Introduction to Categories and Categorical Logic

The aim of these notes is to provide a succinct, accessible introduction to some of the basic ideas of category theory and categorical logic. The notes are based on a lecture course given at Oxford over the past few years. They contain numerous exercises, and hopefully will prove useful for self-study by those seeking a first introduction to the subject, with fairly minimal prerequisites. The coverage is by no means comprehensive, but should provide a good basis for further study; a guide to further reading is included. The main prerequisite is a basic familiarity with the elements of discrete mathematics: sets, relations and functions. An Appendix contains a summary of what we will need, and it may be useful to review this first. In addition, some prior exposure to abstract algebra - vector spaces and linear maps, or groups and group homomorphisms - would be helpful.Comment: 96 page

Semantics of a Typed Algebraic Lambda-Calculus

Algebraic lambda-calculi have been studied in various ways, but their semantics remain mostly untouched. In this paper we propose a semantic analysis of a general simply-typed lambda-calculus endowed with a structure of vector space. We sketch the relation with two established vectorial lambda-calculi. Then we study the problems arising from the addition of a fixed point combinator and how to modify the equational theory to solve them. We sketch an algebraic vectorial PCF and its possible denotational interpretations

Step-Indexed Normalization for a Language with General Recursion

The Trellys project has produced several designs for practical dependently typed languages. These languages are broken into two fragments-a_logical_fragment where every term normalizes and which is consistent when interpreted as a logic, and a_programmatic_fragment with general recursion and other convenient but unsound features. In this paper, we present a small example language in this style. Our design allows the programmer to explicitly mention and pass information between the two fragments. We show that this feature substantially complicates the metatheory and present a new technique, combining the traditional Girard-Tait method with step-indexed logical relations, which we use to show normalization for the logical fragment.Comment: In Proceedings MSFP 2012, arXiv:1202.240

Long-term IL-33-producing epithelial progenitor cells in chronic obstructive lung disease

Chronic obstructive lung disease is characterized by persistent abnormalities in epithelial and immune cell function that are driven, at least in part, by infection. Analysis of parainfluenza virus infection in mice revealed an unexpected role for innate immune cells in IL-13–dependent chronic lung disease, but the upstream driver for the immune axis in this model and in humans with similar disease was undefined. We demonstrate here that lung levels of IL-33 are selectively increased in postviral mice with chronic obstructive lung disease and in humans with very severe chronic obstructive pulmonary disease (COPD). In the mouse model, IL-33/IL-33 receptor signaling was required for Il13 and mucin gene expression, and Il33 gene expression was localized to a virus-induced subset of airway serous cells and a constitutive subset of alveolar type 2 cells that are both linked conventionally to progenitor function. In humans with COPD, IL33 gene expression was also associated with IL13 and mucin gene expression, and IL33 induction was traceable to a subset of airway basal cells with increased capacities for pluripotency and ATP-regulated release of IL-33. Together, these findings provide a paradigm for the role of the innate immune system in chronic disease based on the influence of long-term epithelial progenitor cells programmed for excess IL-33 production

Photodisintegration of 4^4He into p+t

The two-body photodisintegration of $^4$He into a proton and a triton has been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid $^4$He target. This is the first measurement of the photodisintegration of $^4$He above 0.4 GeV. The differential cross sections for the $\gamma$$^4$He$\to pt$ reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. These results reinforce the conclusion of our previous study of the three-body breakup of $^3$He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22 postscrip figure

Q^2 Dependence of the S_{11}(1535) Photocoupling and Evidence for a P-wave resonance in eta electroproduction

New cross sections for the reaction $ep \to e'\eta p$ are reported for total center of mass energy $W$=1.5--2.3 GeV and invariant squared momentum transfer $Q^2$=0.13--3.3 GeV$^2$. This large kinematic range allows extraction of new information about response functions, photocouplings, and $\eta N$ coupling strengths of baryon resonances. A sharp structure is seen at $W\sim$ 1.7 GeV. The shape of the differential cross section is indicative of the presence of a $P$-wave resonance that persists to high $Q^2$. Improved values are derived for the photon coupling amplitude for the $S_{11}$(1535) resonance. The new data greatly expands the $Q^2$ range covered and an interpretation of all data with a consistent parameterization is provided.Comment: 31 pages, 9 figure

Phase 1 Study of a Combination AMA1 Blood Stage Malaria Vaccine in Malian Children

