2,541 research outputs found

    A Fresh Start or the Devil You Know? Examining Relationships Between Release Location Choices, Community Experiences, and Recidivism for High-Risk Parolees

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    This study investigated the effects of residential relocation in a sample of 282 high-risk male offenders paroled from New Zealand prisons. Initially we compared those returning to their old neighborhoods (devil you know) and those released to a new location (fresh start). This second category was then further divided: those released to a new location voluntarily (fresh start-voluntary) versus those forced to start anew at the behest of the parole board that was releasing them (fresh start-duress). All three categories were then compared on the quality of their community experiences and recidivism. Results indicated that parolees returning by choice to either their old neighborhood or a new location each were reconvicted in the first year after release at approximately the same rate; however, parolees relocating to a new area at the direction of the parole board (under duress) were reconvicted at a higher rate than those in either of the voluntary location categories. Significant group differences in ratings of community life quality were few, but there were some indications that compared with those choosing to return to a familiar location, making a voluntary residential relocation may lead to better parole experiences, particularly in terms of avoiding criminal peers, and that making a residential relocation under duress may lead to poorer parole experiences than for those returning to a familiar location

    The Unfulfilled Potential of Data-Driven Decision Making in Agile Software Development

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    With the general trend towards data-driven decision making (DDDM), organizations are looking for ways to use DDDM to improve their decisions. However, few studies have looked into the practitioners view of DDDM, in particular for agile organizations. In this paper we investigated the experiences of using DDDM, and how data can improve decision making. An emailed questionnaire was sent out to 124 industry practitioners in agile software developing companies, of which 84 answered. The results show that few practitioners indicated a widespread use of DDDM in their current decision making practices. The practitioners were more positive to its future use for higher-level and more general decision making, fairly positive to its use for requirements elicitation and prioritization decisions, while being less positive to its future use at the team level. The practitioners do see a lot of potential for DDDM in an agile context; however, currently unfulfilled

    Bifunctional chalcogen linkers for the stepwise generation of multimetallic assemblies and functionalized nanoparticles

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    The disulfide ligand (SC6H4CO2H-4)2 acts as a simple but versatile linker for a range of group 8 transition metals through reaction of the oxygen donors. This leads to a range of homobimetallic ruthenium and osmium alkenyl compounds, [{M(CH═CHR)(CO)(PPh3)2(O2CC6H4S-4)}2] (M = Ru, Os; R = C6H4Me-4). Additional metal-based functionality can be added through the use of precursors incorporating rhenium bipyridine units (R = (bpy)ReCl(CO)3). The more robust diphosphine ligands in [{Ru(dppm)2(O2CC6H4S-4)}2](2+) (dppm = diphenylphosphinomethane) allow reduction of the disulfide bond with sodium borohydride to yield the thiol complex [Ru(O2CC6H4SH-4)(dppm)2](+). This complex reacts with [AuCl(PPh3)] to afford the bimetallic compound [Ru(dppm)2(O2CC6H4S-4)Au(PPh3)](+). However, an improved route to the same and related heterobimetallic compounds is provided by the reaction of cis-[RuCl2(dppm)2] with [Au(SC6H4CO2H-4)(L)] (L = PPh3, PCy3, PMe3, IDip) in the presence of base and NH4PF6 (IDip = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene). The heterotrimetallic compound [Au(SC6H4CO2Ru(dppm)2)2](+) is accessible through the reaction of the homoleptic gold(I) dithiolate [Au(SC6H4CO2H-4)2]PPN (PPN = bis(triphenylphosphine)iminium) with cis-[RuCl2(dppm)2]. Without departure from the same methodology, greater complexity can be incorporated into the system to provide the penta- and heptametallic assemblies [(dppf){AuSC6H4CO2Ru(dppm)2}2](2+) and [(dppf){AuSC6H4CO2Os(CH═CH-bpyReCl(CO)3)(CO)(PPh3)2}2]. The same stepwise approach provides the dinuclear organometallic complexes [(L)Au(SC6H4CO2-4)M(CH═CHC6H4Me-4)(CO)(PPh3)2] (M = Ru, Os; L = PPh3, IDip). Complexes containing three metals from different groups of the periodic table [(L)Au(SC6H4CO2-4)M{CH═CH-bpyReCl(CO)3}(CO)(PPh3)2] (M = Ru, Os) can also be prepared, with one ruthenium example (L = PPh3) being structurally characterized. In order to illustrate the versatility of this approach, the synthesis and characterization (IR and NMR spectroscopy, TEM, EDS, and TGA) of the functionalized gold and palladium nanoparticles Au@[SC6H4CO2Ru(dppm)2](+) and Pd@[SC6H4CO2Ru(dppm)2](+) is reported

    Acute changes in liver tumour perfusion measured non-invasively with arterial spin labelling

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    BACKGROUND: Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting (or modifying) therapies. In this study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was investigated to measure acute changes in perfusion of colorectal cancer in the liver, in response to vascular disruption therapy with OXi4503. METHODS: SW1222 and LS174T tumours were established in the liver of MF1 nu/nu mice via intrasplenic injection. Perfusion and R2(*) MRI measurements were acquired with an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg(-1) OXi4503. RESULTS: A significant decrease in SW1222 tumour perfusion was observed (-43±33%, P<0.005). LS174T tumours had a significantly lower baseline level of perfusion. Intrinsic susceptibility MRI showed a significant increase in R2(*) in LS174T tumours (28±25%, P<0.05). An association was found between the change in tumour perfusion and the proximity to large vessels, with pre-treatment blood flow predictive of subsequent response. Histological evaluation confirmed the onset of necrosis and evidence of heterogeneous response between tumour deposits. CONCLUSIONS: Hepatic ASL-MRI can detect acute response to targeted tumour vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has potential for use in a clinical setting

