The Immunity of Evolvable Digital Circuits to ESD Interference

With the rapid development of semiconductor technology and the increasing proliferation of emission sources,digital circuits are frequently used in harsh and hostile electromagnetic environments.Electrostatic Discharge (ESD) interferences are gradually gaining prominence,resulting in performance degradations,malfunctions and disturbances in component and/or system level applications.Conventional solutions to such problems are shielding,filtering and grounding.This paper proposes a novel Evolvable Digital Circuit (EDC) for intrinsic immunity.The key idea is motivated by the noise-robustness and fault-tolerance of the biological system.First,the architecture of the EDC is designed based on the cell structure.Then,ESD immunity tests are carried out on the most fragile element of the EDC in operation.Based on the results,fault models are also presented to simulate different functional disturbances.Finally,the immunity of the EDC is evaluated while it is exposed to a variety of simulated environments.The results which demonstrate a graceful immunity to ESD interference are presented.     

Dealing with the Evolutionary Downside of CRISPR Immunity: Bacteria and Beneficial Plasmids

The immune systems that protect organisms from infectious agents invariably have a cost for the host. In bacteria and archaea CRISPR-Cas loci can serve as adaptive immune systems that protect these microbes from infectiously transmitted DNAs. When those DNAs are borne by lytic viruses (phages), this protection can provide a considerable advantage. CRISPR-Cas immunity can also prevent cells from acquiring plasmids and free DNA bearing genes that increase their fitness. Here, we use a combination of experiments and mathematical-computer simulation models to explore this downside of CRISPR-Cas immunity and its implications for the maintenance of CRISPR-Cas loci in microbial populations. We analyzed the conjugational transfer of the staphylococcal plasmid pG0400 into Staphylococcus epidermidis RP62a recipients that bear a CRISPR-Cas locus targeting this plasmid. Contrary to what is anticipated for lytic phages, which evade CRISPR by mutations in the target region, the evasion of CRISPR immunity by plasmids occurs at the level of the host through loss of functional CRISPR-Cas immunity. The results of our experiments and models indicate that more than 10⁻⁴ of the cells in CRISPR-Cas positive populations are defective or deleted for the CRISPR-Cas region and thereby able to receive and carry the plasmid. Most intriguingly, the loss of CRISPR function even by large deletions can have little or no fitness cost in vitro. These theoretical and experimental results can account for the considerable variation in the existence, number and function of CRISPR-Cas loci within and between bacterial species. We postulate that as a consequence of the opposing positive and negative selection for immunity, CRISPR-Cas systems are in a continuous state of flux. They are lost when they bear immunity to laterally transferred beneficial genes, re-acquired by horizontal gene transfer, and ascend in environments where phage are a major source of mortality.     

Neural Tuning Functions Underlie Both Generalization and Interference

In sports, the role of backswing is considered critical for generating a good shot, even though it plays no direct role in hitting the ball. We recently demonstrated the scientific basis of this phenomenon by showing that immediate past movement affects the learning and recall of motor memories. This effect occurred regardless of whether the past contextual movement was performed actively, passively, or shown visually. In force field studies, it has been shown that motor memories generalize locally and that the level of compensation decays as a function of movement angle away from the trained movement. Here we examine if the contextual effect of past movement exhibits similar patterns of generalization and whether it can explain behavior seen in interference studies. Using a single force-field learning task, the directional tuning curves of both the prior contextual movement and the subsequent force field adaptive movements were measured. The adaptation movement direction showed strong directional tuning, decaying to zero by 90° relative to the training direction. The contextual movement direction exhibited a similar directional tuning, although the effect was always above 60%. We then investigated the directional tuning of the passive contextual movement using interference tasks, where the contextual movements that uniquely specified the force field direction were separated by ±15° or ±45°. Both groups showed a pronounced tuning effect, which could be well explained by the directional tuning functions for single force fields. Our results show that contextual effect of past movement influences predictive force compensation, even when adaptation does not require contextual information. However, when such past movement contextual information is crucial to the task, such as in an interference study, it plays a strong role in motor memory learning and recall. This work demonstrates that similar tuning responses underlie both generalization of movement direction during dynamic learning and contextual movements in both single force field and interference tasks.     

CRISPR RNA binding and DNA target recognition by purified Cascade complexes from Escherichia coli

Clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated Cas proteins comprise a prokaryotic RNA-guided adaptive immune system that interferes with mobile genetic elements, such as plasmids and phages. The type I-E CRISPR interference complex Cascade from Escherichia coli is composed of five different Cas proteins and a 61-nt-long guide RNA (crRNA). crRNAs contain a unique 32-nt spacer flanked by a repeat-derived 5′ handle (8 nt) and a 3′ handle (21 nt). The spacer part of crRNA directs Cascade to DNA targets. Here, we show that the E. coli Cascade can be expressed and purified from cells lacking crRNAs and loaded in vitro with synthetic crRNAs, which direct it to targets complementary to crRNA spacer. The deletion of even one nucleotide from the crRNA 5′ handle disrupted its binding to Cascade and target DNA recognition. In contrast, crRNA variants with just a single nucleotide downstream of the spacer part bound Cascade and the resulting ribonucleotide complex containing a 41-nt-long crRNA specifically recognized DNA targets. Thus, the E. coli Cascade-crRNA system exhibits significant flexibility suggesting that this complex can be engineered for applications in genome editing and opening the way for incorporation of site-specific labels in crRNA.     

Direct Visualization of Native CRISPR Target Search in Live Bacteria Reveals Cascade DNA Surveillance Mechanism

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Binding of FANCI-FANCD2 Complex to RNA and R-Loops Stimulates Robust FANCD2 Monoubiquitination

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热休克蛋白-多肽复合物在肿瘤和传染性疾病免疫中的作用

热休克蛋白家族中的许多成员如gp96\,HSP90\,HSP70等具有排斥和治疗肿瘤及传染性疾病的免疫原性,进一步研究发现热休克蛋白作为分子伴侣可结合细胞中的肽库,它本身没有抗原性,抗原性由结合的短肽所决定。热休克蛋白将结合的短肽呈递给I类MHC分子,进而激活特异性CTL和记忆性T细胞,引发机体细胞免疫反应。据最新发现gp96还可能有与MHC一样的功能,可直接将结合的多肽抗原呈递给T细胞。近年来对哺乳动物的二种主要热休克蛋白gp96和HSP70的免疫机制和作为治疗性疫苗的优越性进行了详细研究,这为乙型肝炎和乙肝继发性肝癌的免疫治疗提供了新思路。     

Evidence for Interference by Immune Complexes in the Serodiagnosis of Cryptococcosis

The latex agglutination test was used to compare cryptococcal antigen titers before and after protease treatment in 19 patients with pulmonary cryptococcosis. Antigen was detected by the LA test in 13 of 33 serum samples before protease treatment, and in an additional 13 samples following treatment. Of 26 antigen-positive serum samples, 22 (84.6%) showed an increased antigen titer after protease treatment. Using the cell slide agglutination test, antibody was detected in 3 of 19 cases. In one of these 3, antigen could only be detected after protease treatment. Soluble immune complex was prepared in vitro using anti-C. neoformans rabbit antiserum and polysaccharide antigen of C. neoformans, and the effects of immune complexes on the LA test were examined. In this experimental model, soluble immune complexes seemed to be observed in antibody excess region, because the antigen titers were increased after the protease treatment. We concluded that C. neoformans capsular polysaccharide antigen and anti-C. neoformans antibody formed soluble immune complexes in patients' sera, which interfered with antigen detection by the latex agglutination test without protease treatment.