Project description:Model with functions depending on Age, Male, BP (Blood Pressure).
There are 3 disease states: Healthy, Sick, and Dead, where the Dead state is terminal. The yearly transition probabilities are: Healthy to Dead: Age/1000; Healthy to Sick: According to function F1 depending on Age and Male and BP; Sick to Healthy: 0.1; Sick to Dead: according to function F2 depending on Age and Male.
Pre-Transition Rules: Age increased by 1 and BP by Age/10 each simulation cycle. Post-Transition Rules: Treatment = BP>140 , becomes 1 when BP crosses 140 threshold; BP =BP-Treatment*10 , meaning a drop of 10 once treatment is applied; CostThisYear = Age + \Treatment*10 , cost depends on age and if treatment was taken; Cost= Cost + CostThisYear , it accumulates cost over time.
Initial conditions: Healthy = (50 Male, 50 Female with Age =1,2,...,50 for each individual), BP =120, Sick = (0,0) and Dead = (0,0).
Output: Number of men and women in each disease state for years 1-10 and their ages and costs in each state. A stratified report by male and female and young – up to age 30 and old above age 30 is produced.
Project description:The extensive peat bogs of Southern Scandinavia have yielded rich Mesolithic archaeological assemblages, which has informed prehistoric studies for more than a century. Central to this has been the first recognizably Mesolithic culture, the Maglemose (c. 11,000 - 8,000 BP), first described in 1903 which has become a yardstick against which all other Early Mesolithic cultures have been compared. Despite the excellent preservation of organic material, we have for the first time conducted a combined investigation of the typology, species composition and absolute chronology of Maglemose bone points. A demonstrable and significant change in barb morphology can be directly linked to a significant paucity of finds in Southern Scandinavia around 10,300 cal BP, potentially linked to climate change. Peptide mass fingerprinting (ZooMS) reveals that the majority of bone points are made from cervids and bovines. The ribs of bovines; for instance, are more frequently utilized following the hiatus. Furthermore, the marked change in barbed bone point morphology coincides with a change in lithic technology. This change in material culture has been shown to arrive archaeologically with eastern pioneers and colonisations through Fennoscandinavia. We, therefore, propose that the Maglemose culture in Southern Scandinavia is fundamentally divided into an Early Complex (c. 11,600 - 10,300 cal BP) and a Late Complex (c. 10,300 - 8,600 cal BP): the former characterized by percussion blade production and “fine-barbed bone points” and the latter characterized by the innovations of pressure-blade production and “larger barbed bone points”. Finally, through these integrated analyses we are able to show that a single artifact type can be used as a proxy for human populations as well as inferences on potential climate changes.
Project description:Proteomic sex estimation of human remains via liquid chromatography tandem mass spectrometry (LC- MS/MS) of sexually dimorphic amelogenin peptides in tooth enamel. The human remains analyzed in this study were recovered from two archaeological sites, Síi Túupentak (CA-ALA-565; ca. 200-600 cal BP) and Rummey Ta Kuččuwiš Tiprectak (CA-ALA-704/H; ca. 180-2240 cal. BP), Late Holocene ancestral Ohlone villages in Central California. The X and Y chromosomes code for distinctive isoforms of amelogenin proteins, AMELX_HUMAN and AMELY_HUMAN. Fragments of these proteins can be detected using shotgun liquid chromatography mass spectrometry and assigned to the AMELX or AMELY isoform. We use nano-liquid chromatography coupled with orbitrap tandem mass spectrometry (LC-orbitrap-MS/MS). Signals of all peptides that can be unambiguously attributed to either AMELY or AMELX isoforms are summed and normalized for sample weight. Confident detection of AMELY specific peptides provides an unambiguous indicator of a male sex chromosome.
Project description:Human skeletal tissue contains an abundance of proteins some of which may be preserved over geological timescales. The profiling of proteins from ancient individuals — or palaeoproteomics —has begun to provide new information about the diseases suffered in past societies. We describe here the first dental palaeoproteomic profiles of Iron Age individuals, collected from the site of Long Long Rak rockshelter in northwest Thailand. We recovered amino acid sequences for thousands of proteins preserved in their dental tissue, however, it is evident that these palaeoproteomic profiles comprise a palimpsest of modifications that occurred both ante-mortem and post-mortem. Palaeoproteomic profiles are able to categorise disease and show the capacity of these individuals for harboring a variety of illnesses prior to death. Here we apply for the first time palaeoproteomic analysis to five prehistoric human teeth from Southeast Asia. We combine this method with stable isotope analysis using δ18O and δ13C values to broadly identify the diet of these individuals. The specimens were collected from log coffins contained within the Iron Age site of Long Long Rak (LLR) rockshelter in Pang Mapha district, Mae Hong Son Province, northwest Thailand.. Radiocarbon dating shows these log coffins to date within the range of 1,960±30 cal. yr BP to 1,636±44 cal. yr BP.
