Fault-tolerant one-bit addition with the smallest interesting color code.

Fault-tolerant operations based on stabilizer codes are the state of the art in suppressing error rates in quantum computations. Most such codes do not permit a straightforward implementation of non-Clifford logical operations, which are necessary to define a universal gate set. As a result, implementations of these operations must use either error-correcting codes with more complicated error correction procedures or gate teleportation and magic states, which are prepared at the logical level, increasing overhead to a degree that precludes near-term implementation. Here, we implement a small quantum algorithm, one-qubit addition, fault-tolerantly on a trapped-ion quantum computer, using the [Formula: see text] color code. By removing unnecessary error correction circuits and using low-overhead techniques for fault-tolerant preparation and measurement, we reduce the number of error-prone two-qubit gates and measurements to 36. We observe arithmetic errors with a rate of ∼1.1 × 10-3 for the fault-tolerant circuit and ∼9.5 × 10-3 for the unencoded circuit.

Evidence of scaling advantage for the quantum approximate optimization algorithm on a classically intractable problem.

The quantum approximate optimization algorithm (QAOA) is a leading candidate algorithm for solving optimization problems on quantum computers. However, the potential of QAOA to tackle classically intractable problems remains unclear. Here, we perform an extensive numerical investigation of QAOA on the low autocorrelation binary sequences (LABS) problem, which is classically intractable even for moderately sized instances. We perform noiseless simulations with up to 40 qubits and observe that the runtime of QAOA with fixed parameters scales better than branch-and-bound solvers, which are the state-of-the-art exact solvers for LABS. The combination of QAOA with quantum minimum finding gives the best empirical scaling of any algorithm for the LABS problem. We demonstrate experimental progress in executing QAOA for the LABS problem using an algorithm-specific error detection scheme on Quantinuum trapped-ion processors. Our results provide evidence for the utility of QAOA as an algorithmic component that enables quantum speedups.

Google and suicides: what can we learn about the use of internet to prevent suicides?

OBJECTIVES: This article studies the statistical relationship between the search propensity of suicide-related terms on Google and the number of suicides. STUDY DESIGN: Suicide mortality data from all American states from January 2006 to November 2014 (n = 5372) and data on Google search intensity for the same period was collected. METHODS: Regression analysis with dynamic components was performed to determine the relationship between search intensity and the number of suicides. RESULTS: First, this article finds a positive simultaneous correlation between search intensity and the number of suicides. The magnitude of this relationship has grown from 2006 to 2014 suggesting an increased reliance on the internet for suicide-related information. Second, search propensity is a significant predictor for the number of suicides for youth and for males. CONCLUSIONS: Suicide prevention websites should therefore be designed knowing that at-risk individuals in both groups are probably more prone to look for suicide-related information online.

RNA expression and disease tolerance are associated with a "keystone mutation" in the ochre sea star Pisaster ochraceus.

An overdominant mutation in an intron of the elongation factor 1-α (EF1A) gene in the sea star Pisaster ochraceus has shown itself to mediate tolerance to "sea star wasting disease", a pandemic that has significantly reduced sea star populations on the Pacific coast of North America. Here we use RNA sequencing of healthy individuals to identify differences in constitutive expression of gene regions that may help explain this tolerance phenotype. Our results show that individuals carrying this mutation have lower expression at a large contingent of gene regions. Individuals without this mutation also appear to have a greater cellular response to temperature stress, which has been implicated in the outbreak of sea star wasting disease. Given the ecological significance of P. ochraceus, these results may be useful in predicting the evolutionary and demographic future for Pacific intertidal communities.

B-Bolivia, an allele of the maize b1 gene with variable expression, contains a high copy retrotransposon-related sequence immediately upstream.

