939 research outputs found
Comment on Higgs Inflation and Naturalness
We rebut the recent claim (arXiv:0912.5463) that Einstein-frame scattering in
the Higgs inflation model is unitary above the cut-off energy Lambda ~ Mp/xi.
We show explicitly how unitarity problems arise in both the Einstein and Jordan
frames of the theory. In a covariant gauge they arise from non-minimal Higgs
self-couplings, which cannot be removed by field redefinitions because the
target space is not flat. In unitary gauge, where there is only a single scalar
which can be redefined to achieve canonical kinetic terms, the unitarity
problems arise through non-minimal Higgs-gauge couplings.Comment: 5 pages, 1 figure V3: Journal Versio
EPS mid-career prize 2018: Inference within episodic memory reflects pattern completion
Recollection of episodic memories is a process of reconstruction where coherent events are inferred from subsets of remembered associations. Here, we investigated the formation of multielement events from sequential presentation of overlapping pairs of elements (people, places, and objects/animals), interleaved with pairs from other events. Retrievals of paired associations from a fully observed event (e.g., AB, BC, AC) were statistically dependent, indicating a process of pattern completion, but retrievals from a partially observed event (e.g., AB, BC, CD) were not. However, inference for unseen "indirect" associations (i.e., AC, BD or AD) from a partially observed event showed strong dependency with each other and with linking direct associations from that event. In addition, inference of indirect associations correlated with the product of performance on the linking direct associations across events (e.g., AC with ABxBC) but not on the non-linking association (e.g., AC with CD). These results were seen across three experiments, with greater differences in dependency between indirect and direct associations when they were separately tested, but similar results following single and repeated presentations of the direct associations. The results could be accounted for by a simple auto-associative network model of hippocampal memory function. Our findings suggest that pattern completion supports recollection of fully observed multielement events and the inference of indirect associations in partly observed multielement events, mediated via the directly observed linking associations (although the direct associations themselves were retrieved independently). Together with previous work, our results suggest that associative inference plays a key role in reconstructive episodic memory and does so through hippocampal pattern completion
On Inflation with Non-minimal Coupling
A simple realization of inflation consists of adding the following operators
to the Einstein-Hilbert action: (partial phi)^2, lambda phi^4, and xi phi^2 R,
with xi a large non-minimal coupling. Recently there has been much discussion
as to whether such theories make sense quantum mechanically and if the inflaton
phi can also be the Standard Model Higgs. In this note we answer these
questions. Firstly, for a single scalar phi, we show that the quantum field
theory is well behaved in the pure gravity and kinetic sectors, since the
quantum generated corrections are small. However, the theory likely breaks down
at ~ m_pl / xi due to scattering provided by the self-interacting potential
lambda phi^4. Secondly, we show that the theory changes for multiple scalars
phi with non-minimal coupling xi phi dot phi R, since this introduces
qualitatively new interactions which manifestly generate large quantum
corrections even in the gravity and kinetic sectors, spoiling the theory for
energies > m_pl / xi. Since the Higgs doublet of the Standard Model includes
the Higgs boson and 3 Goldstone bosons, it falls into the latter category and
therefore its validity is manifestly spoiled. We show that these conclusions
hold in both the Jordan and Einstein frames and describe an intuitive analogy
in the form of the pion Lagrangian. We also examine the recent claim that
curvature-squared inflation models fail quantum mechanically. Our work appears
to go beyond the recent discussions.Comment: 14 pages, 2 figures. Version 2: Clarified findings and improved
wording. Elaborated important sections and removed an unnecessary section.
