Indirect Targeting Research Articles

Neurophysiological refinement of subthalamic nucleus targeting.

Advances in image-guided stereotactic surgery, microelectrode recording techniques, and stimulation technology have been the driving forces behind a resurgence in the use of functional neurosurgery for the treatment of movement disorders. Despite the dramatic effects of deep brain stimulation (DBS) techniques in ameliorating the symptoms of Parkinson's disease, many critical questions related to the targeting, effects, and mechanisms of action of DBS remain unanswered. In this report, we describe the methods used to localize the subthalamic nucleus (STN) and we present the characteristics of encountered cells. Twenty-six patients with idiopathic Parkinson's disease underwent simultaneous, bilateral, microelectrode-refined, DBS electrode implantation into the STN. Direct and indirect magnetic resonance imaging-based anatomic targeting was used. Cellular activity was analyzed for various neurophysiological parameters, including firing rates and interspike intervals. Physiological targeting confirmation was obtained by performing macrostimulation through the final DBS electrode. The average microelectrode recording time for each trajectory was 20 minutes, with a mean of 5.2 trajectories/patient. Typical trajectories passed through the anterior thalamus, zona incerta/fields of Forel, STN, and substantia nigra-pars reticulata. Each structure exhibited a characteristic firing pattern. In particular, recordings from the STN exhibited an increase in background activity and an irregular firing pattern, with a mean rate of 47 Hz. The mean cell density was 5.6 cells/mm, with an average maximal trajectory length of 5.3 mm. Macrostimulation via the DBS electrode yielded mean sensory and motor thresholds of 4.2 and 5.7 V, respectively. The principal objectives of microelectrode recording refinement of anatomic targeting are precise identification of the borders of the STN and thus determination of its maximal length. Microelectrode recording also allows identification of the longest and most lateral segment of the STN, which is our preferred target for STN DBS electrode implantation. Macrostimulation via the final DBS electrode is then used primarily to establish the side effect profile for postoperative stimulation. Microelectrode recording is a helpful targeting adjunct that will continue to facilitate our understanding of basal ganglion physiological features.

Utilization of the indirect lysosome targeting pathway by lysosome-associated membrane proteins (LAMPs) is influenced largely by the C-terminal residue of their GYXXphi targeting signals.

A systematic study was conducted on the requirements at the C-terminal position for the targeting of LAMPs to lysosomes, examining the hypothesis that a bulky hydrophobic residue is required. Mutations deleting or replacing the C-terminal valine with G, A, C, L, I, M, K, F, Y, or W were constructed in a reporter protein consisting of the lumenal/extracellular domain of avian LAMP-1 fused to the transmembrane and cytoplasmic domains of LAMP-2b. The steady-state distribution of each mutant form in mouse L-cells was assessed by quantitative antibody binding assays and immunofluorescence microscopy; efficiency of internalization from the plasma membrane and delivery to the lysosome were also estimated. It is found that (a) only C-terminal V, L, I, M, and F mediated efficient targeting to lysosomes, demonstrating the importance hydrophobicity and an optimal size of the C-terminal residue in targeting; (b) efficiency of lysosomal targeting generally correlated with efficiency of internalization; and (c) mutant forms that did not target well to lysosomes showed unique distributions in cells rather than simply default accumulation in the plasma membrane. Interactions of the targeting signals with adaptor subunits were measured using a yeast two-hybrid assay. The results are consistent with the hypothesis that trafficking of LAMP forms in cells through the indirect pathway is determined by the affinities of their targeting signals, predominantly for the mu2 and mu3 adaptors involved at plasma membrane and endosomal cellular sorting sites, respectively.

Mis-Targeting by the Grameen Bank: A Possible Explanation

summary There has been an increased emphasis on the targeting efficiency of micro‐credit programmes. In general, recent studies find a much higher incidence of mis‐targeting (around 25‐30 per cent) than previous studies (3‐5 per cent). Household survey data from four villages in Madhupur Thana is used to test the hypothesis that rapid progressive lending in the study area since 1992 has affected the selection and participation incentives and worsened both the incidence and severity of mis‐targeting. The implication of this finding, if found to hold across other settings, is that loan size and the pace of progressive lending can be used as an indirect targeting instrument. In broader terms, experiments with contract design and service diversification could be useful in covering and benefiting a broader spectrum of the poor.

Identifying the poor for efficient targeting: Results for papua new guinea

Many countries try to protect their poor during structural adjustment. Targeting is needed to prevent benefits leaking to the non‐poor but screening for direct transfers may be too costly for developing countries. One solution is indirect targeting, based on the characteristics of the poor. Household survey data for urban areas of Papua New Guinea are used to show how a poverty index and probit estimation can identify multiple characteristics of poor households. The results suggest that interventions should be targeted towards larger households, where the head is unemployed and has lower levels of schooling. Female headship and age are not useful characteristics for targeting.

Model systems for intestinal lymphatic transport studies.

Transport via the intestinal lymphatic system has been shown to contribute to the absorption of a number of highly lipophilic xenobiotics (Yeung and von Saigent, 1972; Noguchi et al., 1985; Fukui et al., 1989; Ichihashi et al., 1991a). Although intestinal lymphatic drug transport leads directly to an increase in oral bioavailability, it also confers other potential advantages such as avoidance of hepatic first-pass metabolism, direct targeting to the associated lymphoid tissue, and indirect targeting to specific sites such as those associated with low-density lipoprotein receptors and lymphocytes (Bijsterbosch and van Berkel, 1990; Charman and Stella, 1991).

Interest rates and the conduct of monetary policy

The paper describes actual Federal Reserve interest-rate targeting procedures and addresses a number of issues in light of these stylized facts. It reviews the connection between rate smoothing and price level trend-stationarity. It critiques interest-rate targeting as inflation tax smoothing. It argues that stabilization policy implemented by interest-rate targeting may inadvertently induce martingale-like behavior in nominal rates and inflation. The paper explains why central bankers prefere continuity of the short rate and indirect rate targeting. Lastly, it surveys empirical evidence of the Fed's influence over short-term interest rates. (JEL: 311)

Interest Rates and the Conduct of Monetary Policy

The paper describes key aspects of actual Federal Reserve interest rate targeting procedures and addresses a number of issues in light of these stylized facts. It reviews the connection between rate smoothing and price level trend-stationarity. It critiques interest rate targeting as inflation tax smoothing. It argues that stabilization policy implemented by interest rate targeting may inadvertently induce martingale-like behavior in nominal rates and inflation. The paper explains why central bankers prefer continuity of the short rate and indirect rate targeting. Lastly, it surveys empirical evidence of the Fed's influence over short-term interest rates.

News

Rab GTPases constitute the largest family of small GTPases. Rabs regulate not only membrane trafficking but also cell signaling, growth and survival, and development. Increasingly, Rabs and their effectors are shown to be overexpressed or subject to loss-of-function mutations in a variety of disease settings, including cancer progression. This review provides an overview of dysregulated Rab proteins in cancer, and highlights the signaling and secretory pathways in which they operate, with the aim of identifying potential avenues for therapeutic intervention. Recent progress and perspectives for direct and/or indirect targeting of Rabs are also summarized.