Negative Gates Research Articles

Design of ternary logic gates and buffer- based memory cell in nanoelectronics

ABSTRACT Using multi-valued circuits reduce the number of connections on a chip and the area of the chip and power consumption in the connections. . In this paper, a new structure of single-source logic gates, AND, OR and BUFFER were designed using CNFET. In the new design, AND and OR have directly been designed instead of NAND and NOR, because in previous designs, NAND and NOR were needed to achieve AND and OR. Also, due to the fact that PT, NT inverters and positive, negative logic gates have been used, it is possible to adjust the voltage of the switch to achieve a better noise margin. Also, with the proposed ternary BUFFER, a single-source ternary memory cell was designed, with the advantages of a smaller number of transistors and the need for only a single line for reading and writing, which greatly reduces the number of interconnections. Since the number of interconnections in the memory array increases tremendously, this design significantly reduces the number of connections in the memory array. The simulation results using Hspice software and the Stanford CNT-32 nm model indicate the correct operation of the circuits and represent the improved 70% and 90% in PDP of gates compared with the state-of-art work.

Syncytia formation by SARS-CoV-2-infected cells.

Severe cases of COVID‐19 are associated with extensive lung damage and the presence of infected multinucleated syncytial pneumocytes. The viral and cellular mechanisms regulating the formation of these syncytia are not well understood. Here, we show that SARS‐CoV‐2‐infected cells express the Spike protein (S) at their surface and fuse with ACE2‐positive neighboring cells. Expression of S without any other viral proteins triggers syncytia formation. Interferon‐induced transmembrane proteins (IFITMs), a family of restriction factors that block the entry of many viruses, inhibit S‐mediated fusion, with IFITM1 being more active than IFITM2 and IFITM3. On the contrary, the TMPRSS2 serine protease, which is known to enhance infectivity of cell‐free virions, processes both S and ACE2 and increases syncytia formation by accelerating the fusion process. TMPRSS2 thwarts the antiviral effect of IFITMs. Our results show that SARS‐CoV‐2 pathological effects are modulated by cellular proteins that either inhibit or facilitate syncytia formation.

One dimensional electron gas at the LaAlO3/SrTiO3 interface and its transport properties

Quasi-one-dimensional electron gases (q1DEGs) have been obtained by fabricating LaAlO3 nanowires, using the technique of electrostatic spinning plus post annealing, above TiO2-terminated SrTiO3 substrate. The q1DEG exhibits an electronic transport behavior of variable range hopping with the one dimension characteristic. Visible light illumination produces a strong effect on transport process, depressing the resistance of the q1DEG by a factor up to 8. As expected, gating effect is weak at relative high temperatures, ∼3.2% at 150 K and 1.5% at 300 K under a back gate of 200 V. Aided by light illumination, however, the gating effect is 35-fold amplified, and the resistance increases under not only negative gates but also positive gates, different from the normal gating effect without illumination. Possible explanations for these phenomena are given.

Phospho-Specific Flow Cytometry of Fixed Whole Blood Demonstrates In Vivo FLT3 Inhibition in Circulating Leukemic Blasts During AC220 Therapy and Accurately Detects the Development of Therapeutic Resistance,

Abstract 3502 Background:AC220 (quizartinib) is a potent, highly selective inhibitor of FLT3, c-KIT, and c-FMS tyrosine kinases with promising clinical activity in AML, particularly among patients with FLT3 internal tandem duplication mutations (FLT3-ITD). However, direct confirmation of biochemical FLT3 inhibition in AML blasts in vivo by AC220 has not been previously described. We report separately that phospho-ribosomal protein S6 (pS6) by flow cytometry provides a sensitive and dynamic readout of FLT3 kinase activity during FLT3 inhibitor therapy. S6 is a downstream target of the PI3 kinase/mammalian target of rapamycin (mTOR) pathway, is constitutively phosphorylated in nearly all FLT3-ITD+ samples, and its phosphorylation shows dynamic changes in response to FLT3 ligand (FL) or FLT3 inhibitors. We hypothesized that reductions in S6 phosphorylation by flow could serve as a biomarker for FLT3 inhibition and predict response and/or resistance to AC220. Methods:Serial peripheral blood samples were collected during a phase II AC220 clinical trial (Cortes, et al. EHA 2011, abstract #1019). Samples were aliquoted into FACS tubes within four hours of collection and a subset was exposed to signaling inhibitors (ex vivo AC220, rapamycin × 30 min.) or activators (phorbol ester/PMA or FL × 10 min.) to establish dynamic controls. Following incubation, samples were formaldehyde-fixed and red cells were lysed with the permeabilizing agent triton X-100. Samples were stored at −20C in glycerol medium. Samples from all time points were simultaneously thawed, denatured with ice-cold methanol, and stained with a single antibody cocktail. Blasts were identified by using CD45 and side scatter (SSC) and confirmed by expression of multiple surface markers (CD33, CD34, CD117, HLA-DR, etc.). Positive and negative pS6 gates were created by comparing blasts in stimulated and unstimulated conditions and/or autofluorescence (FMO) controls. Results:6 subjects provided blood samples (5 FLT3-ITD, 1 FLT3-WT) and had evaluable peripheral blasts (>100/microliter) for pS6 monitoring. As previously described by our group and others using intracellular flow, pS6 is heterogeneous in primary AML samples and, at a basal state, frequently only demonstrable in a subset of blasts. The mean percentage of blasts demonstrating S6 phosphorylation prior to AC220 therapy was 29% (median 9.8%, range 2–97%). To quantify FLT3 kinase inhibition in vivo, we monitored pS6 prior to and following subjects’ initial dose of AC220. Samples obtained two hours following the initial dose consistently reduced the percentage of blasts with pS6 to a mean of 2.8% (median 1, range 0.02 to 11). Consistent with its long half-life, pS6 following a single dose of AC220 remained consistently and potently suppressed at trough concentration on day 2. Comparing clinical response and biochemical inhibition by AC220, all 5 subjects with marked reduction in pS6 to AC220 cleared peripheral blasts by day 29 and 3 subjects achieved marrow blasts <5%. By contrast, a FLT3-WT subject with no WBC reduction during AC220 therapy showed persistent constitutive S6 phosphorylation in FLT3-expressing cells. Re-activation of S6 phosphorylation also occurred in 2/2 FLT3-ITD+ subjects who relapsed during AC220. In both cases, we detected treatment-emergent FLT3-D835 mutations, which have been shown to confer potent in vitro resistance to AC220 (Smith, et al, AACR 2011, abstract #4737). Although S6 phosphorylation in relapsed patients’ blasts was not suppressed by additional ex vivo AC220, plasma obtained at relapse potently inhibited S6 phosphorylation in the FLT3-ITD+ cell line Molm14. Taken together, these data confirm that these subjects’ blasts show intrinsic resistance to AC220 and that drug failure was not secondary to pharmacokinetic changes over time. Conclusions:We demonstrate the feasibility and utility of intracellular flow cytometry for phospho-S6 to monitor the biochemical efficacy of FLT3 inhibitors. The potential of these methods to predict clinical response/resistance paired with the rapid turnaround time of flow cytometry suggests potential future application of this technology in the screening evaluation of patients offered novel signal transduction inhibitors. Studies correlating the magnitude of signal inhibition with IWG responses are ongoing in a larger cohort treated with AC220 and will be reported once clinical data mature. Disclosures:Carroll:TetraLogic Pharmaceuticals: Research Funding; Sanofi Aventis Corporation: Research Funding; Glaxo Smith Kline, Inc.: Research Funding; Agios Pharmaceuticals: Research Funding.

