Universality of the Pearcey process

Consider non-intersecting Brownian motions on the line leaving from the origin and forced to two arbitrary points. Letting the number of Brownian particles tend to infinity, and upon rescaling, there is a point of bifurcation, where the support of the density of particles goes from one interval to two intervals. In this paper, we show that at that very point of bifurcation a cusp appears, near which the Brownian paths fluctuate like the Pearcey process. This is a universality result within this class of problems. Tracy and Widom obtained such a result in the symmetric case, when the two target points are symmetric with regard to the origin. This asymmetry enabled us to improve considerably a result concerning the non-linear partial differential equations governing the transition probabilities for the Pearcey process, obtained by Adler and van Moerbeke

Siri Humphrey: Design Principles for an AI Policy Analyst

This workgroup considered whether the policy analysis function in government could be replaced by an artificial intelligence policy analyst (AIPA) that responds directly to requests for information and decision support from political and administrative leaders. We describe the current model for policy analysis, identify the design criteria for an AIPA, and consider its limitations should it be adopted. A core limitation is the essential human interaction between a decision maker and an analyst/advisor, which extends the meaning and purpose of policy analysis beyond a simple synthesis or technical analysis view (each of which is nonetheless a complex task in its own right). Rather than propose a wholesale replacement of policy analysts with AIPA, we reframe the question focussing on the use of AI by human policy analysts for augmenting their current work, what we term intelligence-amplified policy analysis (IAPA). We conclude by considering how policy analysts, schools of public affairs, and institutions of government will need to adapt to the changing nature of policy analysis in an era of increasingly capable AI

Caspase-1 Dependent IL-1β Secretion Is Critical for Host Defense in a Mouse Model of Chlamydia pneumoniae Lung Infection

Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the ‘inflammasome’, and is required to cleave pro-IL-1β to bioactive IL-1β. Here we demonstrate for the first time a critical requirement for IL-1β in response to CP infection. Caspase-1−/− mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-1−/− mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice phenocopies Caspase-1-deficient mice, and administration of recombinant IL-1β rescues CP infected Caspase-1−/− mice from mortality, indicating that IL-1β secretion is crucial for host immune defense against CP lung infection. In vitro investigation reveals that CP-induced IL-1β secretion by macrophages requires TLR2/MyD88 and NLRP3/ASC/Caspase-1 signaling. Entry into the cell by CP and new protein synthesis by CP are required for inflammasome activation. Neither ROS nor cathepsin was required for CP infection induced inflammasome activation. Interestingly, Caspase-1 activation during CP infection occurs with mitochondrial dysfunction indicating a possible mechanism involving the mitochondria for CP-induced inflammasome activation

Chlamydia pneumoniae Infection Induced Allergic Airway Sensitization Is Controlled by Regulatory T-Cells and Plasmacytoid Dendritic Cells

Chlamydia pneumoniae (CP) is associated with induction and exacerbation of asthma. CP infection can induce allergic airway sensitization in mice in a dose- and time-dependent manner. Allergen exposure 5 days after a low dose (mild-moderate), but not a high dose (severe) CP infection induces antigen sensitization in mice. Innate immune signals play a critical role in controlling CP infection induced allergic airway sensitization, however these mechanisms have not been fully elucidated. Wild-type, TLR2−/−, and TLR4−/− mice were infected intranasally (i.n.) with a low dose of CP, followed by i.n. exposure to human serum albumin (HSA) and challenged with HSA 2 weeks later. Airway inflammation, immunoglobulins, eosinophils, and goblet cells were measured. Low dose CP infection induced allergic sensitization in TLR2−/− mice, but not in TLR4−/− mice, due to differential Treg responses in these genotypes. TLR2−/− mice had reduced numbers of Tregs in the lung during CP infection while TLR4−/− mice had increased numbers. High dose CP infection resulted in an increase in Tregs and pDCs in lungs, which prevented antigen sensitization in WT mice. Depletion of Tregs or pDCs resulted in allergic airway sensitization. We conclude that Tregs and pDCs are critical determinants regulating CP infection-induced allergic sensitization. Furthermore, TLR2 and TLR4 signaling during CP infection may play a regulatory role through the modulation of Tregs

The Genome Sequence of the Leaf-Cutter Ant Atta cephalotes Reveals Insights into Its Obligate Symbiotic Lifestyle

