator.
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Benter, Ibrahim F., Mariam H. M. Yousif, Constantin Cojocel, May Al-Maghrebi, and Debra I. Diz. "Angiotensin-(1–7) prevents diabetes-induced cardiovascular dysfunction." American Journal of Physiology-Heart and Circulatory Physiology 292, no. 1 (January 2007): H666—H672. http://dx.doi.org/10.1152/ajpheart.00372.2006.
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The aim of this study was to test the hypothesis that treatment with angiotensin-(1–7) [ANG-(1–7)] or ANG-(1–7) nonpeptide analog AVE-0991 can produce protection against diabetes-induced cardiovascular dysfunction. We examined the influence of chronic treatment (4 wk) with ANG-(1–7) (576 μg·kg−1·day−1 ip) or AVE-0991 (576 μg·kg−1·day−1 ip) on proteinuria, vascular responsiveness of isolated carotid and renal artery ring segments and mesenteric bed to vasoactive agonists, and cardiac recovery from ischemia-reperfusion in streptozotocin-treated rats (diabetes). Animals were killed 4 wk after induction of diabetes and/or treatment with ANG-(1–7) or AVE-0991. There was a significant increase in urine protein (231 ± 2 mg/24 h) in diabetic animals compared with controls (88 ± 6 mg/24 h). Treatment of diabetic animals with ANG-(1–7) or AVE-0991 resulted in a significant reduction in urine protein compared with vehicle-treated diabetic animals (183 ± 16 and 149 ± 15 mg/24 h, respectively). Treatment with ANG-(1–7) or AVE-0991 also prevented the diabetes-induced abnormal vascular responsiveness to norepinephrine, endothelin-1, angiotensin II, carbachol, and histamine in the perfused mesenteric bed and isolated carotid and renal arteries. In isolated perfused hearts, recovery of left ventricular function from 40 min of global ischemia was significantly better in ANG-(1–7)- or AVE-0991-treated animals. These results suggest that activation of ANG-(1–7)-mediated signal transduction could be an important therapeutic strategy to reduce cardiovascular events in diabetic patients.
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Lu, Yu, Wei Wu, and Ke-yi Wang. "High-Speed Transmission and Mass Data Storage Solutions for Large-Area and Arbitrarily Structured Fabrication through Maskless Lithography." Journal of Electrical and Computer Engineering 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/6074791.
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This paper presents the implementation aspects and design of high-speed data transmission in laser direct-writing lithography. With a single field programmable gate array (FPGA) chip, mass data storage management, transmission, and synchronization of each part in real-time were implemented. To store a massive amount of data and transmit data with high bandwidth, a serial advanced technology attachment (SATA) intellectual property (IP) was developed on Xilinx Virtex-6 FPGA. In addition, control of laser beam power, collection of status read back data of the lithography laser through an analog-to-digital converter, and synchronization of the positioning signal were implemented on the same FPGA. A data structure for each unit with a unique exposure dose and other necessary information was established. Results showed that the maximum read bandwidth (240 MB/s) and maximum write bandwidth (200 MB/s) of a single solid-state drive conform to the data transmission requirement. The total amount of data meets the requirement of a large-area diffractive element approximately 102 cm2. The throughput has been greatly improved at meters per second or square centimeter per second. And test results showed that data transmission meets the requirement of the experiment.
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Vatolin, Sergei, James G. Phillips, Shravya Govindgari, Dale Grabowski, Yvonne Parker, Daniel Lindner, Claudiu Cotta, and Frederic J. Reu. "A Novel in Vitro Three Organ System Assay Identifies a Small Molecule Ubiquitin Analog with in Vivo Activity Against Myeloma." Blood 124, no. 21 (December 6, 2014): 2085. http://dx.doi.org/10.1182/blood.v124.21.2085.2085.