Genetic Networks Described in Stochastic Pi Machine (SPiM) Programming Language

If biological objects are created by natural selection, why are they composed of discrete modules? What has been the nature of mutations since the Darwinian epoch? This paper presents examples of genetic circuits in terms of stochastic
-calculus; a new mathematical language for nanosystems. The author used a constructor of five elements such as decay, null gate, gene product, and negative and positive gates. These primitives were applied to design genetic switches, oscillators, feedforward and feedback loops, pulse generators, memory elements, and combinatorial logics. The behaviors of those circuits were investigated – functions, such as oscillations or a spontaneous pulse generation were performed simply, flip-flops between stable states occurred in the noisy environment. The modular essence of
-calculus and the following up features of Stochastic Pi Machine (SPiM) programming language allowed us to change the topology of networks that resembled a gene exchange in nature. Other types of mutations were considered as variations in parameters. Perturbations modified system behavior in unpredictable ways that generated diversity for a possible future design by selection of appropriative variants.

Logic synthesis of a PLL phase frequency detector

The design of the phase frequency detector of the phase locked loop of the strongarm microprocessor has been designed according to an asynchronous design methodology based on negative gates. This methodology is based on a CMOS gate delay model which takes into account the delays of input inverters. The resulting phase frequency detector presents better performances than the conventional circuit used generally in phase locked loops.

Logic synthesis of race-free asynchronous CMOS circuits

A synthesis method for generating race-free asynchronous CMOS circuits that are independent of the internal and output delays is presented. The design method is based on the properties of the negative gates. An inertial delay is associated with each negative gate in a CMOS circuit. Such a gate model is quite realistic. The basic principle of the method presented is to augment and to modify the original flow table in such a way that the obtained logic diagram contains only negative gates. In addition, the synthesis method is capable of avoiding any race, and consequently any critical race or hazard. The method minimizes the number of internal variables and therefore the number of gates, providing new simple cells for fast and low-power integrated circuits.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Design of MOS networks in single-rail input logic for incompletely specified functions

If a logic gate in a logic network of MOS transistors expresses a negative function, which is a logic function that can be expressed as the complement of a disjunctive form of only noncomplemented variables, it is called a negative gate. An algorithm, DIMN, for the design of a MOS logic network with a minimum number of negative gates and irredundant connections among negative gates for a completely specified function was published by the authors in 1985. DIMN is extended here to the case of an incompletely specified function, and an example is given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Synthesis of Gate-Minimum Multi-Output Two-Level Negative Gate Networks

A negative gate is a gate which can realize an arbitrary negative function. The problem of synthesizing logical networks, with negative gates only, is important for the design of MOS LSI.

Minimal Negative Gate Networks

A negative gate is a gate that can realize an arbitrary negative function (or monotone decreasing function) and a positive gate is one that can realize an arbitrary positive function (or monotone increasing function). This paper discusses methods of realizing a given logical function or a given set of logical functions using a minimum number of negative gates alone or using a minimum number of negative and positive gates.

Gate-Interconnection Minimization of Switching Networks Using Negative Gates

In this note, we develop an algorithm to design a two-level switching network composed of negative gates with no fan-in restriction imposed on them. The resulting network is such that it minimizes the cost function h(G, 1), a monotone nondecreasing function of G and I, where G is the total number of gates and I is the total number of interconnections in the network. In other words, the earlier work is generalized so that the number of interconnections may be included in its cost criterion. The algorithm is then extended to the multiple output network design.

Synthesis of Networks with a Minimum Number of Negative Gates

In this paper we develop an algorithm to design a switching network using only gates which represent negative functions. The number of gates in the network is minimized under the conditions that 1) the network consists of two levels, and 2) no fan-in restriction on each gate is imposed.