Leaf-cutter ants are one of the most important herbivorous insects in the Neotropics, harvesting vast quantities of fresh leaf material. The ants use leaves to cultivate a fungus that serves as the colony's primary food source. This obligate ant-fungus mutualism is one of the few occurrences of farming by non-humans and likely facilitated the formation of their massive colonies. Mature leaf-cutter ant colonies contain millions of workers ranging in size from small garden tenders to large soldiers, resulting in one of the most complex polymorphic caste systems within ants. To begin uncovering the genomic underpinnings of this system, we sequenced the genome of Atta cephalotes using 454 pyrosequencing. One prediction from this ant's lifestyle is that it has undergone genetic modifications that reflect its obligate dependence on the fungus for nutrients. Analysis of this genome sequence is consistent with this hypothesis, as we find evidence for reductions in genes related to nutrient acquisition. These include extensive reductions in serine proteases (which are likely unnecessary because proteolysis is not a primary mechanism used to process nutrients obtained from the fungus), a loss of genes involved in arginine biosynthesis (suggesting that this amino acid is obtained from the fungus), and the absence of a hexamerin (which sequesters amino acids during larval development in other insects). Following recent reports of genome sequences from other insects that engage in symbioses with beneficial microbes, the A. cephalotes genome provides new insights into the symbiotic lifestyle of this ant and advances our understanding of host–microbe symbioses

Allergic Fungal Sinusitis: Masquerade Syndrome and Delay in Diagnosis

Allergic fungal sinusitis is a chronic inflammatory upper respiratory disorder characterized by a type I immediate hypersensitivity reaction to fungal antigens. It may present with nasal polyps, sinus obstruction, and elevated serum IgE. Histopathology may; demonstrate the presence of fungal hyphae and chronic inflammation. In its most severe forms, AFS may lead to orbital invasion, compressive optic neuropathy and intracranial extension

Ophthalmic and orbital considerations in the evaluation of skull base malignancies.

INTRODUCTION: The orbital contents, afferent and efferent visual pathways, and the cranial nerves involved in eye movement, corneal sensation and eyelid closure traverse the skull base, a region bounded by the intracranial cavity, the paranasal sinuses, and the deep spaces of the face and head. As such, tumors from above or below have potential to affect some aspect of the visual system. METHODS: We discuss here the clinical ophthalmologic and orbital considerations in the evaluation of patients with these tumors, as well as the ophthalmic sequelae of treatment with radiation or surgery (or both). And for the surgeon, we discuss the ophthalmic and orbital considerations in surgical planning, the role of the orbital surgeon in skull base surgery, and briefly discuss transorbital approaches to the skull base. RESULTS AND CONCLUSION: Ophthalmic and orbital dysfunction may be the main source of disability in patients with skull base malignancy; it is thus incumbent on those who manage patients with tumors of this region to be aware of the ophthalmic, neuro-ophthalmic and orbital manifestations, so as to best tailor therapy and monitor treatment outcomes

A case of eyelid neuroma with recurrent ptosis.

PURPOSE: We report a rare case of eyelid neuroma, discovered nine years after external levator advancement, presenting with recalcitrant ocular foreign body sensation and pain, persistent corneal epithelial defect, followed by corneal scarring, and ptosis. OBSERVATIONS: An 85-year-old man with a history of multiple skin cancers presented with left ptosis, epiphora and recalcitrant eye pain. Nine years prior to presentation, he underwent excision of melanoma in situ of the left forehead, followed by simultaneous forehead reconstruction and left external ptosis repair. At presentation, he had left ptosis and left superior corneal scarring. Eversion of the eyelid demonstrated the presence of a nodule at the superior border of the tarsus. The patient underwent simultaneous excisional biopsy of the lesion and posterior ptosis repair by Müller muscle conjunctival resection (MMCR). He experienced postoperative resolution of pain, ptosis and epiphora. Histopathologic examination demonstrated the presence of a foreign body granuloma alongside a neuroma. CONCLUSIONS: This case highlights the importance of thorough eyelid exam in individuals with ocular surface disease. We review herein the pathophysiology and histopathology of eyelid neuroma

Siri Humphrey: Design Principles for an AI Policy Analyst

This workgroup considered whether the policy analysis function in government could be replaced by an artificial intelligence policy analyst (AIPA) that responds directly to requests for information and decision support from political and administrative leaders. We describe the current model for policy analysis, identify the design criteria for an AIPA, and consider its limitations should it be adopted. A core limitation is the essential human interaction between a decision maker and an analyst/advisor, which extends the meaning and purpose of policy analysis beyond a simple synthesis or technical analysis view (each of which is nonetheless a complex task in its own right). Rather than propose a wholesale replacement of policy analysts with AIPA, we reframe the question focussing on the use of AI by human policy analysts for augmenting their current work, what we term intelligence-amplified policy analysis (IAPA). We conclude by considering how policy analysts, schools of public affairs, and institutions of government will need to adapt to the changing nature of policy analysis in an era of increasingly capable AI