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Abstract Taking a mechanistically unbiased approach to the discovery of new myeloma drugs we developed a three organ system assay that selected anti-myeloma compounds from a primary 30,000 small molecule ATP-based screen in one sandwich setup for tolerability by normal bone marrow, stability towards liver enzymes, and activity in the context of cell barriers, bone marrow stromal support, and short, kidney-clearance-like exposure (fig.1). The most promising compound (CCF642) emerging from this test had IC50s around 500 nM in all 8 MM cell lines tested including a proteasome inhibitor refractory line while the IC50 was not reached in 5 healthy bone marrow samples at doses up to 6750 nM. Similar sensitivity as in MM was seen in 7 lymphoma cell lines. Investigation of its mechanism of action revealed that CCF642 immediately stimulates protein ubiquitination which is followed by degradation of major myeloma survival factors (c-MYC, IRF4, NF-κB) and apoptosis, while normal bone marrow cells increase ubiquitination to a much lesser degree and only transiently without undergoing cell death. Experiments with an active biotinylated analog showed that it preferentially enters myeloma cells with cytoplasmic accumulation and over 10-fold lower entry into normal bone marrow. Immunoblots revealed that it becomes covalently attached to proteins in a time- and distribution pattern that parallels ubiquitination responses. In vitro, it bound to ubiquitin activating enzyme UBA1 at the active site cysteine in a similarly stable and reversible way as ubiquitin. Selective alkylation of cysteine sulfhydryl groups inhibited binding of biotinylated CCF642 to UBA1, while addition of ATP and ubiquitin led to its dissociation from UBA1. CCF642 may therefore at least in part act as a small molecule ubiquitin analog. Accordingly CCF642 binding to target proteins of UBA1 containing HeLa fraction II was increased by addition of ATP and blocked in the presence of EDTA. Injected twice a week IP at 30mg/kg it suppressed systemically engrafted luciferase expressing 5TGM1 mouse myeloma cells in syngeneic mice comparable to bortezomib given at the MTD for this mouse strain (0.5mg/kg SC twice a week) with equal prolongation of survival. Results support use of our sandwich assay to select myeloma drug candidates for in vivo testing and reveal a new UBA1 interacting small molecule ubiquitination enhancer with promise for clinical translation. Figure 1: Sandwich Three Organ System Assay Figure 1:. Sandwich Three Organ System Assay Disclosures No relevant conflicts of interest to declare.
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Culler, Michael D., Stéphane Milano, Thomas Delale, Michel Ovize, Aart Jan van der Lelij, and David R. Clemmons. "AZP-3404, a Peptide Analog of IGFBP-2, Induces Weight Loss and Improves Glucose Metabolism in Leptin-Resistant db/db Mice." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A318. http://dx.doi.org/10.1210/jendso/bvab048.648.
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Abstract Insulin-like growth factor binding protein-2 (IGFBP-2) has been demonstrated to be a key mediator of the peripheral metabolic actions of leptin. The metabolic activity of IGFBP-2 is independent of IGF1 binding, and can be localized to a unique heparin-binding domain (HBD-1) within its structure. AZP-3404 is a 9-amino acid analog of the IGFBP-2 HBD-1 that reproduces the activity of IGFBP-2 on adipocyte and osteoblast differentiation. In addition, AZP-3404 has been demonstrated to increase glucose uptake by differentiated mouse myotubes in vitro, and to increase glucose disposal following an intraperitoneal glucose tolerance test (IPGTT) in leptin-deficient ob/ob mice. In the present study, we hypothesized that AZP-3404 should be able to improve metabolic regulation in the db/db mouse, which is leptin-resistant due to a mutation in the leptin receptor, and, as a result, is also IGFBP-2 deficient. Following pre-treatment with vehicle for 1 week to establish a baseline, 9-week old male db/db mice were treated with either vehicle or AZP-3404 at doses of 1, 3 or 6 mg/kg, sc, bid (n=10/group) for 8 weeks. At the initiation of treatment, the mice weighed an average of 39.7 + 0.3 grams, and after 8 weeks, vehicle-treated mice had gained an average 8.2 + 1.6 grams of body weight. Mice treated with AZP-3404 displayed a progressive decrease in body weight gain that began after 2 weeks and that continued through the 8 weeks of treatment, ultimately resulting in less than 50% of the weight gain observed in the vehicle-treated mice, and without an apparent change in food intake. To assess the impact on glucose disposal, after both 4 and 8 weeks of treatment, and following an overnight fast, the mice were administered an IPGTT (blood glucose measured 0, 30, 60, 90, 120 and 240 minutes post-ip injection of 1 g glucose/kg). By 4 weeks of treatment, a significant increase in glucose disposal was observed in mice treated with the 6 mg/kg dose of AZP-3404 (AUC glucose decreased by 28.7%) versus vehicle-treated controls. By 8 weeks of treatment, all three doses produced similar increases in glucose disposal (AUC glucose decreased by 18.8, 21.4 and 23.1% with 1, 3 and 6 mg/kg AZP-3404, respectively) versus vehicle controls. Correspondingly, 4-hour fasted plasma insulin was decreased by 54, 48 and 52%, and the HOMA measure of insulin resistance was decreased by 55, 52 and 67%, in mice treated for 8 weeks with 1, 3 and 6 mg/kg AZP-3404, respectively, as compared with vehicle-treated mice. These results, demonstrating both improved glucose metabolism and decreased body weight gain in the leptin-resistant db/db mouse, further confirm the ability of AZP-3404 to reproduce the metabolic activity of IGFBP-2, and support the development of AZP-3404 as a novel therapy for disease states characterized by insulin resistance and/or obesity.
