The Human Lipodystrophy Gene BSCL2/Seipin May Be Essential for Normal Adipocyte Differentiation

OBJECTIVE—Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder featuring near complete absence of adipose tissue. Remarkably, although the causative gene, BSCL2, has been known for several years, its molecular function and its role in adipose tissue development have not been elucidated. Therefore, we examined whether BSCL2 is involved in the regulation of adipocyte differentiation and the mechanism whereby pathogenic mutations in BSCL2 cause lipodystrophy

Attitudes and perceptions regarding entrepreneurship around the world : a cluster analysis approach

Nowadays it is believed that entrepreneurship could be a driving force in growth and development. For the achievement of a relevant national entrepreneurship rate the social and economic business environment can be crucial. However, despite the international attention given to entrepreneurship, it is not known if it is a global phenomenon or if there are particular regions where the entrepreneurial activity is specially recognized by society. Applying cluster analysis statistical techniques to a dataset gathered by the Global Entrepreneurship Monitor (GEM) and that includes, in 2010, 59 countries this paper intends to identify groups of countries with the same population attitude and perception regarding entrepreneurship

Attitudes and perceptions regarding entrepreneurship around the world : a cluster analysis approach

Nowadays it is believed that entrepreneurship could be a driving force in growth and develop-ment. For the achievement of a relevant national entrepreneurship rate the social and economic business environment can be crucial. However, despite the international attention given to entrepreneurship, it is not known if it is a global phenomenon or if there are particular regions where the entrepreneurial activity is specially recognized by society. Applying cluster analysis statistical techniques to a dataset gathered by the Global Entrepreneurship Monitor (GEM) and that includes, in 2010, 59 countries this paper intends to identify groups of countries with the same population attitude and perception regarding entrepreneurship

Death of the high street: identification, prevention, reinvention

Location is of paramount importance within the retail sector, yet defining locational obsolescence remains overlooked, despite significant concerns over the viability of parts of the complex sector. This paper reviews the existing literature and, through this, explores retail locational obsolescence, including the multi-spatial nature of the driving forces that range from the global economy, local markets and submarkets, to individual property-specific factors; and, crucially, the need to disentangle locational obsolescence from other important concepts such as depreciation and functional obsolescence that are often mistakenly used. Through this, a conceptual model, definition and diagnostic criteria are presented to guide future studies, policy development and the allocation of resources. Importantly, three stages are presented to enable the operationalization of the model, essential to future academic and industry studies as well as the ongoing development of policy in this economically important, complex and contentious area

High Tumour Cannabinoid CB1 Receptor Immunoreactivity Negatively Impacts Disease-Specific Survival in Stage II Microsatellite Stable Colorectal Cancer

BACKGROUND: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. METHODOLOGY/PRINCIPAL FINDINGS: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and ≥2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB(1)IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 85±5 and 66±8%; tumour interior, 86±4% and 63±8% for the CB(1)IR<2 and CB(1)IR≥2 groups, respectively. CONCLUSIONS/SIGNIFICANCE: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients

Reversible Disruption of Pre-Pulse Inhibition in Hypomorphic-Inducible and Reversible CB1-/- Mice

Although several genes are implicated in the pathogenesis of schizophrenia, in animal models for such a severe mental illness only some aspects of the pathology can be represented (endophenotypes). Genetically modified mice are currently being used to obtain or characterize such endophenotypes. Since its cloning and characterization CB1 receptor has increasingly become of significant physiological, pharmacological and clinical interest. Recently, its involvement in schizophrenia has been reported. Among the different approaches employed, gene targeting permits to study the multiple roles of the endocannabinoid system using knockout (-/-) mice represent a powerful model but with some limitations due to compensation. To overcome such a limitation, we have generated an inducible and reversible tet-off dependent tissue-specific CB1-/- mice where the CB1R is re-expressed exclusively in the forebrain at a hypomorphic level due to a mutation (IRh-CB1-/-) only in absence of doxycycline (Dox). In such mice, under Dox+ or vehicle, as well as in wild-type (WT) and CB1-/-, two endophenotypes motor activity (increased in animal models of schizophrenia) and pre-pulse inhibition (PPI) of startle reflex (disrupted in schizophrenia) were analyzed. Both CB1-/- and IRh-CB1-/- showed increased motor activity when compared to WT animals. The PPI response, unaltered in WT and CB1-/- animals, was on the contrary highly and significantly disrupted only in Dox+ IRh-CB1-/- mice. Such a response was easily reverted after either withdrawal from Dox or haloperidol treatment. This is the first Inducible and Reversible CB1-/- mice model to be described in the literature. It is noteworthy that the PPI disruption is not present either in classical full CB1-/- mice or following acute administration of rimonabant. Such a hypomorphic model may provide a new tool for additional in vivo and in vitro studies of the physiological and pathological roles of cannabinoid system in schizophrenia and in other psychiatric disorders

Once the shovel hits the ground : Evaluating the management of complex implementation processes of public-private partnership infrastructure projects with qualitative comparative analysis

Much attention is being paid to the planning of public-private partnership (PPP) infrastructure projects. The subsequent implementation phase – when the contract has been signed and the project ‘starts rolling’ – has received less attention. However, sound agreements and good intentions in project planning can easily fail in project implementation. Implementing PPP infrastructure projects is complex, but what does this complexity entail? How are projects managed, and how do public and private partners cooperate in implementation? What are effective management strategies to achieve satisfactory outcomes? This is the fi rst set of questions addressed in this thesis. Importantly, the complexity of PPP infrastructure development imposes requirements on the evaluation methods that can be applied for studying these questions. Evaluation methods that ignore complexity do not create a realistic understanding of PPP implementation processes, with the consequence that evaluations tell us little about what works and what does not, in which contexts, and why. This hampers learning from evaluations. What are the requirements for a complexity-informed evaluation method? And how does qualitative comparative analysis (QCA) meet these requirements? This is the second set of questions addressed in this thesis

Liquidus Temperature Measurements for Metallurgical Slags

A technique is being developed for the fast measurement of the liquidus temperature of synthetic and industrial slags. The technique involves using a type K thermocouple centred within a nickel cylinder to record the heating profile after immersion of the cylinder into a molten bath. Upon immersion of the cold cylinder into the bath, a layer of slag freezes onto the surface. When this melts away, the rate of heating of the cylinder increases, and the point of this increase provides an estimate of the liquidus temperature of the slag. The temperature data are logged and analysed using a PC-based system, to detect this point The technique is illustrated here for iron saturated fayalite slags with various additions of lime and magnesia, as well as for industrial smelting slags

Recovery of copper and cobalt from industrial slag by top-submerged injection of gaseous reductants

Slag from an electric slag cleaning furnace was injected with methane and air mixtures to facilitate the recovery of copper and cobalt. The effects of methane-to-air ratio, gas flow rate and temperature on the reduction and metal separation were investigated. The results showed that over 90 percent copper and up to 60 percent cobalt could be recovered from the slag with a gas utilization of around 70 percent, as calculated by thermodynamic simulation. Methane-to-air ratio was a major factor affecting the rate of reduction under the present experimental conditions. Further, injection of gaseous reductants greatly enhanced the coalescence and settling of entrained metal droplets. A reduction mechanism is proposed and the factors influencing the coalescence of copper droplets are discussed