The maize (Zea mays) b1 gene encodes a transcription factor that regulates the anthocyanin pigment pathway. Of the b1 alleles with distinct tissue-specific expression, B-Peru and B-Bolivia are the only alleles that confer seed pigmentation. B-Bolivia produces variable and weaker seed expression but darker, more regular plant expression relative to B-Peru. Our experiments demonstrated that B-Bolivia is not expressed in the seed when transmitted through the male. When transmitted through the female the proportion of kernels pigmented and the intensity of pigment varied. Molecular characterization of B-Bolivia demonstrated that it shares the first 530 bp of the upstream region with B-Peru, a region sufficient for seed expression. Immediately upstream of 530 bp, B-Bolivia is completely divergent from B-Peru. These sequences share sequence similarity to retrotransposons. Transient expression assays of various promoter constructs identified a 33-bp region in B-Bolivia that can account for the reduced aleurone pigment amounts (40%) observed with B-Bolivia relative to B-Peru. Transgenic plants carrying the B-Bolivia promoter proximal region produced pigmented seeds. Similar to native B-Bolivia, some transgene loci are variably expressed in seeds. In contrast to native B-Bolivia, the transgene loci are expressed in seeds when transmitted through both the male and female. Some transgenic lines produced pigment in vegetative tissues, but the tissue-specificity was different from B-Bolivia, suggesting the introduced sequences do not contain the B-Bolivia plant-specific regulatory sequences. We hypothesize that the chromatin context of the B-Bolivia allele controls its epigenetic seed expression properties, which could be influenced by the adjacent highly repeated retrotransposon sequence.

Genetic factors required to maintain repression of a paramutagenic maize pl1 allele.

A genetic screen identified two novel gene functions required to maintain mitotically and meiotically heritable gene silencing associated with paramutation of the maize purple plant 1 (pl1) locus. Paramutation at pl1 leads to heritable alterations of pl1 gene regulation; the Pl-Rhoades (Pl-Rh) allele, which typically confers strong pigmentation to juvenile and adult plant structures, changes to a lower expression state termed Pl'-mahogany (Pl'). Paramutation spontaneously occurs at low frequencies in Pl-Rh homozygotes but always occurs when Pl-Rh is heterozygous with Pl'. We identified four mutations that caused increased Pl' pigment levels. Allelism tests revealed that three mutations identified two new maize loci, required to maintain repression 1 (rmr1) and rmr2 and that the other mutation represents a new allele of the previously described mediator of paramutation 1 (mop1) locus. RNA levels from Pl' are elevated in rmr mutants and genetic tests demonstrate that Pl' can heritably change back to Pl-Rh in rmr mutant individuals at variable frequencies. Pigment levels controlled by two pl1 alleles that do not participate in paramutation are unaffected in rmr mutants. These results suggest that RMR functions are intimately involved in maintaining the repressed expression state of paramutant Pl' alleles. Despite strong effects on Pl' repression, rmr mutant plants have no gross developmental abnormalities even after several generations of inbreeding, implying that RMR1 and RMR2 functions are not generally required for developmental homeostasis.

Identification of the residues in the Myb domain of maize C1 that specify the interaction with the bHLH cofactor R.

The maize Myb transcription factor C1 depends on the basic helix-loop-helix (bHLH) proteins R or B for regulatory function, but the closely related Myb protein P does not. We have used the similarity between the Myb domains of C1 and P to identify residues that specify the interaction between the Myb domain of C1 and the N-terminal region of R. Substitution of four predicted solvent-exposed residues in the first helix of the second Myb repeat of P with corresponding residues from C1 is sufficient to confer on P the ability to physically interact with R. However, two additional Myb domain amino acid changes are needed to make the P regulatory activity partially dependent on R in maize cells. Interestingly, when P is altered so that it interacts with R, it can activate the Bz1 promoter, normally regulated by C1 + R but not by P. Together, these findings demonstrate that the change of a few amino acids within highly similar Myb domains can mediate differential interactions with a transcriptional coregulator that plays a central role in the regulatory specificity of C1, and that Myb domains play important roles in combinatorial transcriptional regulation.

mediator of paramutation1 is required for establishment and maintenance of paramutation at multiple maize loci.

