Distinct Early Molecular Responses to Mutations Causing vLINCL and JNCL Presage ATP Synthase Subunit C Accumulation in Cerebellar Cells

Variant late-infantile neuronal ceroid lipofuscinosis (vLINCL), caused by CLN6 mutation, and juvenile neuronal ceroid lipofuscinosis (JNCL), caused by CLN3 mutation, share clinical and pathological features, including lysosomal accumulation of mitochondrial ATP synthase subunit c, but the unrelated CLN6 and CLN3 genes may initiate disease via similar or distinct cellular processes. To gain insight into the NCL pathways, we established murine wild-type and CbCln6nclf/nclf cerebellar cells and compared them to wild-type and CbCln3Δex7/8/Δex7/8 cerebellar cells. CbCln6nclf/nclf cells and CbCln3Δex7/8/Δex7/8 cells both displayed abnormally elongated mitochondria and reduced cellular ATP levels and, as cells aged to confluence, exhibited accumulation of subunit c protein in Lamp 1-positive organelles. However, at sub-confluence, endoplasmic reticulum PDI immunostain was decreased only in CbCln6nclf/nclf cells, while fluid-phase endocytosis and LysoTracker® labeled vesicles were decreased in both CbCln6nclf/nclf and CbCln3Δex7/8/Δex7/8 cells, though only the latter cells exhibited abnormal vesicle subcellular distribution. Furthermore, unbiased gene expression analyses revealed only partial overlap in the cerebellar cell genes and pathways that were altered by the Cln3Δex7/8 and Cln6nclf mutations. Thus, these data support the hypothesis that CLN6 and CLN3 mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival

Exploring CRM effectiveness: an institutional theory perspective

This study identifies the potential contribution that institutional theory can make to understanding the success of marketing practices. Based on institutional theory, we argue that the effectiveness of marketing practices decreases when firms are motivated to adopt such practices under the influence of institutional pressures originating in firms' environments. However, alignment between a practice and a firm's marketing strategy may buffer against these negative effects. We apply these insights to the case of customer relationship management (CRM). CRM is considered an important way to enhance customer loyalty and firm performance, but it has also been criticized for being expensive and for not living up to expectations. Empirical data from 107 organizations confirm that, in general, adopting CRM for mimetic motives is likely to result in fewer customer insights as a result of using this practice. Our study suggests that institutional theory has much to offer to the investigation of the effectiveness of marketing practices

The effects of customer equity drivers on loyalty across services industries and firms

Customer equity drivers (CEDs)—value equity, brand equity, and relationship equity—positively affect loyalty intentions, but this effect varies across industries and firms. We empirically examine potential industry and firm characteristics that explain why the CEDs–loyalty link varies across services industries and firms in the Netherlands. The results show that (1) some previously assumed industry and firm characteristics have moderating effects while others do not and (2) firm-level advertising expenditures constitute the most crucial moderator because they influence all three loyalty strategies (significant for value equity and brand equity; marginally significant for relationship equity), while three industry contexts (i.e., innovative markets, visibility to others, and complexity of purchase decisions) each influence two of the three loyalty strategies. Our results clearly show that specific industry and firm characteristics affect the effectiveness of specific loyalty strategies

Low octane fuel composition effects on the load range capability of partially premixed combustion

To determine the influence of physical and chemical properties of fuels’ load range capacity in partially premixed combustion, seven fuels have been blended, with a fixed RON70 reactivity. Four of these fuels are blended from refinery streams, with different boiling ranges, aromatic- and bio-content. Furthermore, three ternary mixtures of Toluene, n-Heptane, Ethanol and iso-Octane are used, of which the aromatics (toluene) and oxygenate (ethanol) content are varied. The load range capacity of these fuels is determined based on their fuel efficiency, smoking tendency and its sensitivity to the fuel pressure used, nitrogen oxides emissions, and combustion efficiency and stability at low load and engine speed

Optimizing engine efficiency by balancing dilution, heat release rate and combustion phasing

In this investigation highly diluted engine tests have been conducted to study effects of dilution, heat release rate and combustion phasing on both efficiency and emissions in the Partially Premixed Combustion regime. It has been reported that over the complete phasing range an increase of more than two percent points in indicated efficiency at high load could be expected, with an astonishing 4 to 5 percent points for the low load case. The origins of these increases were sought and found to be caused by improved heat release shapes, combustion efficiencies or heat losses or a combination of these. On the other hand, soot emissions are greatly reduced due to the excess oxygen available, but nitrogen oxide emissions are found to increase: both in concentration and power specific units

Sciatica-like symptoms and the sacroiliac joint: clinical features and differential diagnosis

Item does not contain fulltextPURPOSE: To compare the clinical features of patients with sacroiliac joint (SIJ)-related sciatica-like symptoms to those with sciatica from nerve root compression and to investigate the necessity to perform radiological imaging in patients with sciatica-like symptoms derived from the SIJ. METHODS: Patients with pain radiating below the buttocks with a duration of 4 weeks to 1 year were included. After physical and radiological examinations, a diagnosis of SI joint-related pain, pain due to disk herniation, or a combination of these two causes was made. RESULTS: Patients with SIJ-related leg pain (n = 77/186) were significantly more often female, had shorter statue, a shorter duration of symptoms, and had more often pain radiating to the groin and a history of a fall on the buttocks. Muscle weakness, corkscrew phenomenon, finger-floor distance >/=25 cm, lumbar scoliosis, positive Bragard or Kemp sign, and positive leg raising test were more often present when radiologic nerve root compression was present. Although these investigations may help, MRI of the spine is necessary to discriminate between the groups. CONCLUSIONS: Sciatica-like symptoms derived from the SIJ can clinically mimic a radiculopathy. We suggest to perform a thorough physical examination of the spine, SI joints, and hips with additional radiological tests to exclude other causes