Machine learning in electronic-quantum-matter imaging experiments.

For centuries, the scientific discovery process has been based on systematic human observation and analysis of natural phenomena1. Today, however, automated instrumentation and large-scale data acquisition are generating datasets of such large volume and complexity as to defy conventional scientific methodology. Radically different scientific approaches are needed, and machine learning (ML) shows great promise for research fields such as materials science2-5. Given the success of ML in the analysis of synthetic data representing electronic quantum matter (EQM)6-16, the next challenge is to apply this approach to experimental data-for example, to the arrays of complex electronic-structure images17 obtained from atomic-scale visualization of EQM. Here we report the development and training of a suite of artificial neural networks (ANNs) designed to recognize different types of order hidden in such EQM image arrays. These ANNs are used to analyse an archive of experimentally derived EQM image arrays from carrier-doped copper oxide Mott insulators. In these noisy and complex data, the ANNs discover the existence of a lattice-commensurate, four-unit-cell periodic, translational-symmetry-breaking EQM state. Further, the ANNs determine that this state is unidirectional, revealing a coincident nematic EQM state. Strong-coupling theories of electronic liquid crystals18,19 are consistent with these observations.

Atomic-scale electronic structure of the cuprate pair density wave state coexisting with superconductivity.

The defining characteristic of hole-doped cuprates is d-wave high temperature superconductivity. However, intense theoretical interest is now focused on whether a pair density wave state (PDW) could coexist with cuprate superconductivity [D. F. Agterberg et al., Annu. Rev. Condens. Matter Phys. 11, 231 (2020)]. Here, we use a strong-coupling mean-field theory of cuprates, to model the atomic-scale electronic structure of an eight-unit-cell periodic, d-symmetry form factor, pair density wave (PDW) state coexisting with d-wave superconductivity (DSC). From this PDW + DSC model, the atomically resolved density of Bogoliubov quasiparticle states [Formula: see text] is predicted at the terminal BiO surface of Bi2Sr2CaCu2O8 and compared with high-precision electronic visualization experiments using spectroscopic imaging scanning tunneling microscopy (STM). The PDW + DSC model predictions include the intraunit-cell structure and periodic modulations of [Formula: see text], the modulations of the coherence peak energy [Formula: see text] and the characteristics of Bogoliubov quasiparticle interference in scattering-wavevector space [Formula: see text] Consistency between all these predictions and the corresponding experiments indicates that lightly hole-doped Bi2Sr2CaCu2O8 does contain a PDW + DSC state. Moreover, in the model the PDW + DSC state becomes unstable to a pure DSC state at a critical hole density p*, with empirically equivalent phenomena occurring in the experiments. All these results are consistent with a picture in which the cuprate translational symmetry-breaking state is a PDW, the observed charge modulations are its consequence, the antinodal pseudogap is that of the PDW state, and the cuprate critical point at p* ≈ 19% occurs due to disappearance of this PDW.

Detection of a Cooper-pair density wave in Bi2Sr2CaCu2O8+x.

The quantum condensate of Cooper pairs forming a superconductor was originally conceived as being translationally invariant. In theory, however, pairs can exist with finite momentum Q, thus generating a state with a spatially modulated Cooper-pair density. Such a state has been created in ultracold (6)Li gas but never observed directly in any superconductor. It is now widely hypothesized that the pseudogap phase of the copper oxide superconductors contains such a 'pair density wave' state. Here we report the use of nanometre-resolution scanned Josephson tunnelling microscopy to image Cooper pair tunnelling from a d-wave superconducting microscope tip to the condensate of the superconductor Bi2Sr2CaCu2O8+x. We demonstrate condensate visualization capabilities directly by using the Cooper-pair density variations surrounding zinc impurity atoms and at the Bi2Sr2CaCu2O8+x crystal supermodulation. Then, by using Fourier analysis of scanned Josephson tunnelling images, we discover the direct signature of a Cooper-pair density modulation at wavevectors QP ≈ (0.25, 0)2π/a0 and (0, 0.25)2π/a0 in Bi2Sr2CaCu2O8+x. The amplitude of these modulations is about five per cent of the background condensate density and their form factor exhibits primarily s or s' symmetry. This phenomenology is consistent with Ginzburg-Landau theory when a charge density wave with d-symmetry form factor and wavevector QC = QP coexists with a d-symmetry superconductor; it is also predicted by several contemporary microscopic theories for the pseudogap phase.

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition.

LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies.

Magnetic field-induced pair density wave state in the cuprate vortex halo.