Paramutation is the directed, heritable alteration of the expression of one allele when heterozygous with another allele. Here, the isolation and characterization of a mutation affecting paramutation, mediator of paramutation1-1 (mop1-1), are described. Experiments demonstrate that the wild-type gene Mop1 is required for establishment and maintenance of the paramutant state. The mop1-1 mutation affects paramutation at the multiple loci tested but has no effect on alleles that do not participate in paramutation. The mutation does not alter the amounts of actin and ubiquitin transcripts, which suggests that the mop1 gene does not encode a global repressor. Maize plants homozygous for mop1-1 can have pleiotropic developmental defects, suggesting that mop1-1 may affect more genes than just the known paramutant ones. The mop1-1 mutation does not alter the extent of DNA methylation in rDNA and centromeric repeats. The observation that mop1 affects paramutation at multiple loci, despite major differences between these loci in their gene structure, correlations with DNA methylation, and stability of the paramutant state, suggests that a common mechanism underlies paramutation. A protein-based epigenetic model for paramutation is discussed.

Paramutation in maize.

Paramutation is a heritable change in gene expression induced by allele interactions. This review summarizes key experiments on three maize loci, which undergo paramutation. Similarities and differences between the phenomenology at the three loci are described. In spite of many differences with respect to the stability of the reduced expression states at each locus or whether paramutation correlates with DNA methylation and repeated sequences within the loci, recent experiments are consistent with a common mechanism underlying paramutation at all three loci. Most strikingly, trans-acting mutants have been isolated that prevent paramutation at all three loci and lead to the activation of silenced Mutator transposable elements. Models consistent with the hypothesis that paramutation involves heritable changes in chromatin structure are presented. Several potential roles for paramutation are discussed. These include localizing recombination to low-copy sequences within the genome, establishing and maintaining chromatin domain boundaries, and providing a mechanism for plants to transmit an environmentally influenced expression state to progeny.

Paramutation alters regulatory control of the maize pl locus.

The maize purple plant (pl) locus encodes a transcription factor required for anthocyanin pigment synthesis in vegetative and floral tissues. The strongly expressed Pl-Rhoades (Pl-Rh) allele is unstable, spontaneously changing to weaker expression states (Pl') at low frequencies and exclusively changing to Pl' in Pl'/Pl-Rh heterozygotes. The weakly expressed Pl' state is mitotically and meiotically stable, yet reversible. This type of allele-dependent, heritable alteration of gene control is called paramutation. Expression studies herein demonstrate that visible differences in anthocyanin pigment levels mirror pl RNA abundance and that pl paramutation is associated with reduced transcription of the pl gene. This transcriptional alteration is accompanied by acquisition of light-dependent regulation. Restriction endonuclease mapping indicates that these changes in pl gene regulation are not associated with detectable DNA alterations or with extensive changes in cytosine methylation patterns. Genetic tests show that Pl-Blotched (Pl-Bh), a structurally similar pl allele encoding an identical pl RNA and PL protein, does not participate in pl paramutation. This result suggests that if cis-acting sequences are required for pl paramutation they are distinct from the protein coding and immediately adjacent regions. A model is discussed in which pl paramutation results in heritable changes of chromatin structure that fundamentally alter regulatory interactions occurring during plant development.

Lack of significant changes on magnetic resonance scans before and after 2 weeks of daily left prefrontal repetitive transcranial magnetic stimulation for depression.

Repetitive transcranial magnetic stimulation (rTMS) is a new technology for exploring brain function. With this method, a small electromagnet is placed on the scalp; by activating and deactivating it, nerve cells in the underlying superficial cortex are depolarized. Several studies have found that prefrontal rTMS has potential efficacy in treating depression, and this technology, in addition to being a research tool, may soon play a role in psychiatric practice. Thus, establishing the safety of this technology is important and has been studied insufficiently. The authors performed T1-weighted three-dimensional volumetric magnetic resonance (MR) imaging on 22 depressed adults (15 active, 7 control) before and after they participated in a 2-week double-blinded, placebo-controlled trial of daily left prefrontal rTMS for the treatment of depression (a total of 16,000 stimuli). Seventeen patients also had paired T2-weighted scans. In a blinded manner, MR scans were qualitatively and quantitatively assessed for structural changes. No qualitative structural differences were observed before and after treatment. In addition, volumetric analysis of the prefrontal lobe showed no changes in the 2 weeks of the study. In conclusion, 10 days of daily prefrontal rTMS at these intensities and frequencies does not cause observable structural changes on MR scans in depressed adults.

