Classical Liberalism

Classical Liberalism is a political philosophy that has stood the test of time. Developed by the English philosopher John Locke, classical liberalism is rooted in the ideals of individual rights and social contract. It is ultimately a Christian philosophy, as it admits the inherent sinfulness of man and the sovereignty of God. The United States of America is the greatest application of this philosophy as it prioritizes the protection of individual liberties and derives its power from the consent of the governed

LARCRIM user's guide, version 1.0

LARCRIM is a relational database management system (RDBMS) which performs the conventional duties of an RDBMS with the added feature that it can store attributes which consist of arrays or matrices. This makes it particularly valuable for scientific data management. It is accessible as a stand-alone system and through an application program interface. The stand-alone system may be executed in two modes: menu or command. The menu mode prompts the user for the input required to create, update, and/or query the database. The command mode requires the direct input of LARCRIM commands. Although LARCRIM is an update of an old database family, its performance on modern computers is quite satisfactory. LARCRIM is written in FORTRAN 77 and runs under the UNIX operating system. Versions have been released for the following computers: SUN (3 & 4), Convex, IRIS, Hewlett-Packard, CRAY 2 & Y-MP

Assessing drivers of plantation forest productivity on eroded and non-eroded soils in hilly land, eastern North Island, New Zealand

Methods: The impact of soil erosion by mass movement on forest productivity was investigated in a paired plot trial in a planted forest in a mainly hilly to steepland catchment (Pakuratahi) near Napier, eastern North Island, New Zealand. Tree growth and form were measured and soil properties analysed to compare productivity and productivity drivers in adjacent non-eroded and eroded plots. Background: The effect of soil erosion on New Zealand production forestry is not well known and there has been no research prior to our study into the relationship between soil nutrient status and planted forests growing in eroded soils in steeplands. Results: Regression analysis showed that the decreased soil total nitrogen, total carbon, total phosphorus, and soil organic matter content in eroded plots had a negative impact on tree volume, resulting in a 10% decrease in measured tree volume. Based on an assessment of log quality, trees in the eroded plots were forecast to produce 16% less volume from high-quality pruned logs (with associated reduction in revenue of around $4000 per hectare), than trees in non-eroded plots. The total recoverable volume (TRV), estimated (for a 25-year rotation) from the measured Pinus radiata D. Don trees growing on the eroded sites, was valued at$68,500, about 9% less than the estimated TRV from trees measured on non-eroded plots ($76,000). Tree form and mean tree height in eroded and non-eroded plots were not significantly different. Conclusions: Soil erosion impacts production in planted forests. Afforestation of erodible land provides a valuable ecosystem service through land and soil stabilisation but this service is currently not reflected in the market prices for timber in New Zealand. Maintaining the productive capacity of erodible soils through practices such as fertilisation or continuous-cover forestry can add further costs to production forestry. To ensure that sustainable forest practices are carried out to protect the productivity of soils, financial incentives may be justified

Alternative lengthening of telomeres, ATRX loss and H3â K27M mutations in histologically defined pilocytic astrocytoma with anaplasia

Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fiftyâ seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3â 75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomereâ specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3â K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRXâ (20/24, 83%) or ALTâ /ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3â K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PAâ A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3â K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/1/bpa12646_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/2/bpa12646.pd

FFPE breast tumour blocks provide reliable sources of both germline and malignant DNA for investigation of genetic determinants of individual tumour responses to treatment

Background: Bio-banked formalin-fixed paraffin-embedded (FFPE) tissues provide an excellent opportunity for translational genomic research. Historically matched blood has not always been collected as a source of germline DNA. This project aimed to establish if normal FFPE breast tissue could be used as an alternative to blood. Methods: Exome sequencing was carried out on matched tumour tissue, normal breast tissue and blood on five patients in the START trial. Retrieved samples had been archived at different centres for at least 13 years. Following tissue macro-dissection and DNA extraction, targeted exome capture was performed using SureSelect Human All Exome v5 reagents (Agilent). Illumina paired-end libraries were prepared from the captured target regions and sequenced on a HiSeq2500 (Illumina) acquiring 2 × 75 bp reads. Somatic variants were called using the MuTect software analysis tool and copy number abnormalities (CNA) were identified using CNVkit. Targeted sequencing and droplet digital PCR were used to validate somatic variants and CNA, respectively. Results: Overlap of somatic variants and CNA called on tumour versus blood and tumour versus normal breast tissue was good. Agreement in somatic variant calling ranged from 76.9 to 93.6%. Variants with an allele frequency lower than 10% were more difficult to validate irrespective of the type of germline DNA used. Pearson’s correlation coefficients for paired comparisons of CNA using blood or normal tissue as reference ranged from 0.70 to 0.94. Conclusions: There is good correlation between the somatic mutations and CNA called using archived blood or normal breast tissue as germline reference material

Expression of the Stress Response Oncoprotein LEDGF/p75 in Human Cancer: A Study of 21 Tumor Types

Oxidative stress-modulated signaling pathways have been implicated in carcinogenesis and therapy resistance. The lens epithelium derived growth factor p75 (LEDGF/p75) is a transcription co-activator that promotes resistance to stress-induced cell death. This protein has been implicated in inflammatory and autoimmune conditions, HIV-AIDS, and cancer. Although LEDGF/p75 is emerging as a stress survival oncoprotein, there is scarce information on its expression in human tumors. The present study was performed to evaluate its expression in a comprehensive panel of human cancers. Transcript expression was examined in the Oncomine cancer gene microarray database and in a TissueScan Cancer Survey Panel quantitative polymerase chain reaction (Q-PCR) array. Protein expression was assessed by immunohistochemistry (IHC) in cancer tissue microarrays (TMAs) containing 1735 tissues representing single or replicate cores from 1220 individual cases (985 tumor and 235 normal tissues). A total of 21 major cancer types were analyzed. Analysis of LEDGF/p75 transcript expression in Oncomine datasets revealed significant upregulation (tumor vs. normal) in 15 out of 17 tumor types. The TissueScan Cancer Q-PCR array revealed significantly elevated LEDGF/p75 transcript expression in prostate, colon, thyroid, and breast cancers. IHC analysis of TMAs revealed significant increased levels of LEDGF/p75 protein in prostate, colon, thyroid, liver and uterine tumors, relative to corresponding normal tissues. Elevated transcript or protein expression of LEDGF/p75 was observed in several tumor types. These results further establish LEDGF/p75 as a cancer-related protein, and provide a rationale for ongoing studies aimed at understanding the clinical significance of its expression in specific human cancers