Added references. Version 3: Updated towards JHEP version. Version 4: Final
JHEP versio
Location-dependent threat and associated neural abnormalities in clinical anxiety
Anxiety disorders are characterized by maladaptive defensive responses to distal or uncertain threats. Elucidating neural mechanisms of anxiety is essential to understand the development and maintenance of anxiety disorders. In fMRI, patients with pathological anxiety (ANX, n = 23) and healthy controls (HC, n = 28) completed a contextual threat learning paradigm in which they picked flowers in a virtual environment comprising a danger zone in which flowers were paired with shock and a safe zone (no shock). ANX compared with HC showed 1) decreased ventromedial prefrontal cortex and anterior hippocampus activation during the task, particularly in the safe zone, 2) increased insula and dorsomedial prefrontal cortex activation during the task, particularly in the danger zone, and 3) increased amygdala and midbrain/periaqueductal gray activation in the danger zone prior to potential shock delivery. Findings suggest that ANX engage brain areas differently to modulate context-appropriate emotional responses when learning to discriminate cues within an environment
Inflation with Non-minimal Gravitational Couplings and Supergravity
We explore in the supergravity context the possibility that a Higgs scalar
may drive inflation via a non-minimal coupling to gravity characterised by a
large dimensionless coupling constant. We find that this scenario is not
compatible with the MSSM, but that adding a singlet field (NMSSM, or a variant
thereof) can very naturally give rise to slow-roll inflation. The inflaton is
necessarily contained in the doublet Higgs sector and occurs in the D-flat
direction of the two Higgs doublets.Comment: 13 pages, 1 figur
Solution NMR assignment of the C-terminal domain of human chTOG
The microtubule regulatory protein colonic and hepatic tumor overexpressed gene (chTOG), also known as cytoskeleleton associated protein 5 (CKAP5) plays an important role in organizing the cytoskeleton and in particular in the assembly of k-fibres in mitosis. Recently, we dissected the hitherto poorly understood C-terminus of this protein by discovering two new domains—a cryptic TOG domain (TOG6) and a smaller, helical domain at the very C-terminus. It was shown that the C-terminal domain is important for the interaction with the TACC domain in TACC3 during the assembly of k-fibres in a ternary complex that also includes clathrin. Here we now present the solution NMR assignment of the chTOG C-terminal domain which confirms our earlier prediction that it is mainly made of α-helices. However, the appearance of the 1H–15N HSQC spectrum is indicative of the presence of a considerable amount of unstructured and possibly flexible portions of protein in the domain
Monoclonal antibody levels and protection from COVID-19
Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies (mAb) in preventing symptomatic SARS-CoV-2 infection. We use data on the in vivo concentration of mAb and the associated protection from COVID-19 over time to model the dose-response relationship of mAb for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a mAb concentration of 96-fold of the in vitro IC50 (95% CI: 32—285). This relationship provides a tool for predicting the prophylactic efficacy of new mAb and against SARS-CoV-2 variants. Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either mAb treatment or vaccination. We find no significant difference between the 50% protective titer for mAb and vaccination, although sample sizes limited the power to detect a difference
Effects of a Single Intra-Articular Injection of a Microsphere-Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study
Background: Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs.
Methods: In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit.
Results: The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: −3.12 versus −2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments.
Conclusions: FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point)
Immigrant community integration in world cities
As a consequence of the accelerated globalization process, today major cities
all over the world are characterized by an increasing multiculturalism. The
integration of immigrant communities may be affected by social polarization and
spatial segregation. How are these dynamics evolving over time? To what extent
the different policies launched to tackle these problems are working? These are
critical questions traditionally addressed by studies based on surveys and
census data. Such sources are safe to avoid spurious biases, but the data
collection becomes an intensive and rather expensive work. Here, we conduct a
comprehensive study on immigrant integration in 53 world cities by introducing
an innovative approach: an analysis of the spatio-temporal communication
patterns of immigrant and local communities based on language detection in
Twitter and on novel metrics of spatial integration. We quantify the "Power of
Integration" of cities --their capacity to spatially integrate diverse
cultures-- and characterize the relations between different cultures when
acting as hosts or immigrants.Comment: 13 pages, 5 figures + Appendi
MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo
Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice.
Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV.
Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls.
Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD
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