Major recent and independent changes in levels and patterns of expression have occurred at the b gene, a regulatory locus in maize.

The b locus encodes a transcription factor that regulates the expression of genes that produce purple anthocyanin pigment. Different b alleles are expressed in distinct tissues, causing tissue-specific anthocyanin production. Understanding how phenotypic diversity is produced and maintained at the b locus should provide models for how other regulatory genes, including those that influence morphological traits and development, evolve. We have investigated how different levels and patterns of pigmentation have evolved by determining the phenotypic and evolutionary relationships between 18 alleles that represent the diversity of b alleles in Zea mays. Although most of these alleles have few phenotypic differences, five alleles have very distinct tissue-specific patterns of pigmentation. Superimposing the phenotypes on the molecular phylogeny reveals that the alleles with strong and distinctive patterns of expression are closely related to alleles with weak expression, implying that the distinctive patterns have arisen recently. We have identified apparent insertions in three of the five phenotypically distinct alleles, and the fourth has unique upstream restriction fragment length polymorphisms relative to closely related alleles. The insertion in B-Peru has been shown to be responsible for its unique expression and, in the other two alleles, the presence of the insertion correlates with the phenotype. These results suggest that major changes in gene expression are probably the result of large-scale changes in DNA sequence and/or structure most likely mediated by transposable elements.

A mutation in the pale aleurone color1 gene identifies a novel regulator of the maize anthocyanin pathway.

By screening for new seed color mutations, we have identified a new gene, pale aleurone color1 (pac1), which when mutated causes a reduction in anthocyanin pigmentation. The pac1 gene is not allelic to any known anthocyanin biosynthetic or regulatory gene. The pac1-ref allele is recessive, nonlethal, and only reduces pigment in kernels, not in vegetative tissues. Genetic and molecular evidence shows that the pac1-ref allele reduces pigmentation by reducing RNA levels of the biosynthetic genes in the pathway. The mutant does not reduce the RNA levels of either of the two regulatory genes, b and c1. Introduction of an anthocyanin structural gene promoter (a1) driving a reporter gene into maize aleurones shows that pac1-ref kernels have reduced expression resulting from the action of the a1 promoter. Introduction of the reporter gene with constructs that express the regulatory genes b and c1 or the phlobaphene pathway regulator p shows that this reduction in a1-driven expression occurs in both the presence and absence of these regulators. Our results imply that pac1 is required for either b/c1 or p activation of anthocyanin biosynthetic gene expression and that pac1 acts independently of these regulatory genes.

Epigenetic allelic states of a maize transcriptional regulatory locus exhibit overdominant gene action.

Using alleles of the maize purple plant locus (pl), which encodes a transcriptional regulator of anthocyanin pigment synthesis, we describe a case of single-locus heterosis, or overdominance, where the heterozygote displays a phenotype that is greater than either homozygote. The Pl-Rhoades (Pl-Rh) allele is subject to epigenetic changes in gene expression, resulting in quantitatively distinct expression states. Allelic states with low-expression levels, designated Pl'-mahogany (Pl'-mah), are dominant to the high-expression state of Pl-Rh. Pl'-mah states retain low-expression levels in subsequent generations when homozygous or heterozygous with Pl-Rh. However, Pl'-mah alleles frequently exhibit higher expression levels when heterozygous with other pl alleles; illustrating an overdominant allelic relationship. Higher expression levels are also observed when Pl'-mah is hemizygous. These results suggest that persistent allelic interactions between Pl'-mah and Pl-Rh are required to maintain the low-expression state and that other pl alleles are missing sequences required for this interaction. The Pl-Rh state can be sexually transmitted from Pl'-mah/pl heterozygotes, but not from Pl'-mah hemizygotes, suggesting that fixation of the high-expression state may involve synapsis. The existence of such allele-dependent regulatory mechanisms implicates a novel importance of allele polymorphisms in the genesis and maintenance of genetic variation.