DEVELOPING A PERFORMANCE IMPORTANCE MATRIX FOR A PUBLIC SECTOR BUS TRANSPORT COMPANY: A CASE STUDY

This paper presents a study of comparison of the importance attached by the service providers’ and the customers’ with respect to eighteen service characteristics towards the public transportation services provided by a bus company. The survey was conducted in three bus depots in one division of a state road transport undertaking (SRTU) in south India. The importance the SRTU and the customers attach to these characteristics indicates significant differences. This reveals the existence of a gap between customers’ expectations and the service provided by the company. Finally the customer retention and customer development criteria have been. identified.Performance importance matrix, Customer expectations, Public bus transport, Radar chart.

Molluscicidal effect of biogenic silica and botanical pesticides for the control of Achatina fulica (giant African land snail) and Laevicaulis alte (garden slug)

The molluscicidal effect of silica synthesized from rice husk ash (RHA) on snails (Achatina fulica Bowdich) and slugs (Laevicaulis alte Férussac) was assessed under laboratory conditions. The silica particles derived from RHA were also coated with leaf extracts (botanical pesticides): Azadirachta indica A. Juss, Pongamia pinnata (L.), Nicotiana tabacum (L.), and Calotropis procera (L.). The silica coated with plant extracts and the uncoated silica were applied to the molluscs in dust or slurry form. Inactivation, mortality, and body fluid loss in A. fulica and L. alte were observed over 24 h and recorded. The body fluid losses were 25%–42% for snails and 37%–62% for slugs that had been dusted with silica. During the experiment it was also noted that as the concentration of silica increased (0.15, 0.20, and 0.25 g), the time required for inactivation and mortality was reduced. The dust application was more effective than the slurry. The lower concentration of silica in the slurry (0.05 and 0.10 g) did not have any significant effect on A. fulica or L. alte. For A. fulica the biopesticide-coated silica particles were more effective when coated with neem, followed by tobacco and karanj; for L. alte, the particles were most effective when coated with tobacco, followed by neem and karanj. The plant extract (liquid as well as dry powder) without silica showed no molluscicidal effect on A. fulica and L. alte, except for some temporary inactivation, particularly with tobacco extract. The application of common salt, a practice often used by farmers, was also tested. It was observed that the effects of common salt on A. fulica and L. alte were less significant than those of silica coated with botanical pesticides.

ROLE OF MICROFINANCE INSTITUTIONS IN RURAL DEVELOPMENT

More than subsidies poor need access to credit. Absence of formal employment make them non 'bankable'. This forces them to borrow from local moneylenders at exorbitant interest rates. Many innovative institutional mechanisms have been developed across the world to enhance credit to poor even in the absence of formal mortgage. The present paper discusses conceptual framework of a microfinance institution in India. The successes and failures of various microfinance institutions around the world have been evaluated and lessons learnt have been incorporated in a model microfinance institutional mechanism for India

CIRCLE: Capture In Rich Contextual Environments

Synthesizing 3D human motion in a contextual, ecological environment is important for simulating realistic activities people perform in the real world. However, conventional optics-based motion capture systems are not suited for simultaneously capturing human movements and complex scenes. The lack of rich contextual 3D human motion datasets presents a roadblock to creating high-quality generative human motion models. We propose a novel motion acquisition system in which the actor perceives and operates in a highly contextual virtual world while being motion captured in the real world. Our system enables rapid collection of high-quality human motion in highly diverse scenes, without the concern of occlusion or the need for physical scene construction in the real world. We present CIRCLE, a dataset containing 10 hours of full-body reaching motion from 5 subjects across nine scenes, paired with ego-centric information of the environment represented in various forms, such as RGBD videos. We use this dataset to train a model that generates human motion conditioned on scene information. Leveraging our dataset, the model learns to use ego-centric scene information to achieve nontrivial reaching tasks in the context of complex 3D scenes. To download the data please visit https://stanford-tml.github.io/circle_dataset/

Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components

gamma-Secretase, which is responsible for the intramembranous cleavage of Alzheimer beta-amyloid precursor protein and the signaling receptor Notch, is a multiprotein complex consisting of at least four components: presenilin ( PS); nicastrin (Nct); APH-1 ( anterior pharynx-defective-1); and presenilin enhancer-2 (PEN-2). Presenilin 1 (PS1) is known to be essential for the stability, interaction, and trafficking of the other PS1/gamma-secretase components. However, the precise functions of the other components remain elusive. Here, we investigated the functions of Nct within the PS1/gamma-secretase complex. We demonstrated that the loss of Nct expression in the embryonic fibroblast cells ( Nct KO cells) results in dramatically decreased levels of APH-1, PEN-2, and PS1 fragments accompanied by a significant accumulation of full-length PS1. In the absence of Nct, PEN-2 and full-length PS1 are subjected to proteasome-mediated degradation, whereas the degradation of APH-1 is mediated by both proteasomal and lysosomal pathways. Unlike the case of wild type cells in which the gamma-secretase complex mainly locates in the trans-Golgi network, the majority of residual PEN-2, APH-1, and the uncleaved full-length PS1 in Nct KO cells reside in the endoplasmic reticulum, which remain associated with each other in the absence of Nct. Interestingly, significant amounts of full-length PS1 and PEN-2, but not APH-1, are detected on the plasma membrane in Nct KO cells, suggesting the Nct-independent cell surface delivery of the PEN-2 center dot PS1. Finally, the diminished PEN-2 protein level in Nct-deficient cells can be partially restored by overexpression of exogenous PS1, APH-1, or PEN-2 individually or collectively, indicating a dispensable role for Nct in controlling PEN-2 level. Taken together, our study demonstrates a critical role of Nct in the stability and proper intracellular trafficking of other components of the PS1/ gamma-secretase complex but not in maintaining the association of PEN-2, APH-1, and full-length PS1

