A conserved mechanism of Hedgehog gradient formation by lipid modifications

Members of the Hedgehog (Hh) family of proteins are conserved morphogens that modulate cell fates in target tissues in different developmental systems. Dysregulation of Hh signaling results in a wide range of human diseases. The mature Hh is modified by lipids in two places, with palmitate at the N-terminus and cholesterol at the C-terminus. The lipid modifications are essential to the proper secretion and spreading of the morphogen throughout the extracellular matrix, interacting with heparan sulfate proteoglycans. However, the role of lipid modifications in regulating the range and activity of Hh proteins remains controversial. Here, we aim to resolve this issue by providing a model that is consistent with current and past reports. We propose that the cholesterol moiety functions to restrict the dilution and deregulated spread of the morphogen in the extracellular spaceWe also thank the support of the Spanish D.G.I.C.Y.T, grant BFU2005-04183 (I.G.), the Fundación Areces for an institutional grant (I.G.), National Institutes of Health grant HD049667 (C.C.) and March of Dimes foundation (C.C)Peer reviewe

Analysis of personnel interview questions for student affairs positions at land-grant institutions

Personnel issues have always played an important part in any operation. There is no denying the fact that proper selection and placement of individuals could be the key to an organization\u27s success. This study was made to compare the variables assessed and questions asked during final interviews to evaluate the candidates for open positions in the division of student affairs at all public land-grant institutions; The theoretical base for the study stressed the necessity of comparing applicants\u27 abilities. Variables being considered during the interviews were categorized as job knowledge, professional attitude, personal qualities, interpersonal skills and miscellaneous. Using these variables as a guide a survey-questionnaire was constructed to collect data from the pre-determined population; Based on the content analysis of the data collected, a generic model of a set of interview questions was proposed which includes a total of 15 items

Implement Innovative Proactive-Service-Center to Enhance Service Performance in Customer Site

How to more efficiently and effectively enhance service performance is an on-going challenge to any service team. A new service model, Proactive-Service-Center (P-S-C), is developed since Feb’01. As a result, the service performance results are improved in terms of same day issue closure rate, issue response time and system uptime. The P-S-C is not only an innovative way to enhance service performance but also a systematic way to build-up engineers\u27 trouble-shooting capability. In the old service situation, the information flows randomly among customer engineers, customer section managers, AMT engineers, and AMT site managers. The average time spent is around two hours from Issue Happened to Dedicated Engineer on site. Customer and AMT engineers are running around like a chicken without head. The information flows inefficiently and ineffectively among customer engineers, section managers, AMT engineers and site managers. The detailed solutions are not documented and remained in the engineers\u27 heads. In the PSC model, the information flows automatically from the system which is down to the customer Server then to the PSC Server and the dedicated AMT engineer is automatically informed. The information flows efficiently and effectively. The actions done are then systematically entered and documented in PSC and a monthly analysis report is generated and provided to customers. The cost savings of PSC can be estimated indirectly. The issue response time is reduced from 2 hours to 58 minutes (reduced by 62 minutes). This translates to the increase of system uptime by 62 minutes. This will bring cost savings. In addition, the issue closure rate is improved from 50% to 85% (improved by 35%). This also translates to the increase of system uptime. The system uptime enhancement is cost savings. Three areas which need improvement are identified to be Technology, People and Process. Technology: Internet is used and many auto functions (for example, reminding, reporting) are built-in to enhance the capability. People: Dedicated Engineer Matrix is built-in PSC and the right engineer can be reached at the right time in the most efficient manner. Process: Process is real time and systematic with clear R&R defined to ensure efficiency and experience build-up in the future

Phase Distribution and Phase Correlation of Financial Time Series

Scaling, phase distribution and phase correlation of financial time series are investigated based on the Dow Jones Industry Average (DJIA) and NASDAQ 10-minute intraday data for a period from Aug. 1 1997 to Dec. 31 2003. The returns of the two indices are shown to have nice scaling behaviors and belong to stable distributions according to the criterion of Levy's alpha stable distribution condition. A novel approach catching characteristic features of financial time series based on the concept of instantaneous phase is further proposed to study phase distribution and correlation. The analysis of phase distribution concludes return time series fall into a class which is different from other non-stationary time series. The correlation between returns of the two indices probed by the distribution of phase difference indicates there was a remarkable change of trading activities after the event of 911 attack, and this change persisted in later trading activities.Phase Distribution, High Frequency Data, Scaling Analysis, Levy Distribution, Stock Market, Frequency Variant

SPT5 affects the rate of mRNA degradation and physically interacts with CCR4 but does not control mRNA deadenylation

The CCR4-NOT complex has been shown to have multiple roles in mRNA metabolism, including that of transcriptional elongation, mRNA transport, and nuclear exosome function, but the primary function of CCR4 and CAF1 is in the deadenylation and degradation of cytoplasmic mRNA. As previous genetic analysis supported an interaction between SPT5, known to be involved in transcriptional elongation, and that of CCR4, the physical association of SPT5 with CCR4 was examined. A two-hybrid screen utilizing the deadenylase domain of CCR4 as a bait identified SPT5 as a potential interacting protein. SPT5 at its physiological concentration was shown to immunoprecipitate CCR4 and CAF1, and in vitro purified SPT5 specifically could bind to CAF1 and the deadenylase domain of CCR4. We additionally demonstrated that mutations in SPT5 or an spt4 deletion slowed the rate of mRNA degradation, a phenotype associated with defects in the CCR4 mRNA deadenylase complex. Yet, unlike ccr4 and caf1 deletions, spt5 and spt4 defects displayed little effect on the rate of deadenylation. They also did not affect decapping or 5\u27 - 3\u27 degradation of mRNA. These results suggest that the interactions between SPT5/SPT4 and the CCR4-NOT complex are probably the consequences of effects involving nuclear events and do not involve the primary role of CCR4 in mRNA deadenylation and turnover

New estimation and inference procedures for a single-index conditional distribution model

AbstractThis article employs a more flexible single-index regression model to characterize the conditional distribution. The pseudo least integrated squares approach is proposed to estimate the index coefficients. As shown in the numerical results, our estimator outperforms the existing ones in terms of the mean squared error. Moreover, we provide the generalized cross-validation criteria for bandwidth selection and utilize the frequency distributions of weighted bootstrap analogues for the estimation of asymptotic variance and the construction of confidence intervals. With a defined residual process, a test rule is built to check the correctness of an applied single-index conditional distribution model. To tackle the problem of sparse variables, a multi-stage adaptive Lasso algorithm is developed to enhance the ability of identifying significant variables. All of our procedures are found to be easily implemented, numerically stable, and highly adaptive to a variety of data structures. In addition, we assess the finite sample performances of the proposed estimation and inference procedures through extensive simulation experiments. Two empirical examples from the house-price study in Boston and the environmental study in New York are further used to illustrate applications of the methodology