Two-magnon Raman scattering in insulating cuprates: Modifications of the effective Raman operator

Calculations of Raman scattering intensities in spin 1/2 square-lattice Heisenberg model, using the Fleury-Loudon-Elliott theory, have so far been unable to describe the broad line shape and asymmetry of the two magnon peak found experimentally in the cuprate materials. Even more notably, the polarization selection rules are violated with respect to the Fleury-Loudon-Elliott theory. There is comparable scattering in $B_{1g}$ and $A_{1g}$ geometries, whereas the theory would predict scattering in only $B_{1g}$ geometry. We review various suggestions for this discrepency and suggest that at least part of the problem can be addressed by modifying the effective Raman Hamiltonian, allowing for two-magnon states with arbitrary total momentum. Such an approach based on the Sawatzsky-Lorenzana theory of optical absorption assumes an important role of phonons as momentum sinks. It leaves the low energy physics of the Heisenberg model unchanged but substantially alters the Raman line-shape and selection rules, bringing the results closer to experiments.Comment: 7 pages, 6 figures, revtex. Contains some minor revisions from previous versio

The phase diagram of magnetic ladders constructed from a composite-spin model

White's density matrix renormalization group ({DMRG}) method has been applied to an $S= 1/2 + 1/2$ composite-spin model, which can also be considered as a two-leg ladder model. By appropriate choices of the coupling constants this model allows not only to study how the gap is opened around the gapless integrable models, but also to interpolate continuously between models with different spin lengths. We have found indications for the existence of several different massive phases.Comment: 30 pages, 8 Postscript figure

Stability analysis of agegraphic dark energy in Brans-Dicke cosmology

Stability analysis of agegraphic dark energy in Brans-Dicke theory is presented in this paper. We constrain the model parameters with the observational data and thus the results become broadly consistent with those expected from experiment. Stability analysis of the model without best fitting shows that universe may begin from an unstable state passing a saddle point and finally become stable in future. However, with the best fitted model, There is no saddle intermediate state. The agegraphic dark energy in the model by itself exhibits a phantom behavior. However, contribution of cold dark matter on the effective energy density modifies the state of teh universe from phantom phase to quintessence one. The statefinder diagnosis also indicates that the universe leaves an unstable state in the past, passes the LCDM state and finally approaches the sable state in future.Comment: 15 pages, 12 figure

Erratum: Author Correction: Identification of genes required for eye development by high-throughput screening of mouse knockouts.

[This corrects the article DOI: 10.1038/s42003-018-0226-0.]

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

Two Loop Scalar Self-Mass during Inflation

We work in the locally de Sitter background of an inflating universe and consider a massless, minimally coupled scalar with a quartic self-interaction. We use dimensional regularization to compute the fully renormalized scalar self-mass-squared at one and two loop order for a state which is released in Bunch-Davies vacuum at t=0. Although the field strength and coupling constant renormalizations are identical to those of lfat space, the geometry induces a non-zero mass renormalization. The finite part also shows a sort of growing mass that competes with the classical force in eventually turning off this system's super-acceleration.Comment: 31 pages, 5 figures, revtex4, revised for publication with extended list of reference

Genome-wide screening reveals the genetic basis of mammalian embryonic eye development.

BACKGROUND: Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome. RESULTS: Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation. CONCLUSIONS: Using genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease

Solution structures of all parallel-stranded monomeric and dimeric G-quadruplex scaffolds of the human c-kit2 promoter

Previous studies have demonstrated that nuclease hypersensitivity regions of several proto-oncogenic DNA promoters, situated upstream of transcription start sites, contain guanine-rich tracts that form intramolecular G-quadruplexes stabilized by stacked G•G•G•G tetrads in monovalent cation solution. The human c-kit oncogenic promoter, an important target in the treatment of gastrointestinal tumors, contains two such stretches of guanine-rich tracts, designated c-kit1 and c-kit2. Our previous nuclear magnetic resonance (NMR)-based studies reported on the novel G-quadruplex scaffold of the c-kit1 promoter in K+-containing solution, where we showed for the first time that even an isolated guanine was involved in G-tetrad formation. These NMR-based studies are now extended to the c-kit2 promoter, which adopts two distinct all-parallel-stranded conformations in slow exchange, one of which forms a monomeric G-quadruplex (form-I) in 20 mM K+-containing solution and the other a novel dimeric G-quadruplex (form-II) in 100 mM K+-containing solution. The c-kit2 promoter dimeric form-II G-quadruplex adopts an unprecedented all-parallel-stranded topology where individual c-kit2 promoter strands span a pair of three-G-tetrad-layer-containing all-parallel-stranded G-quadruplexes aligned in a 3′ to 5′-end orientation, with stacking continuity between G-quadruplexes mediated by a sandwiched A•A non-canonical pair. We propose that strand exchange during recombination events within guanine-rich segments, could potentially be mediated by a synapsis intermediate involving an intergenic parallel-stranded dimeric G-quadruplex

Mendelian gene identification through mouse embryo viability screening.

BACKGROUND: The diagnostic rate of Mendelian disorders in sequencing studies continues to increase, along with the pace of novel disease gene discovery. However, variant interpretation in novel genes not currently associated with disease is particularly challenging and strategies combining gene functional evidence with approaches that evaluate the phenotypic similarities between patients and model organisms have proven successful. A full spectrum of intolerance to loss-of-function variation has been previously described, providing evidence that gene essentiality should not be considered as a simple and fixed binary property. METHODS: Here we further dissected this spectrum by assessing the embryonic stage at which homozygous loss-of-function results in lethality in mice from the International Mouse Phenotyping Consortium, classifying the set of lethal genes into one of three windows of lethality: early, mid, or late gestation lethal. We studied the correlation between these windows of lethality and various gene features including expression across development, paralogy and constraint metrics together with human disease phenotypes. We explored a gene similarity approach for novel gene discovery and investigated unsolved cases from the 100,000 Genomes Project. RESULTS: We found that genes in the early gestation lethal category have distinct characteristics and are enriched for genes linked with recessive forms of inherited metabolic disease. We identified several genes sharing multiple features with known biallelic forms of inborn errors of the metabolism and found signs of enrichment of biallelic predicted pathogenic variants among early gestation lethal genes in patients recruited under this disease category. We highlight two novel gene candidates with phenotypic overlap between the patients and the mouse knockouts. CONCLUSIONS: Information on the developmental period at which embryonic lethality occurs in the knockout mouse may be used for novel disease gene discovery that helps to prioritise variants in unsolved rare disease cases