Commensurate 4a04a_0 period Charge Density Modulations throughout the Bi2Sr2CaCu2O8+xBi_2Sr_2CaCu_2O_{8+x} Pseudogap Regime

Theories based upon strong real space (r-space) electron electron interactions have long predicted that unidirectional charge density modulations (CDM) with four unit cell (4$a_0$) periodicity should occur in the hole doped cuprate Mott insulator (MI). Experimentally, however, increasing the hole density p is reported to cause the conventionally defined wavevector $Q_A$ of the CDM to evolve continuously as if driven primarily by momentum space (k-space) effects. Here we introduce phase resolved electronic structure visualization for determination of the cuprate CDM wavevector. Remarkably, this new technique reveals a virtually doping independent locking of the local CDM wavevector at $|Q_0|=2\pi/4a_0$ throughout the underdoped phase diagram of the canonical cuprate $Bi_2Sr_2CaCu_2O_8$. These observations have significant fundamental consequences because they are orthogonal to a k-space (Fermi surface) based picture of the cuprate CDM but are consistent with strong coupling r-space based theories. Our findings imply that it is the latter that provide the intrinsic organizational principle for the cuprate CDM state

Evidence-Based Interventions and Strategies for the Grand Challenges Approach: The Need for Judgement

What is the value of evidence-based interventions in addressing “Grand Challenges”? Building upon the EPOS Grand Challenges work (Sakhrani et al., 2017), this paper explores whether evidence-based approaches developed for management and policy are relevant to addressing Grand Challenges. It discusses the criticisms of the Evidence-based Management approach and argues that evidence is a necessary, but not sufficient input in the decisionmaking process of addressing Grand Challenges

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., Annual Review of Condensed Matter Physics 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 N(r,E) is predicted at the terminal BiO surface of Bi$_2$Sr$_2$CaCu$_2$O$_8$ and compared with high-precision electronic visualization experiments using spectroscopic imaging STM. The PDW+DSC model predictions include the intra-unit-cell structure and periodic modulations of N(r,E), the modulations of the coherence peak energy $\Delta_p$ (r), and the characteristics of Bogoliubov quasiparticle interference in scattering-wavevector space (q-space). Consistency between all these predictions and the corresponding experiments indicates that lightly hole-doped Bi$_2$Sr$_2$CaCu$_2$O$_8$ 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

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

Explaining counterterrorism in the UK: Normal politics, securitized politics or performativity of the neoliberal state?

This paper seeks to explore the politics of counter terrorism in the UK. It argues that for a number of reasons, counter terrorism policy has been separated off from other policy areas and seen as securitised, exceptional or just different. The paper argues that such a separation from “normal” politics is problematic, both conceptually and empirically. It argues that much can be gained by considering counter terrorism policy through the lenses, concepts and debates which feature in other areas of British politics. The paper then examines two such lenses/debates – depoliticisation and neoliberalism. An argument is developed that counter terrorism policy is not, in the main, depoliticised, but rather overt, politicised and visible. This prominence, it is argued, is due to the ways in which neoliberalism has reduced many of the traditional roles of the state. Drawing on the work of Wacquant and Hall, the paper argues that in the absence of such traditional roles, counter terrorism offers the state an opportunity to perform its own “stateness”, to visibly display its sovereign power in a context of ever more (self-imposed) diminished powers

Zeb1 modulates hematopoietic stem cell fates required for suppressing acute myeloid leukemia

Zeb1, a zinc finger E-box binding homeobox epithelial-mesenchymal (EMT) transcription factor, confers properties of ‘stemness’, such as self-renewal, in cancer. Yet little is known about the function of Zeb1 in adult stem cells. Here, we used the hematopoietic system, as a well-established paradigm of stem cell biology, to evaluate Zeb1 mediated regulation of adult stem cells. We employed a conditional genetic approach using the Mx1-Cre system to specifically knockout (KO) Zeb1 in adult hematopoietic stem cells (HSCs) and their downstream progeny. Acute genetic deletion of Zeb1 led to rapid onset thymic atrophy and apoptosis driven loss of thymocytes and T cells. A profound cell-autonomous self-renewal defect and multi-lineage differentiation block was observed in Zeb1 KO HSCs. Loss of Zeb1 in HSCs activated transcriptional programs of deregulated HSC maintenance and multi-lineage differentiation genes, and of cell polarity, consisting of cytoskeleton, lipid metabolism/lipid membrane and cell adhesion related genes. Notably, Epithelial cell adhesion molecule (EpCAM) expression was prodigiously upregulated in Zeb1 KO HSCs, which correlated with enhanced cell survival, diminished mitochondrial metabolism, ribosome biogenesis, and differentiation capacity and an activated transcriptomic signature associated with acute myeloid leukemia (AML) signaling. ZEB1 expression was downregulated in AML patients and Zeb1 KO in the malignant counterparts of HSCs - leukemic stem cells (LSCs) - accelerated MLL-AF9 and Meis1a/Hoxa9-driven AML progression, implicating Zeb1 as a tumor suppressor in AML LSCs. Thus, Zeb1 acts as a transcriptional regulator in hematopoiesis, critically co-ordinating HSC self-renewal, apoptotic and multi-lineage differentiation fates required to suppress leukemic potential in AML

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability

Results from the first use of low radioactivity argon in a dark matter search

Liquid argon is a bright scintillator with potent particle identification properties, making it an attractive target for direct-detection dark matter searches. The DarkSide-50 dark matter search here reports the first WIMP search results obtained using a target of low-radioactivity argon. DarkSide-50 is a dark matter detector, using two-phase liquid argon time projection chamber, located at the Laboratori Nazionali del Gran Sasso. The underground argon is shown to contain Ar-39 at a level reduced by a factor (1.4 +- 0.2) x 10^3 relative to atmospheric argon. We report a background-free null result from (2616 +- 43) kg d of data, accumulated over 70.9 live-days. When combined with our previous search using an atmospheric argon, the 90 % C.L. upper limit on the WIMP-nucleon spin-independent cross section based on zero events found in the WIMP search regions, is 2.0 x 10^-44 cm^2 (8.6 x 10^-44 cm^2, 8.0 x 10^-43 cm^2) for a WIMP mass of 100 GeV/c^2 (1 TeV/c^2 , 10 TeV/c^2).Comment: Accepted by Phys. Rev.

Immunoglobulin G; structure and functional implications of different subclass modifications in initiation and resolution of allergy.

IgE and not IgG is usually associated with allergy. IgE lodged on mast cells in skin or gut and basophils in the blood allows for the prolonged duration of allergy through the persistent expression of high affinity IgE receptors. However, many allergic reactions are not dependent on IgE and are generated in the absence of allergen specific and even total IgE. Instead, IgG plasma cells are involved in induction of, and for much of the pathogenesis of, allergic diseases. The pattern of IgG producing plasma cells in atopic children and the tendency for direct or further class switching to IgE are the principle factors responsible for long-lasting sensitization of mast cells in allergic children. Indirect class switching from IgG producing plasma cells has been shown to be the predominant pathway for production of IgE while a Th2 microenvironment, genetic predisposition, and the concentration and nature of allergens together act on IgG plasma cells in the atopic tendency to undergo further immunoglobulin gene recombination. The seminal involvement of IgG in allergy is further indicated by the principal role of IgG4 in the natural resolution of allergy and as the favourable immunological response to immunotherapy. This paper will look at allergy through the role of different antibodies than IgE and give current knowledge of the nature and role of IgG antibodies in the start, maintenance and resolution of allergy