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Loh, Bryan, Kevin Koo, Ming Han Lincoln Liow, Winston Shang Rong Lim, Chong Zheng Ng, and Inderjeet Rikhraj. "Scarf and Weil osteotomy for symptomatic hallux valgus does not fully remove second toe residual metatarsalgia." Foot & Ankle Orthopaedics 3, no. 3 (July 1, 2018): 2473011418S0032. http://dx.doi.org/10.1177/2473011418s00325.
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Category: Bunion Introduction/Purpose: Patients with hallux valgus (HV) often experience concurrent second toe metatarsalgia due to altered forefoot biomechanics. Additional second toe Weil osteotomy has been performed to reduce transfer metatarsalgia as some studies have highlighted the presence of second toe pain after isolated HV correction. 1, 2 There is a paucity of literature evaluating residual second toe pain after these procedures . We hypothesize that combined Scarf/Weil osteotomy will result in less residual second toe pain while achieving good functioning outcome. The aim of this study was to evaluate the presence of second toe pain after isolated scarf osteotomy versus combined Scarf/Weil osteotomy. Methods: Between January 2007 and June 2012, 439 patients underwent a scarf osteotomy for symptomatic hallux valgus at a tertiary hospital. Patients who underwent isolated scarf osteotomy were matched 1:1 to patients who had both Scarf and second toe Weil osteotomy. The following functional outcome scores were prospectively collected preoperatively and postoperatively at 6 and 24 months: American Orthopaedic Foot and Ankle Society (AOFAS) Hallux Metatarsophalangeal-Interphalangeal (MTP-IP) Scale, Visual Analog Scale (VAS), SF36-Physical Component Score (PCS) and Mental Component Score (MCS). Radiological outcomes such as the Hallux Valgus Angle (HVA) and Intermetatarsal Angle (IMA) were measured. Statistical analysis was performed using SPSS® 20.0 and significance was defined as a p-value = 0.05. The Student’s unpaired t-test was used to compare the radiological and functional outcomes between the two groups of patients, while the paired t-test was used to analyze improvement in pre- and postoperative outcomes within each group. Results: 94.4% of the patients were female and no difference in BMI. In the Scarf/Weil group, the HVA and IMA improved by 21.2 ± 10.2 and 8.2 ± 4.7 degrees respectively (both P<0.001). At 2 years, the AOFAS-hallux score improved by 26.6 ± 20.9 (p=0.034), AOFAS-second toe by 29.3 ± 20.9, VAS-hallux by 3.1 ± 3.4 (p<0.001), VAS-second toe by 3.6 ± 3.2 (p<0.001). In the Scarf group, the HVA and IMA improved by 17.1 ± 8.0 and 5.8 ± 4.3 degrees respectively (both p<0.001). At 2 years, the AOFAS-hallux score improved by 32.2 ± 21.2 (p=0.034), AOFAS-second toe by 13.0 ± 16.3 (p <0.001), VAS-hallux by 4.4 ± 3.3 (p<0.001), VAS-second toe by 1.2 ± 2.4 (p<0.001). Conclusion: A significant finding is that at 6 months and 2 years, the VAS-2nd toe score in the isolated Scarf group was 1 ± 0 point lower than the other group (p<0.001). All other functional outcome scores were comparable between the two groups at 6 months. Our findings suggest that shortening second toe Weil osteotomy for large HV deformity may not fully resolve second toe metatarsalgia in the short-term, providing useful information for preoperative counselling.
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Bah, Dr Adama, Harine Abdel Aziz Garba, Ramadhane Bouchrane, Laurine Marlyse Adogle, Vanessa Lienou Tagne, Aissata Tata Kante, Sira Tall, Moustapha Niasse, and Saïdou Diallo. "SAPHO Syndrome: About an Observation and Review of the Literature." SAS Journal of Medicine 6, no. 9 (September 24, 2022): 624–27. http://dx.doi.org/10.36347/sasjm.2022.v08i09.008.