Apical Membrane Antigen-1 (AMA1) is one of the leading blood stage malaria vaccine candidates. AMA1-C1/Alhydrogel consists of an equal mixture of recombinant AMA1 from FVO and 3D7 clones of P. falciparum, adsorbed onto Alhydrogel. A Phase 1 study in semi-immune adults in Mali showed that the vaccine was safe and immunogenic, with higher antibody responses in those who received the 80 microg dose. The aim of this study was to assess the safety and immunogenicity of this vaccine in young children in a malaria endemic area.This was a Phase 1 dose escalating study in 36 healthy children aged 2-3 years started in March 2006 in Donéguébougou, Mali. Eighteen children in the first cohort were randomized 2 ratio 1 to receive either 20 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Two weeks later 18 children in the second cohort were randomized 2 ratio 1 to receive either 80 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Vaccinations were administered on Days 0 and 28 and participants were examined on Days 1, 2, 3, 7, and 14 after vaccination and then about every two months. Results to Day 154 are reported in this manuscript.Of 36 volunteers enrolled, 33 received both vaccinations. There were 9 adverse events related to the vaccination in subjects who received AMA1-C1 vaccine and 7 in those who received Hiberix. All were mild to moderate. No vaccine-related serious or grade 3 adverse events were observed. There was no increase in adverse events with increasing dose of vaccine or number of immunizations. In subjects who received the test vaccine, antibodies to AMA1 increased on Day 14 and peaked at Day 42, with changes from baseline significantly different from subjects who received control vaccine.AMA-C1 vaccine is well tolerated and immunogenic in children in this endemic area although the antibody response was short lived.Clinicaltrials.gov NCT00341250

Virosome-Formulated Plasmodium falciparum AMA-1 & CSP Derived Peptides as Malaria Vaccine: Randomized Phase 1b Trial in Semi-Immune Adults & Children

BACKGROUND\ud \ud This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children.\ud \ud METHODS\ud \ud The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5-9 years) living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90.\ud \ud RESULTS\ud \ud No serious or severe adverse events (AEs) related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0.014). In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal®V; RR  = 0.50 [95%-CI: 0.29-0.88], p = 0.02).\ud \ud CONCLUSION\ud \ud These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.\ud \ud TRIAL REGISTRATION\ud \ud ClinicalTrials.gov NCT00513669

On the pulmonary toxicity of oxygen. 4. The thyroid arena

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Experimental and Molecular Pathology 92 (2012): 140-154, doi:10.1016/j.yexmp.2011.11.006.Normally developed thyroid function is critical to the transition from fetal to neonatal life with the onset of independent thermoregulation, the most conspicuous of the many ways in which thyroid secretions act throughout the body. A role for thyroid secretions in growth and maturation of the lungs as part of the preparation for the onset of breathing has been recognized for some time but how this contributes to tissue and cell processes and defenses under the duress of respiratory distress has not been well examined. Extensive archival autopsy material was searched for thyroid and adrenal weights, first by gestational age, and then for changes during the first hours after birth as ratios to body weight. After a gestational age of 22 weeks the fetal thyroid and adrenal glands at autopsy in those with hyaline membrane disease are persistently half the size of those in "normal" infants dying with other disorders. When the thyroid is examined shortly after birth it reveals a post natal loss of mass per body weight of similar orders of magnitude which does not occur in the control group. A clinical sample of premature infants with (12) and without (14) hyaline membrane disease was tested for T4, TSH, TBG, and total serum protein. The results also demonstrate a special subset with lower birth weights at the same gestational age, and lower serum T4 and total serum protein. Ventilatory distress in newborn rabbits was induced by bilateral cervical vagotomy at 24 hours post natal following earlier injection of thyroxine (T4) or thyroid stimulating hormone (TSH) and comparisons were made with untreated animals and by dose. Early life thyroidectomy was performed followed by exposure to either air or 100% oxygen. A final experiment in air was vagotomy after thyroidectomy. Composite analysis of these methods indicates that thyroid factors are both operative and important in the newborn animal with ventilatory distress. This work and the archival data indicate those infants destined to develop hyaline membrane disease through respiratory distress are a distinct developmental and clinical subset with the point of departure from otherwise normal development and maturation in the second or early third trimester. This interval is known to be a period of marked variation in the overview indicators of fetal progress through gestational time. The initiating factor or circumstance which then separates this special subset from normal future development is placed by these observations firmly into the period when human fetal TSH dramatically rises 7-fold (17.5-25.5 weeks) followed by a lesser 3 to 4 fold increase in T4 which is extended into the early third trimester. The earlier part of this interval is characterized by the thyrotrophic action of chorionic gonadotropin (hCG). The possibility that abnormalities in the intrauterine environment secondary to maternal infection play a role within this time frame is indicated by the demonstration that interleukin-2 (IL-2) induces an anterior pituitary release of TSH. Since IL-2 has this property and is not an acute phase cytokine, some form of chronic infection or an immunopathic process seems more likely as a possible active factor in pathogenesis.The work in this report was performed under a grant to the University of Chicago from the John A. Hartford Foundation