Transthyretin Protects against A-Beta Peptide Toxicity by Proteolytic Cleavage of the Peptide: A Mechanism Sensitive to the Kunitz Protease Inhibitor

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid β-peptide (A-Beta) in the brain. Transthyretin (TTR) is a tetrameric protein of about 55 kDa mainly produced in the liver and choroid plexus of the brain. The known physiological functions of TTR are the transport of thyroid hormone T4 and retinol, through binding to the retinol binding protein. TTR has also been established as a cryptic protease able to cleave ApoA-I in vitro. It has been described that TTR is involved in preventing A-Beta fibrilization, both by inhibiting and disrupting A-Beta fibrils, with consequent abrogation of toxicity. We further characterized the nature of the TTR/A-Beta interaction and found that TTR, both recombinant or isolated from human sera, was able to proteolytically process A-Beta, cleaving the peptide after aminoacid residues 1, 2, 3, 10, 13, 14,16, 19 and 27, as determined by mass spectrometry, and reversed phase chromatography followed by N-terminal sequencing. A-Beta peptides (1–14) and (15–42) showed lower amyloidogenic potential than the full length counterpart, as assessed by thioflavin binding assay and ultrastructural analysis by transmission electron microscopy. A-Beta cleavage by TTR was inhibited in the presence of an αAPP peptide containing the Kunitz Protease Inhibitor (KPI) domain but not in the presence of the secreted αAPP derived from the APP isoform 695 without the KPI domain. TTR was also able to degrade aggregated forms of A-Beta peptide. Our results confirmed TTR as a protective molecule in AD, and prompted A-Beta proteolysis by TTR as a protective mechanism in this disease. TTR may prove to be a useful therapeutic agent for preventing or retarding the cerebral amyloid plaque formation implicated in AD pathology

Amyloid Precursor Protein Is Trafficked and Secreted via Synaptic Vesicles

A large body of evidence has implicated amyloid precursor protein (APP) and its proteolytic derivatives as key players in the physiological context of neuronal synaptogenesis and synapse maintenance, as well as in the pathology of Alzheimer's Disease (AD). Although APP processing and release are known to occur in response to neuronal stimulation, the exact mechanism by which APP reaches the neuronal surface is unclear. We now demonstrate that a small but relevant number of synaptic vesicles contain APP, which can be released during neuronal activity, and most likely represent the major exocytic pathway of APP. This novel finding leads us to propose a revised model of presynaptic APP trafficking that reconciles existing knowledge on APP with our present understanding of vesicular release and recycling

Receptor-Associated Protein (RAP) Plays a Central Role in Modulating Aβ Deposition in APP/PS1 Transgenic Mice

BACKGROUND: Receptor associated protein (RAP) functions in the endoplasmic reticulum (ER) to assist in the maturation of several membrane receptor proteins, including low density lipoprotein receptor-related protein (LRP) and lipoprotein receptor 11 (SorLA/LR11). Previous studies in cell and mouse model systems have demonstrated that these proteins play roles in the metabolism of the amyloid precursor protein (APP), including processes involved in the generation, catabolism and deposition of beta-amyloid (Abeta) peptides. METHODOLOGY/PRINCIPAL FINDINGS: Mice transgenic for mutant APPswe and mutant presenilin 1 (PS1dE9) were mated to mice with homozygous deletion of RAP. Unexpectedly, mice that were homozygous null for RAP and transgenic for APPswe/PS1dE9 showed high post-natal mortality, necessitating a shift in focus to examine the levels of amyloid deposition in APPswe/PS1dE9 that were hemizygous null for RAP. Immunoblot analysis confirmed 50% reductions in the levels of RAP with modest reductions in the levels of proteins dependent upon RAP for maturation [LRP trend towards a 20% reduction ; SorLA/LR11 statistically significant 15% reduction (p<0.05)]. Changes in the levels of these proteins in the brains of [APPswe/PS1dE9](+/-)/RAP(+/-) mice correlated with 30-40% increases in amyloid deposition by 9 months of age. CONCLUSIONS/SIGNIFICANCE: Partial reductions in the ER chaperone RAP enhance amyloid deposition in the APPswe/PS1dE9 model of Alzheimer amyloidosis. Partial reductions in RAP also affect the maturation of LRP and SorLA/LR11, which are each involved in several different aspects of APP processing and Abeta catabolism. Together, these findings suggest a central role for RAP in Alzheimer amyloidogenesis

RETRACTED ARTICLE: Age-dependent Increase in Desmosterol Restores DRM Formation and Membrane-related Functions in Cholesterol-free DHCR24−/− Mice

Cholesterol is a prominent modulator of the integrity and functional activity of physiological membranes and the most abundant sterol in the mammalian brain. DHCR24-knock-out mice lack cholesterol and accumulate desmosterol with age. Here we demonstrate that brain cholesterol deficiency in 3-week-old DHCR24−/− mice was associated with altered membrane composition including disrupted detergent-resistant membrane domain (DRM) structure. Furthermore, membrane-related functions differed extensively in the brains of these mice, resulting in lower plasmin activity, decreased β-secretase activity and diminished Aβ generation. Age-dependent accumulation and integration of desmosterol in brain membranes of 16-week-old DHCR24−/− mice led to the formation of desmosterol-containing DRMs and rescued the observed membrane-related functional deficits. Our data provide evidence that an alternate sterol, desmosterol, can facilitate processes that are normally cholesterol-dependent including formation of DRMs from mouse brain extracts, membrane receptor ligand binding and activation, and regulation of membrane protein proteolytic activity. These data indicate that desmosterol can replace cholesterol in membrane-related functions in the DHCR24−/− mouse