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Introduction: SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) is autoinflammatory rheumatism of the spondyloarthritis group. It is rare, it prevalence is 1/10000 inhabitants. The average age at diagnosis is 38 years, with no gender predominance, first described by Chamot and colleagues in 1987. Objective: To present observation and review of the literature on SAPHO syndrome which is rarely diagnosed in our daily practice. Observation: This was a 28 year old female patient, Senegalese, living in Dakar, followed in obstetrics gynecology for the desire of maternity, the family context of sickle cell disease who consulted for diffuse mechanical and articular inflammatory pains involving the proximal interphalangeal (IPP) of the left 5th toe, the left shoulder, the sternocostal and dorsolumbar joints evolving for 3 years. The clinical examination found: A painful swelling with a visual analog scale (VAS) of 6/10 of the right sternocostal joint and of the interphalangeal joint (IP) of the right hallux, diffuse acne, no palmoplantar pustulosis, no psoriasis, no gluteal or talalgia. The biology shows an inflammatory syndrome (VS at 37 mn at the 1st hour and CRP at 41mg/l), a decrease of 25-OH-Vitamin D3 at 22 ng/ml (N: 25-30 ng/ml), the positive latex test, Ac anti-CCP: 43 IU/ml (N < 5 IU/ml), positive Ac anti-HBc , Ac anti HBs > 1000 IU/l on the other hand blood calcium, blood phosphorus, G6PD, PTH, TSH us, free T4, anti ECT Ac, HLA-B27 Ag with no particularities. The scintigraphy showed hyper fixation of the right 1st toe, sacroiliac joints, dorsolumbar spine, left shoulder, manubrium sternal junction, and bilateral sternoclavicular junction realizing a classical bull horn image in SAPHO syndrome. Because of this clinical and paraclinical manifestation helped by the 1994 diagnostic criteria of Kahn at 1/3 (chronic joint involvement associated with severe acne), the SAPHO syndrome was retained and the treatment instituted after the normal pre-therapeutic analysis and systematic deworming was: Salazopyrine 2000mg/day (dosage reached by increments of 500 mg/week); Uvedose (vitamin D3 ) 100000 IU / month; bisphosphonates 70 mg /week and paracetamol + codeine 1g x 2/day as needed for 3 months with a favorable follow-up by the regression of signs (pain VAS at 2/10). Conclusion: The SAPHO syndrome is the prerogative of the young adult subject, bone scintigraphy is very valuable for its diagnosis, its better knowledge would avoid diagnostic and therapeutic erratic. Keywords: SAPHO syndrome, bone scan, Dakar, Senegal.
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Dasmahapatra, Girija, Dmitry Lembersky, Jonathan W. Friedberg, Richard I. Fisher, Paul Dent, and Steven Grant. "Histone Deacetylase Inhibitors Potentiate the Lethality of the Irreversible Proteasome Inhibitor Carfilzomib In Mantle Cell Lymphoma Cells In Vitro and In Vivo." Blood 116, no. 21 (November 19, 2010): 3938. http://dx.doi.org/10.1182/blood.v116.21.3938.3938.
