Defining alcohol-related phenotypes in humans. The Collaborative Study on the Genetics of Alcoholism.

Alcoholism is a disease that runs in families and results at least in part from genetic risk factors. The Collaborative Study on the Genetics of Alcoholism (COGA) is a Federally funded effort to identify and characterize those genetic factors. The study involves more than 1,000 alcoholic subjects and their families, with researchers conducting comprehensive psychological, physiological, electrophysiological, and genetic analyses of the participants. These analyses have identified several traits, or phenotypes, that appear to be genetically determined, such as the presence of alcohol dependence, the level of response to alcohol, the presence of coexisting depression, or the maximum number of drinks a person consumes per occasion. Genetic analyses have identified regions on several chromosomes that are associated with these phenotypes and need to be studied further

Quantized Densely Connected U-Nets for Efficient Landmark Localization

In this paper, we propose quantized densely connected U-Nets for efficient visual landmark localization. The idea is that features of the same semantic meanings are globally reused across the stacked U-Nets. This dense connectivity largely improves the information flow, yielding improved localization accuracy. However, a vanilla dense design would suffer from critical efficiency issue in both training and testing. To solve this problem, we first propose order-K dense connectivity to trim off long-distance shortcuts; then, we use a memory-efficient implementation to significantly boost the training efficiency and investigate an iterative refinement that may slice the model size in half. Finally, to reduce the memory consumption and high precision operations both in training and testing, we further quantize weights, inputs, and gradients of our localization network to low bit-width numbers. We validate our approach in two tasks: human pose estimation and face alignment. The results show that our approach achieves state-of-the-art localization accuracy, but using ~70% fewer parameters, ~98% less model size and saving ~75% training memory compared with other benchmark localizers. The code is available at https://github.com/zhiqiangdon/CU-Net.Comment: ECCV201

Four Work-Ins by Australian Journalists, 1944-80

During industrial disputes with employers between 1944 and 1980 the Australian Journalist's Association occasionally turned to the tactic of the work-in, producing wild cat newspapers during strikes in Sydney. These newspapers (The News, and The Clarion) exemplified problematic elements of the work-in as a working-class strategy. While single incident studies of the work-in have been conducted in Australia, the Australian Journalist Association work-ins present a time series of struggle. This time series allows for a broader evaluation of the radical content of the work-in and indicates that the tactic can become systematised, less radical, and less participatory when not connected to a broader generation of workplace radical behaviour by workers. In short: the work-in, much like the strike or go slow, can become a tame cat tactic – it is not inherently transgressive or opposed to capitalist production. Expectedly, the first work-ins were more radical in scope, presenting a newspaper which fully duplicated the commodity produced under capitalist control and in some ways exceeded the scope presented by capitalist organised journalism in both a material and a cultural sense. However, this radical economic potential dissipated by the end of the time series of work-ins. Instead of providing an alternative commodity fit for market, the tactic produced propaganda pieces aimed primarily at the members of the community who would be predisposed to favour the journalist's case. The 1980s Clarion was not a daily newspaper of news, sport, racing, women's interest, classifieds, and general opinion. This change will be explained in terms of human causes such as skills loss, production process causes such as computerisation and wire services, and broader social causes such as the changing role of the newspaper in Australian society.The symposium is organised on behalf of AAHANZBS by the Business and Labour History Group, The University of Sydney, with the financial support of the University’s Faculty of Economics and Business

The genetic basis of DOORS syndrome: an exome-sequencing study.

Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. We aimed to identify the genetic basis of this syndrome by sequencing most coding exons in affected individuals

Description of the data from the Collaborative Study on the Genetics of Alcoholism (COGA) and single-nucleotide polymorphism genotyping for Genetic Analysis Workshop 14

The data provided to the Genetic Analysis Workshop 14 (GAW 14) was the result of a collaboration among several different groups, catalyzed by Elizabeth Pugh from The Center for Inherited Disease Research (CIDR) and the organizers of GAW 14, Jean MacCluer and Laura Almasy. The DNA, phenotypic characterization, and microsatellite genomic survey were provided by the Collaborative Study on the Genetics of Alcoholism (COGA), a nine-site national collaboration funded by the National Institute of Alcohol and Alcoholism (NIAAA) and the National Institute of Drug Abuse (NIDA) with the overarching goal of identifying and characterizing genes that affect the susceptibility to develop alcohol dependence and related phenotypes. CIDR, Affymetrix, and Illumina provided single-nucleotide polymorphism genotyping of a large subset of the COGA subjects. This article briefly describes the dataset that was provided

Potentiation of anti-cancer drug activity at low intratumoral pH induced by the mitochondrial inhibitor m-iodobenzylguanidine (MIBG) and its analogue benzylguanidine (BG)

Tumour-selective acidification is of potential interest for enhanced therapeutic gain of pH sensitive drugs. In this study, we investigated the feasibility of a tumour-selective reduction of the extracellular and intracellular pH and their effect on the tumour response of selected anti-cancer drugs. In an in vitro L1210 leukaemic cell model, we confirmed enhanced cytotoxicity of chlorambucil at low extracellular pH conditions. In contrast, the alkylating drugs melphalan and cisplatin, and bioreductive agents mitomycin C and its derivative EO9, required low intracellular pH conditions for enhanced activation. Furthermore, a strong and pH-independent synergism was observed between the pH-equilibrating drug nigericin and melphalan, of which the mechanism is unclear. In radiation-induced fibrosarcoma (RIF-1) tumour-bearing mice, the extracellular pH was reduced by the mitochondrial inhibitor m-iodobenzylguanidine (MIBG) or its analogue benzylguanidine (BG) plus glucose. To simultaneously reduce the intracellular pH, MIBG plus glucose were combined with the ionophore nigericin or the Na+/H+ exchanger inhibitor amiloride and the Na+-dependent HCO3−/Cl−exchanger inhibitor 4,4′-diisothiocyanostilbene-2,2′-disulphonic acid (DIDS). Biochemical studies confirmed an effective reduction of the extracellular pH to approximately 6.2, and anti-tumour responses to the interventions indicated a simultaneous reduction of the intracellular pH below 6.6 for at least 3 h. Combined reduction of extra- and intracellular tumour pH with melphalan increased the tumour regrowth time to 200% of the pretreatment volume from 5.7 ± 0.6 days for melphalan alone to 8.1 ± 0.7 days with pH manipulation (P< 0.05). Mitomycin C related tumour growth delay was enhanced by the combined interventions from 3.8 ± 0.5 to 5.2 ± 0.5 days (P< 0.05), but only in tumours of relatively large sizes. The interventions were non-toxic alone or in combination with the anti-cancer drugs and did not affect melphalan biodistribution. In conclusion, we have developed non-toxic interventions for sustained and selective reduction of extra- and intracellular tumour pH which potentiated the tumour responses to selected anti-cancer drugs. 1999 Cancer Research Campaig

Algorithms for learning parsimonious context trees

Parsimonious context trees, PCTs, provide a sparse parameterization of conditional probability distributions. They are particularly powerful for modeling context-specific independencies in sequential discrete data. Learning PCTs from data is computationally hard due to the combinatorial explosion of the space of model structures as the number of predictor variables grows. Under the score-and-search paradigm, the fastest algorithm for finding an optimal PCT, prior to the present work, is based on dynamic programming. While the algorithm can handle small instances fast, it becomes infeasible already when there are half a dozen four-state predictor variables. Here, we show that common scoring functions enable the use of new algorithmic ideas, which can significantly expedite the dynamic programming algorithm on typical data. Specifically, we introduce a memoization technique, which exploits regularities within the predictor variables by equating different contexts associated with the same data subset, and a bound-and-prune technique, which exploits regularities within the response variable by pruning parts of the search space based on score upper bounds. On real-world data from recent applications of PCTs within computational biology the ideas are shown to reduce the traversed search space and the computation time by several orders of magnitude in typical cases.Peer reviewe