Project description:The transcription factors LEAFY (LFY) and APETALA1 (AP1), together with the AP1 paralog CAULIFLOWER (CAL), control the onset of flower development in a partially redundant manner. This redundancy is thought to be mediated, at least in part, through the regulation of a shared set of target genes. However, whether these genes are independently or cooperatively regulated by LFY and AP1/CAL, is currently unknown. To better understand the regulatory relationship between LFY and AP1/CAL during floral initiation, we monitored the activity of LFY in the absence of AP1/CAL function. We found that the regulation of several known LFY target genes is unaffected by AP1/CAL perturbation, while others appear to require AP1/CAL activity. Furthermore, we obtained evidence that LFY and AP1/CAL control the expression of some genes in an antagonistic manner. Notably, these include key regulators of floral initiation such TERMINAL FLOWER1 (TFL1), which had been previously reported to be directly repressed by both LFY and AP1. We show here that TFL1 expression is suppressed by AP1 but promoted by LFY. We further demonstrate that LFY has an inhibitory effect on flower formation in the absence of AP1/CAL activity. We propose that LFY and AP1/CAL may act as part of an incoherent feed-forward loop to control the establishment of a stable developmental program for the formation of flowers.
Project description:Custom microarrays were used to examine differential gene expression between pyrethroid resistant vs pyrethroid susceptible phenotypes of the dengue vector mosquito Aedes aegypti. Pyrethroid resistant population were from Cayenne (French Guiana, GUY), Baie Mahault (Guadeloupe, GUA) and Noumea (New Caledonia, CAL) whilst New Orleans lab colony represented the lab susceptible strain Pools of total RNA was extracted from the whole bodies of 3 day old female mosquitoes that had survived exposure to 0.06% deltamethrin (for GUY, GUA, CAL) . Single colour hybridization experiments were performed using labelled cDNA on the Agilent 'Aedes aegypti detox chip plus': A-MTAB-574. Four unique biological replicates per population were used in the study
Project description:Aim: Inflammation and fibrosis have been shown to be critical factors in heart failure (HF) progression. Calycosin (Cal) is the major active component of Radix astragali and has been widely used to treat inflammation in clinical practice. However, whether Cal could ameliorate myocardial infarction (MI)-induced inflammation and fibrosis and precise mechanisms remain uncertain. The aim of this study is to explore the role of Cal in HF and to clarify the underlying mechanisms. Methods: For in vivo experiments, rats underwent left anterior descending (LAD) artery ligation for HF model, and the cardioprotective effects of Cal were measured by echocardiographic assessment and histological examination. RNA-seq approach was applied to explore potential differential genes and pathways. For further mechanistic study, pro-inflammatory conditioned media (CM)-induced H9C2 cells injury model and TGFβ-stimulated cardiac fibroblasts model were applied to determine the regulatory mechanisms of Cal. Results: In vivo experiment, echocardiography results showed that Cal significantly improved heart function. GO and Reactome enrichment revealed that inflammation and fibrosis pathway are involved in Cal-treated group. KEGG enrichment indicated that PI3K-AKT pathway is enriched in the Cal-treated group. Further experiments proved that Cal alleviated cardiomyocyte inflammatory responses evidenced by down-regulating the expressions of phosphorylated IκB kinase α/β (p-IKKα/β), phosphorylated nuclear factor kapa B (p-NFκB) and tumor necrosis factor α (TNFα). Besides, Cal effectively attenuated cardiac fibrosis through the inhibitions of expressions and depositions of collagen I and collagen III. In vitro experiments, the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 could abrogate the anti-inflammation and anti-fibrosis therapeutic effects of Cal, demonstrating that the cardio-protective effects of Cal were mediated through upregulations of PI3K and serine/threonine kinase (AKT). Conclusion: Cal improves cardiac function against HF by inhibiting cardiomyocytes inflammation and fibroblasts fibrosis via activation of the PI3K-AKT pathway.
Project description:The transcription factors LEAFY (LFY) and APETALA1 (AP1)_together with the AP1 paralog CAULIFLOWER (CAL)_control the onRep_of flower development in a partially redundant manner. This redundancy is thought to be mediated_at least in part_through the regulation of a shared Rep_of target genes. However_whether these genes are independently or cooperatively regulated by LFY and AP1/CAL_is currently unknown. To better understand the regulatory relationship between LFY and AP1/CAL during floral initiation_we monitored the activity of LFY in the absence of AP1/CAL function. We found that the regulation of several known LFY target genes is unaffected by AP1/CAL perturbation_while others appear to require AP1/CAL activity. Furthermore_we obtained evidence that LFY and AP1/CAL control the expression of some genes in an antagonistic manner. Notably_these include key regulators of floral initiation such TERMINAL FLOWER1 (TFL1)_which had been previously reported to be directly repressed by both LFY and AP1. We show here that TFL1 expression is suppressed by AP1 but promoted by LFY. We further demonstrate that LFY has an inhibitory effect on flower formation in the absence of AP1/CAL activity. We propose that LFY and AP1/CAL may act as part of an incoherent feed-forward loop to control the establishment of a stable developmental program for the formation of flowers.
Project description:To understand how RUNX2 promoted the development of BPDCN, we transduced RUNX2-directed shRNA vectors in a BPDCN cell line, CAL-1 and performed microarray analysis of RUNX2-knocked down CAL-1 cells