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Abstract Abstract 3938 The proteasome inhibitor (PI) bortezomib (BTZ) is approved for the treatment of refractory mantle cell lymphoma (MCL). However, BTZ achieves clinical responses in only 40% of refractory MCL patients, justifying the search for newer proteasome inhibitors and/or the development of rational combination regimens. Recently we reported that the irreversible PI carfilzomib (CFZ) interacted synergistically with the histone deacetylase inhibitor (HDACI) vorinostat (Vor) in diverse DLBCL cells including GC (germinal center) and ABC (activated B-cell) sub-types both in vitro and in vivo. (Dasmahapatra et al., Blood 2010; 115:4478-87, 2010). Moreover, regimens combining PIs with histone deacetylase inhibitors (HDACIs) have shown promising activity in multiple myeloma. Collectively, these preclinical and clinical findings raise the possibility combining CFZ with HDACIs might be an effective strategy in MCL. To test this possibility, CFZ/HDACI interactions were investigated in diverse MCL cell types, including those resistant to BTZ. Simultaneous treatment (24-48 hr) with sub-lethal CFZ concentrations (2-5 nM) and minimally toxic concentrations of vorinostat (Vor; 1–2 μM), SNDX-275 (1-2 μM) or SBHA (30-50 μM) strikingly increased apoptosis (manifested by annexin V, 7-AAD or TUNEL positivity) in various MCL lines, including Granta, HF-4B, Rec-1, JVM-2, MINO and JVM-12. Interactions were highly synergistic, as determined by Median Dose Effect analysis, with Combination Index values significantly less than 1.0. HDACIs also interacted synergistically with ONX 0912 (formerly PR-047), an orally bioavailable analog of CFZ. The activity of these regimens was associated with a sharp increase in caspase-3 activation, PARP cleavage, mitochondrial damage (loss of ΔΨm, cytoplasmic cytochrome c release), and induction of p21CIP1. Combined CFZ/Vor exposure also markedly induced phosphorylation of JNK and c-Jun, down-regulation of phospho-AKT and phospho-ERK1/2, and induction of γH2A.X, a marker of double-stranded DNA breaks. In contrast to single agent administration (48 hr), where the percentage of apoptotic cells gradually declined following drug washout over the ensuing 4–5 days, extensive apoptosis (e.g. > 80%) persisted in cells co-treated with CFZ/Vor. Combined treatment of MCL cells with CFZ/Vor induced more sustained inhibition of chymotrypsin-like (CT-L) proteasome activity than that observed following single-agent treatment. CFZ alone exhibited partial cross resistance to BTZ- resistant Granta cells (GR-25BR). However, co-administration of CFZ/Vor resulted in the highly synergistic induction of apoptosis in BTZ-resistant cells. Genetic interruption of JNK signaling (e.g., via shRNA knockdown) significantly attenuated CFZ/Vor-mediated apoptosis, indicating that JNK activation plays a functional role in the lethality of this regimen in MCL cells. Combined treatment with CFZ and HDACIs induced G2M arrest in both parental and BTZ-resistant GR-25BR cells, an effect that was not modified by genetic interruption of JNK signaling. The CFZ/Vor regimen also strikingly induced apoptosis in 3 primary human MCL specimens, in contrast to the minimal lethality exhibited toward normal CD34+ cells as previously described (Blood; 115:4478-87, 2010). Finally, in vivo administration of CFZ (IV BIW) and Vor (IP TIW) to Beige-nude-XID mice (NIH-III) inoculated in the flank with Granta cells substantially suppressed tumor growth compared to single agent treatment. Collectively, these findings indicate that combining HDACIs with CFZ synergistically induces apoptosis in MCL cells through a JNK-dependent mechanism in association with G2M arrest and the induction of DNA damage. They also suggest that this strategy, which is active against diverse MCL cell types, including BTZ-resistant and primary MCL cells, and which displays in vivo activity, warrants further examination in MCL. Accordingly, plans for a Phase I CFZ/HDACI trial in NHL, including MCL patients, are currently underway. Supported by Lymphoma SPORE 1P50 CA130805. Disclosures: Friedberg: Genentech: Honoraria.
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Sun, Guohui, Tengjiao Fan, Xiaodong Sun, Yuxing Hao, Xin Cui, Lijiao Zhao, Ting Ren, Yue Zhou, Rugang Zhong, and Yongzhen Peng. "In Silico Prediction of O6-Methylguanine-DNA Methyltransferase Inhibitory Potency of Base Analogs with QSAR and Machine Learning Methods." Molecules 23, no. 11 (November 6, 2018): 2892. http://dx.doi.org/10.3390/molecules23112892.
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O6-methylguanine-DNA methyltransferase (MGMT), a unique DNA repair enzyme, can confer resistance to DNA anticancer alkylating agents that modify the O6-position of guanine. Thus, inhibition of MGMT activity in tumors has a great interest for cancer researchers because it can significantly improve the anticancer efficacy of such alkylating agents. In this study, we performed a quantitative structure activity relationship (QSAR) and classification study based on a total of 134 base analogs related to their ED50 values (50% inhibitory concentration) against MGMT. Molecular information of all compounds were described by quantum chemical descriptors and Dragon descriptors. Genetic algorithm (GA) and multiple linear regression (MLR) analysis were combined to develop QSAR models. Classification models were generated by seven machine-learning methods based on six types of molecular fingerprints. Performances of all developed models were assessed by internal and external validation techniques. The best QSAR model was obtained with Q2Loo = 0.83, R2 = 0.87, Q2ext = 0.67, and R2ext = 0.69 based on 84 compounds. The results from QSAR studies indicated topological charge indices, polarizability, ionization potential (IP), and number of primary aromatic amines are main contributors for MGMT inhibition of base analogs. For classification studies, the accuracies of 10-fold cross-validation ranged from 0.750 to 0.885 for top ten models. The range of accuracy for the external test set ranged from 0.800 to 0.880 except for PubChem-Tree model, suggesting a satisfactory predictive ability. Three models (Ext-SVM, Ext-Tree and Graph-RF) showed high and reliable predictive accuracy for both training and external test sets. In addition, several representative substructures for characterizing MGMT inhibitors were identified by information gain and substructure frequency analysis method. Our studies might be useful for further study to design and rapidly identify potential MGMT inhibitors.