High magnetic fields suppress cuprate superconductivity to reveal an unusual density wave (DW) state coexisting with unexplained quantum oscillations. Although routinely labeled a charge density wave (CDW), this DW state could actually be an electron-pair density wave (PDW). To search for evidence of a field-induced PDW, we visualized modulations in the density of electronic states N(r) within the halo surrounding Bi2Sr2CaCu2O8 vortex cores. We detected numerous phenomena predicted for a field-induced PDW, including two sets of particle-hole symmetric N(r) modulations with wave vectors QP and 2Q P , with the latter decaying twice as rapidly from the core as the former. These data imply that the primary field-induced state in underdoped superconducting cuprates is a PDW, with approximately eight CuO2 unit-cell periodicity and coexisting with its secondary CDWs.

AutoCSA, an algorithm for high throughput DNA sequence variant detection in cancer genomes.

UNLABELLED: The undertaking of large-scale DNA sequencing screens for somatic variants in human cancers requires accurate and rapid processing of traces for variants. Due to their often aneuploid nature and admixed normal tissue, heterozygous variants found in primary cancers are often subtle and difficult to detect. To address these issues, we have developed a mutation detection algorithm, AutoCSA, specifically optimized for the high throughput screening of cancer samples. AVAILABILITY: http://www.sanger.ac.uk/genetics/CGP/Software/AutoCSA.

Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.

We describe three families with X-linked mental retardation, two with a deletion of a single amino acid and one with a missense mutation in the proximal domain of the RSK2(RPS6KA3) (ribosomal protein S6 kinase, 90 kDa, polypeptide 3) protein similar to mutations found in Coffin-Lowry syndrome (CLS). In two families, the clinical diagnosis had been nonsyndromic X-linked mental retardation. In the third family, although CLS had been suspected, the clinical features were atypical and the degree of intellectual disability much less than expected. These families show that strict reliance on classical clinical criteria for mutation testing may result in a missed diagnosis. A less targeted screening approach to mutation testing is advocated.

Duodenal bile acids in infancy.

Duodenal bile acids have been estimated in three age groups in infancy from birth to 7 months, and age-related changes have been shown. The lowest concentrations of duodenal bile acids occurred in the youngest infants, and increasing concentrations were found with increasing age. Taurine conjugated bile acids predominated in early infancy, while in older infants bile acids were mainly conjugated with glycine. The probable presence of taurolithocholic acid in the duodenal bil of 2 newborns before the establishment of a gastrointestinal microflora remains to be confirmed, but could result either from transplacental passage of secondary bile acids or from endogenous synthesis by the fetal liver.

Control of hyperlipidaemia in juvenile diabetes. Standard and corn-oil diets compared over a period of 10 years.

The results of the first 10 years of a prospective study of the effect of corn-oil and standard diets given to diabetic children since diagnosis suggest that the corn-oil diets currently available in Britain are not acceptable to most diabetic children and adolescents. Attempts to administer such diets may result in hyperpre-beta-lipoproteinaemia. In most diabetic children normal serum lipid levels can be maintained with adequate diabetic control and a standard diabetic diet.

Duodenal bile acids in infants with protracted diarrhoea.

Bile acids were estimated in the duodenum of infants with protracted diarrhoea and compared with those in a control group. Significantly lower levels of total bile acids were found in infants with protracted diarrhoea, a finding which may be due to ileal dysfunction. Low concentrations of total bile acids may contribute to the poor nutritional state of these patients by impairing the normal digestion and absorption of dietary fat and fat-soluble vitamins. The absence of deconjugated bile acids in the duodenal juice of most infants with protracted diarrhoea suggests that they do not contribute significantly to the pathophysiology of this disorder.

The gene for cherubism maps to chromosome 4p16.3.

Cherubism is a rare familial disease of childhood characterized by proliferative lesions within the mandible and maxilla that lead to prominence of the lower face and an appearance reminiscent of the cherubs portrayed in Renaissance art. Resolution of these bony abnormalities is often observed after puberty. Many cases are inherited in an autosomal dominant fashion, although several cases without a family history have been reported. Using two families with clinically, radiologically, and/or histologically proved cherubism, we have performed a genomewide linkage search and have localized the gene to chromosome 4p16.3, with a maximum multipoint LOD score of 5. 64. Both families showed evidence of linkage to this locus. Critical meiotic recombinants place the gene in a 3-cM interval between D4S127 and 4p-telomere. Within this region a strong candidate is the gene for fibroblast growth factor receptor 3 (FGFR3); mutations in this gene have been implicated in a diverse set of disorders of bone development.

A gene for lymphedema-distichiasis maps to 16q24.3.

Lymphedema-distichiasis (LD) is a dominantly inherited syndrome with onset of lymphedema at or just after puberty. Most affected individuals have distichiasis-fine hairs arising inappropriately from the eyelid meibomian glands-which is evident from birth. A study of three families with LD has shown linkage to chromosome 16q24.3, and subsequent analysis of the region for recombinant genes places the locus between D16S422 and D16S3074, a distance of approximately 16 cM. Possible candidate genes in this interval include the N-proteinase for type 3 collagen, PCOLN3; the metalloprotease PRSM1; and the cell matrix-adhesion regulator, CMAR.