    Noncommutative generalizations of theorems of Cohen and Kaplansky

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    This paper investigates situations where a property of a ring can be tested on a set of "prime right ideals." Generalizing theorems of Cohen and Kaplansky, we show that every right ideal of a ring is finitely generated (resp. principal) iff every "prime right ideal" is finitely generated (resp. principal), where the phrase "prime right ideal" can be interpreted in one of many different ways. We also use our methods to show that other properties can be tested on special sets of right ideals, such as the right artinian property and various homological properties. Applying these methods, we prove the following noncommutative generalization of a result of Kaplansky: a (left and right) noetherian ring is a principal right ideal ring iff all of its maximal right ideals are principal. A counterexample shows that the left noetherian hypothesis cannot be dropped. Finally, we compare our results to earlier generalizations of Cohen's and Kaplansky's theorems in the literature.Comment: 41 pages. To appear in Algebras and Representation Theory. Minor changes were made to the numbering system, in order to remain consistent with the published versio

    Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

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    BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

    A G-quadruplex-binding compound showing anti-tumour activity in an in vivo model for pancreatic cancer

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    We report here that a tetra-substituted naphthalene-diimide derivative (MM41) has significant in vivo anti-tumour activity against the MIA PaCa-2 pancreatic cancer xenograft model. IV administration with a twice-weekly 15 mg/kg dose produces ca 80% tumour growth decrease in a group of tumour-bearing animals. Two animals survived tumour-free after 279 days. High levels of MM41 are rapidly transported into cell nuclei and were found to accumulate in the tumour. MM41 is a quadruplex-interactive compound which binds strongly to the quadruplexes encoded in the promoter sequences of the BCL-2 and k-RAS genes, both of which are dis-regulated in many human pancreatic cancers. Levels of BCL-2 were reduced by ca 40% in tumours from MM41-treated animals relative to controls, consistent with BCL-2 being a target for MM41. Molecular modelling suggests that MM41 binds to a BCL-2 quadruplex in a manner resembling that previously observed in co-crystal structures with human telomeric quadruplexes. This supports the concept that MM41 (and by implication other quadruplex-targeting small molecules) can bind to quadruplex-forming promoter regions in a number of genes and down-regulate their transcription. We suggest that quadruplexes within those master genes that are up-regulated drivers for particular cancers, may be selective targets for compounds such as MM41

    The unfulfilled potential of data-driven decision making in agile software development

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    With the general trend towards data-driven decision making (DDDM), organizations are looking for ways to use DDDM to improve their decisions. However, few studies have looked into the practitioners view of DDDM, in particular for agile organizations. In this paper we investigated the experiences of using DDDM, and how data can improve decision making. An emailed questionnaire was sent out to 124 industry practitioners in agile software developing companies, of which 84 answered. The results show that few practitioners indicated a wide-spread use of DDDM in their current decision making practices. The practitioners were more positive to its future use for higher-level and more general decision making, fairly positive to its use for requirements elicitation and prioritization decisions, while being less positive to its future use at the team level. The practitioners do see a lot of potential for DDDM in an agile context; however, currently unfulfilled

    How Do Bone Marrow Lesions Cause Osteoarthritis Pain? a Structural and Functional Tissue-Based Study

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    Background/Purpose: Susceptibility to ankylosing spondylitis (AS) is primarily genetic; thus far 113 susceptibility variants for AS have been identified. However, most of the AS associated SNPs do not directly affect protein-coding genes. Studies of disease- and trait-associated SNPs suggest they may act by affecting gene regulatory regions in specific cell types or tissues. Therefore, identifying the AS relevant cell types is crucial for further mechanistic studies. Methods: We applied several bioinformatics methods to utilize epigenetic, gene and protein expression information to identify the primary relevant cell types through which genetic variants associated with AS operate. In total, there are 113 AS associated loci; 39 of them show genome-wide significance in AS-only analyses, whereas the remainder are genome-wide significant in analyses leveraging pleiotrophy with other related diseases (Crohn’s disease (CD), psoriasis, primary sclerosing cholangitis (PSC) and ulcerative colitis (UC))1. Results: AS-associated SNPs are disproportionately found in regions bearing epigenetic marks indicating transcriptional activity found in immune cell types including monocytes, CD4+ and CD8+ T cells, NK cells, regulatory T cells, and B cells. Gene expression studies showed enrichment of AS associated loci in genes specifically expressed in monocytes and NK cells while protein expression study shows protein products of AS associated loci were significantly enriched in CD8+ T cells. Epigenetic analyses also showed evidence that AS-associated signals operate in gut cell types including in mucosa from the small intestine, sigmoid colon and rectum. These findings particularly relate to pleiotropic loci also associated with IBD, psoriasis, and PSC. Conclusion: These findings highlight the role of key immune cell types in the mechanism by which genetic associations with AS drive the disease, as well as providing further evidence for the involvement of the gut in the pathogenesis of AS. 1Ellinghaus D. at al, Nature Genetics 201
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