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Minuesa Dinares, Gerard, Steven K. Albanese, Arthur Chow, Alexandra Schurer, Sun Mi Park, Christina Z. Rotsides, James Taggart, et al. "Small-Molecule Targeting of Musashi RNA-Binding Activity in Acute Myeloid Leukemia." Blood 132, Supplement 1 (November 29, 2018): 428. http://dx.doi.org/10.1182/blood-2018-99-118745.
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Abstract RNA-binding proteins (RBPs) play critical roles in cell homeostasis by controlling gene expression post-transcriptionally, contributing to mRNA processing events (splicing, polyadenylation, localization, stability, export and translation). The involvement of RBPs to tumorigenesis, through genetic perturbation or epigenetic dysregulation, has been found in a variety of human cancers. The RBP MUSASHI-2 (MSI2) contributes to the pathogenesis of a spectrum of solid tumors and hematologic malignancies and predicts a worse clinical outcome in patients with myeloid and acute lymphoblastic leukemia (MDS, AML and ALL). Thus, MSI2 has been proposed as a putative biomarker for diagnosis as well as a potential therapeutic target for AML. However, there are currently no specific inhibitors for MSI. Previous work from our lab reported a Fluorescent Polarization (FP) screen with 6,208 compounds identifying small-molecules with MSI RNA-binding inhibition activity. Here, we characterize Ro 08-2750 (Ro), best FP screen hit, as a MSI RNA-competitive inhibitor. Electrophoresis Mobility Shift Assays (EMSA) demonstrated Ro inhibition of MSI2-RNA complexes formation. MicroScale Thermophoresis (MST) interaction studies showed that the compound interacts with MSI2 full-length and RNA-Recognition Motif 1 (RRM1) with μM affinity and with nearly 20-fold lower KD to an RBP control (SYNCRIP). We obtained the crystal structure of MSI2 RRM1 at 1.7Å and docking and mutagenesis validation confirmed K22, F66, F97 and R100 as crucial binding residues in the RNA-binding pocket. To further prove structure activity relationship, we used two chemical analogs: Ro-OH, an alcohol derivative of the Ro's aldehyde, showed 10-fold reduced activity and Ro-NGF, containing the Ro isoalloxazine scaffold, showed no binding or activity in vitro. Of note, in proliferation assays Ro EC50 was 2.6±0.1 μM in MLL-AF9 bone marrow cells and an average of 8.4±1.1 μM in MOLM13 and K562 human AML cells, whereas RoOH and RoNGF showed 10-fold or >50 μM EC50, respectively. Ro significantly reduced binding of MSI2 to its mRNA targets (such as cMYC, CDKN1A or SMAD3) in an RNA-IP and a direct effect in their protein translation in human leukemia cells. RNA-sequencing of 4h Ro treated MOLM13 and K562 AML cells resulted in gene expression changes that enriched for the gene expression profiling after shRNA mediated depletion of MSI2 in CML-BC and AML cell lines. Ro demonstrated a significant therapeutic index abolishing MLL-AF9+ BM colony formation at concentrations that did not affect the plating efficiency of normal Lin-Sca+cKit+ (LSK) cells. Similarly, Ro demonstrated differential sensitivity in three AML patient samples colony formation compared to normal human CD34+ cord blood cells. Finally, we sought to determine Ro in vivo activity by using an aggressive murine MLL-AF9 murine leukemia model. Acute treatment (4h and 12hr) with 13.75 mg/kg Ro in DMSO reduced c-KIT protein abundance and intracellular c-MYC. Administration of the same Ro dose every 3 days was well tolerated and showed a significant reduction in spleen weights, white blood cell counts and c-MYC levels compared to the controls. These data provide the feasibility that targeting MSI in vivo could have therapeutic efficacy in AML. This study identifies and characterizes Ro 08-2750 as a compound selectively inhibiting the oncogenic RNA-binding activity of MSI in myeloid leukemia. Ro targeting an RRM motif to block RNA activity represents a valuable proof of concept for the general inhibition of these class of RNA regulators. Overall, we provide a framework to identify and test novel RBP inhibitors thus validating this class of proteins as chemically "druggable" novel therapeutic targets in cancer. Disclosures Chodera: Schrödinger: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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Turcza, Pawel, and Mariusz Duplaga. "Low-Power Low-Area Near-Lossless Image Compressor for Wireless Capsule Endoscopy." Circuits, Systems, and Signal Processing, August 27, 2022. http://dx.doi.org/10.1007/s00034-022-02149-6.
