User-Interface Coding for the CERN/GEANT Nuclear Physics Program

Explanations will be given of the various user-written routines required by the Monte Carlo detector-modeling program GEANT, developed by CERN, the European Organization for Nuclear Research. User-written routines must be linked with the CERN library to accomplish the researcher\u27s intentions. Examples will illustrate how GEANT passes information to subprograms needed to model events. Various data structures used by GEANT library calls and included in each user routine, are similarly illustrated. Both computational-speed and memory-size limitations need to be factored into the construction of a simulation model. This will constrain the calls used in the user-written routines. Examples are provided of GEANT input data flags, defined by the user to determine simulation parameters and to control various testing choices in GEANT

Dynamical structure of the inner 100 AU of the deeply embedded protostar IRAS 16293-2422

A fundamental question about the early evolution of low-mass protostars is when circumstellar disks may form. High angular resolution observations of molecular transitions in the (sub)millimeter wavelength windows make it possible to investigate the kinematics of the gas around newly-formed stars, for example to identify the presence of rotation and infall. IRAS 16293-2422 was observed with the extended Submillimeter Array (eSMA) resulting in subarcsecond resolution (0.46" x 0.29", i.e. $\sim$ 55 $\times$ 35~AU) images of compact emission from the C$^{17}$O (3-2) and C$^{34}$S (7-6) transitions at 337~GHz (0.89~mm). To recover the more extended emission we have combined the eSMA data with SMA observations of the same molecules. The emission of C$^{17}$O (3-2) and C$^{34}$S (7-6) both show a velocity gradient oriented along a northeast-southwest direction with respect to the continuum marking the location of one of the components of the binary, IRAS16293A. Our combined eSMA and SMA observations show that the velocity field on the 50--400~AU scales is consistent with a rotating structure. It cannot be explained by simple Keplerian rotation around a single point mass but rather needs to take into account the enclosed envelope mass at the radii where the observed lines are excited. We suggest that IRAS 16293-2422 could be among the best candidates to observe a pseudo-disk with future high angular resolution observations.Comment: Accepted for publication in ApJ, 18 pages, 10 figure

Experimental Bovine Spongiform Encephalopathy in Squirrel Monkeys:The Same Complex Proteinopathy Appearing after Very Different Incubation Times

Incubation periods in humans infected with transmissible spongiform encephalopathy (TSE) agents can exceed 50 years. In humans infected with bovine spongiform encephalopathy (BSE) agents, the effects of a “species barrier,” often observed when TSE infections are transmitted from one species to another, would be expected to increase incubation periods compared with transmissions of same infectious agents within the same species. As part of a long-term study investigating the susceptibility to BSE of cell cultures used to produce vaccines, we inoculated squirrel monkeys (Saimiri sp., here designated SQ) with serial dilutions of a bovine brain suspension containing the BSE agent and monitored them for as long as ten years. Previously, we showed that SQ infected with the original “classical” BSE agent (SQ-BSE) developed a neurological disease resembling that seen in humans with variant CJD (vCJD). Here, we report the final characterization of the SQ-BSE model. We observed an unexpectedly marked difference in incubation times between two animals inoculated with the same dilution and volume of the same C-BSE bovine brain extract on the same day. SQ-BSE developed, in addition to spongiform changes and astrogliosis typical of TSEs, a complex proteinopathy with severe accumulations of protease-resistant prion protein (PrP(TSE)), hyperphosphorylated tau (p-tau), ubiquitin, and α-synuclein, but without any amyloid plaques or β-amyloid protein (Aβ) typical of Alzheimer’s disease. These results suggest that PrP(TSE) enhanced the accumulation of several key proteins characteristically seen in human neurodegenerative diseases. The marked variation in incubation periods in the same experimental TSE should be taken into account when modeling the epidemiology of human TSEs

Predicting potential global and future distributions of the African armyworm (Spodoptera exempta) using Species Distribution Models

Invasive species have historically been a problem derived from global trade and transport. To aid in the control and management of these species, Species Distribution Models (SDMs) have been used to help predict possible areas of expansion. Our focal organism, the African Armyworm (AAW), has historically been known as an important pest species in Africa, occurring at high larval densities and causing outbreaks that can cause enormous economic damage to staple crops. The goal of this study is to map the AAW’s present and potential distribution in three future scenarios for the region, and the potential global distribution if the species were to invade other territories, using 40 years of data on more than 700 larval outbreak reports from Kenya and Tanzania. The present distribution in East Africa coincides with its previously known distribution, as well as other areas of grassland and cropland, which are the host plants for this species. The different future climatic scenarios show broadly similar potential distributions in East Africa to the present day. The predicted global distribution shows areas where the AAW has already been reported, but also shows many potential areas in the Americas where, if transported, environmental conditions are suitable for AAW to thrive and where it could become an invasive species

Curcuphenol possesses an unusual histone deacetylase enhancing activity that counters immune escape in metastatic tumours

Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity

Hippocampal Sclerosis of Aging, a Prevalent and High-Morbidity Brain Disease

Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5-30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available

Le Forum, Vol. 41 No. 1

https://digitalcommons.library.umaine.edu/francoamericain_forum/1090/thumbnail.jp

\u3cem\u3eABCC9\u3c/em\u3e Gene Polymorphism Is Associated with Hippocampal Sclerosis of Aging Pathology

Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer\u27s Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer\u27s Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer\u27s Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically confirmed, provided statistical power to test for risk alleles with large effect size. A two-tier study design included GWAS from cohorts #1-3 (Stage I) to identify promising SNP candidates, followed by focused evaluation of particular SNPs in cohorts #4-5 (Stage II). Polymorphism in the ATP-binding cassette, sub-family C member 9 (ABCC9) gene, also known as sulfonylurea receptor 2, was associated with HS-Aging pathology. In the meta-analyzed Stage I GWAS, ABCC9 polymorphisms yielded the lowest p values, and factoring in the Stage II results, the meta-analyzed risk SNP (rs704178:G) attained genome-wide statistical significance (p = 1.4 × 10-9), with odds ratio (OR) of 2.13 (recessive mode of inheritance). For SNPs previously linked to hippocampal sclerosis, meta-analyses of Stage I results show OR = 1.16 for rs5848 (GRN) and OR = 1.22 rs1990622 (TMEM106B), with the risk alleles as previously described. Sulfonylureas, a widely prescribed drug class used to treat diabetes, also modify human ABCC9 protein function. A subsample of patients from the NACC database (n = 624) were identified who were older than age 85 at death with known drug history. Controlling for important confounders such as diabetes itself, exposure to a sulfonylurea drug was associated with risk for HS-Aging pathology (p = 0.03). Thus, we describe a novel and targetable dementia risk factor