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AbstractThe paper presents the concept of a low-power, low-area, near-lossless image compressor for resource-constrained devices such as wireless capsule endoscopy (WCE). The compressor directly processes the raw data from the Bayer Color Filter Array (CFA) imager to avoid the high cost of color interpolation. To improve the efficiency of the compressor in terms of energy consumption, silicon area and compression ratio, the main part of the compressor, i.e., the entropy encoder, uses the existing correlations between the color components of a captured CFA image. The proposed image compressor requires only 12.4% of the memory needed by other high-quality CFA compressors based on the JPEG-LS standard. Despite this significant reduction in memory size, the proposed image compressor outperforms other state-of-the-art coding schemes on capsule endoscopy images. At the same time, it offers only slightly lower performance on standard test images. The proposed image compressor has been implemented as an intellectual property (IP) core using two different low-cost CMOS processes. The design, implemented in UMC 180 nm CMOS process, requires a very low silicon area (534 $$\times $$ × 426 $$\upmu $$ μ m$$^{2}$$ 2 ) and consumes very low energy (22 $$\upmu $$ μ J per a single 512 $$\times $$ × 512 image frame). Even higher energy efficiency (12 $$\upmu $$ μ J per the same image frame) has the IP core implemented in the TSMC 130 nm CMOS process. Both of the selected technologies are low-cost and well-suited to implement a radio frequency transmitter and a low-power successive approximation register analog-to-digital converter in addition to the compressor to provide a cost-effective System on Chip for resource-constrained devices like WCE or wireless camera sensor network.
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Uriarte, SA, H. Grönlund, A. Wintersand, J. Bronge, and J. Sastre. "Clinical and immunologic changes due to subcutaneous immunotherapy with cat and dog extracts using an ultrarush up-dosing phase: a real-life study." Journal of Investigational Allergology and Clinical Immunology 32, no. 2 (November 25, 2020). http://dx.doi.org/10.18176/jiaci.0656.
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Objective: We aimed to evaluate the efficacy of and immunologic changes caused by subcutaneous immunotherapy (SCIT) in patients with allergy to cat and dog. Methods: Patients presenting rhinitis and/or asthma with allergy to cat or dog from a previous safety study were included. All had specific IgE to cat and/or dog. Using an infusion pump (IP), SCIT maintenance dose was administered over one 4-hour session, followed by monthly administration over 6 months. Data were gathered on clinical outcomes, pulmonary function, FeNO, rhinitis and asthma symptoms, quality of life (QoL), asthma control test (ACT), and symptom visual analog scale (VAS) at baseline and then at 1, 3, and 6 months. Specific IgE and IgG antibody responses to different cat and dog allergens were determined. Results: Sixty-one patients having a mean age of 35.6 ± 9.7 years were included, 40 of whom underwent cat SCIT. A significant improvement was observed in rhinitis and asthma symptoms and in QoL, use of medication, VAS, and ACT at 1 month; these improvements persisted at month 6. Clinical improvement with cat extract was significantly higher than with dog. An increase of >0.9 in ESPRINT-15 health-related quality of life in allergic rhinitis) was observed in 49.09% of patients, and 58.18% showed an increase of >0.5 in AQLQ(asthma quality of life questionnaire), at month 6, both differences indicating the minimal important difference. A significant increase was observed in specific IgG and IgE to different allergens at 3 and/or 6 months. Conclusions: Ultrarush SCIT with cat and dog extracts has substantial clinical value in many patients.
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Mukohda, Masashi, Stella-Rita C. Ibeawuchi, Chunyan Hu, Jing Wu, Ko-Ting Lu, Debbie R. Davis, Deng-Fu Guo, Kamal Rahmouni, Frederick W. Quelle, and Curt D. Sigmund. "Abstract 124: RhoBTB1, a Novel PPARγ Target Gene, Rescues Hypertension and Vascular Dysfunction Caused by PPARγ Dysfunction." Hypertension 70, suppl_1 (September 2017). http://dx.doi.org/10.1161/hyp.70.suppl_1.124.
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We reported that mice (S-DN) expressing dominant-negative peroxisome proliferator-activated receptor gamma (PPARγ) in smooth muscle cells (SMC) are hypertensive and exhibit impaired vascular relaxation due to increased RhoA/Rho kinase (ROCK) activity, and display reduced expression of a novel PPARγ target gene, RhoBTB1. We hypothesize that RhoBTB1 plays a protective role in vascular function and that the function of RhoBTB1 is disrupted in S-DN mice. To test this, we generated double transgenic mice (termed S-RhoBTB1) with tamoxifen-inducible, Cre-dependent expression of RhoBTB1 in SMC. S-RhoBTB1 mice were crossed with S-DN to produce mice (S-DN/S-RhoBTB1) in which tamoxifen-treatment (75 mg/kg, ip, 5 days) restored RhoBTB1 expression in aorta to normal. Thoracic aorta and basilar artery from S-DN showed severely impaired vasodilation to acetylcholine (ACh) and sodium nitroprusside, which was reversed by restoration of RhoBTB1 in SMC (Aorta, 46±5 vs 80±2% ACh-induced relaxation, p<0.01, n=6-9). Replacement of RhoBTB1 also reversed the hypertensive phenotype and aortic stiffness observed in S-DN mice within 1 week of treatment (Radiotelemetry SBP, 141±6 vs 124±3 mmHg, p<0.01, n=8-10; Aortic Pulse Wave Velocity, 3.8±0.2 vs 2.5±0.1 mm/ms, p<0.01, n=11-13). Increased phosphorylation of myosin phosphatase targeting protein was preserved in both S-DN and S-DN/S-RhoBTB1 aorta, suggesting that restoration of RhoBTB1 did not affect increased RhoA/ROCK activity (p<0.01, n=6). A phosphodiesterase (PDE) 5 inhibitor, Zaprinast improved vasodilation in S-DN (p<0.01, n=8). Consistent with this, a cGMP analog that is resistant to PDE hydrolysis, 8-pCPT-cGMP, induced equivalent relaxation in S-DN and non-transgenic mice (n=4), while S-DN exhibited impaired relaxation induced by PDE-sensitive 8-Bromo-cGMP (p<0.01, n=7). PDE activity was increased in S-DN aorta and was reduced to normal levels in S-DN/S-RhoBTB1 (p<0.01, n=6). We conclude: a) loss of RhoBTB1 function explains the vascular dysfunction and hypertension observed in response to interference with PPARγ in smooth muscle, b) DN PPARγ in SMC causes vascular dysfunction via promoting PDE activity, and c) restoration of RhoBTB1 in SMC facilitates vasodilatation by normalizing PDE activity.
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Fitratin, Nur Hikmah, Dyah Ayu Fajarianingtyas, and Henny Diana Wati. "PENGARUH PENGAJARAN REMEDIAL MENGGUNAKAN STRATEGI ANALOGI TERHADAP MISKONSEPSI IPA." LENSA (Lentera Sains): Jurnal Pendidikan IPA 8, no. 1 (June 24, 2018). http://dx.doi.org/10.24929/lensa.v8i1.32.
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This research aims to find out 1) Remedial teaching implementation using analogy strategy to VII grade students of SMP Negeri 1 Saronggi, 2) Differences of IP science misconception between remedial teaching using analogy strategy and remedial teaching using direct learning strategy, 3) Improvement of student learning outcomes of grade VII after using remedial teaching using analogy strategies. This type of research is quantitative research using quasi experimental design. The sampling technique used cluster random sample technique. Technique of collecting data using test instrument with CRI and non test method. The data were analyzed using Mann-Whitney test. The results showed 1) The implementation of remedial teaching using analogy strategy of 98% with very good category and the implementation of remedial teaching using direct learning strategy of 91% with very good category. 2) Mann-Whitney test result of 0,017 indicating that there is difference of science misconception between remedial teaching using strategy analogies with remedial teaching using direct learning strategy. 3) The result of gain score in the experimental class is 0,71 with the high category, while the control class is 0,52 with the medium category. Remedial teaching using analogy strategies can be used to address misconceptions in students.