Folate receptors targeted to clathrin-coated pits cannot regulate vitamin uptake.

Potocytosis is an endocytic process that is specialized for the internalization of small molecules. Recent studies on the uptake of 5-methyltetrahydrofolate by the folate receptor have suggested that the glycosyl-phosphatidylinositol anchor on this protein causes it to cluster and be internalized by caveolae instead of coated pits. To test this hypothesis directly, we have constructed a chimeric folate receptor that has the glycosyl-phosphatidylinositol anchor replaced with the transmembrane domain and cytoplasmic tail of the low density lipoprotein receptor. The cells with wild-type receptors delivered 5-methyltetrahydrofolate to the cytoplasm more rapidly than did cells expressing the chimeric receptor. This suggests that efficient delivery to the cytoplasm depends on caveolae. In sharp contrast to cells with wild-type folate receptors, cells internalizing folate by clathrin-coated pits were unable to decrease vitamin uptake when they were either folate replete or confluent.

Abnormal junctions between surface membrane and sarcoplasmic reticulum in skeletal muscle with a mutation targeted to the ryanodine receptor.

Junctions that mediate excitation-contraction (e-c) coupling are formed between the sarcoplasmic reticulum (SR) and either the surface membrane or the transverse (T) tubules in normal skeletal muscle. Two structural components of the junctions, the feet of the SR and the tetrads of T tubules, have been identified respectively as ryanodine receptors (RyRs, or SR calcium-release channels), and as groups of four dihydropyridine receptors (DHPRs, or voltage sensors of e-c coupling). A targeted mutation (skrrm1) of the gene for skeletal muscle RyRs in mice results in the absence of e-c coupling in homozygous offspring of transgenic parents. The mutant gene is expected to produce no functional RyRs, and we have named the mutant mice "dyspedic" because they lack feet--the cytoplasmic domain of RyRs anchored in the SR membrane. We have examined the development of junctions in skeletal muscle fibers from normal and dyspedic embryos. Surprisingly, despite the absence of RyRs, junctions are formed in dyspedic myotubes, but the junctional gap between the SR and T tubule is narrow, presumably because the feet are missing. Tetrads are also absent from these junctions. The results confirm the identity of RyRs and feet and a major role for RyRs and tetrads in e-c coupling. Since junctions form in the absence of feet and tetrads, coupling of SR to surface membrane and T tubules appears to be mediated by additional proteins, distinct from either RyRs or DHPRs.

Employee Motivation: Effective Incentives Targeted at Keeping the Baby Boomers in the Workplace beyond Normal Retirement Age

The impending mass retirement of the Baby Boom generation in the United States may cause a drastic talent drain. Companies should pay attention to this upcoming problem now to alleviate an exodus by encouraging Baby Boomers to continue working past their normal retirement age. One solution is to offer them effective incentives. The most compelling incentives for Baby Boomers are the ability to choose their own hours (how many hours they wish to work, and when they wish to work them), the ability to telecommute from wherever they choose, and the offer of extra health care benefits.

The EU's Use of 'Targeted' Sanctions: Evaluating effectiveness. CEPS Working Document No. 391, March 2014

This study analyses the use by the European Union of the novel concept of ‘targeted sanctions’ in the framework of its Common Foreign and Security Policy. It examines two sets of sanctions regimes featuring different degrees of efficacy: in Myanmar and Zimbabwe, the EU wielded measures in support of human rights and democracy objectives in the absence of a United Nations mandate, while it supplemented UN sanctions to stop nuclear proliferation in Iran and North Korea. The study highlights a number of facilitators of, or hindrances to, the efficacy of sanctions, such as the degree of support by regional powers or the presence of UN legitimation. It concludes that the EU sanctions regimes could be optimised by using more robust measures, designing them on the basis of ex ante assessments, enabling faster upgrades, monitoring their impact and adjusting them regularly and improving outreach efforts.

How did Targeted Government Trade Policies Impact the Productivity of Manufacturing Firms in Eastern Europe and Central Asia between 1995 and 2009? ACES Working Papers, 28 August 2012

This study investigates whether trade-related, targeted, government policies had an impact on the total factor productivity (TFP) of manufacturing firms in Eastern Europe and Central Asia (ECA region) between 1995 and 2009. It does so by looking at how different types of primarily industry-specific trade policies (or their combinations) impacted firm productivity. The dependent variable is firm total factor productivity (TFP), calculated using the Levinsohn-Petrin approach. As an alternative measure of firm productivity, this study uses labor productivity. This study finds that, in most instances (10 out of 14 times), targeted policies do not show a significant impact on manufacturing firms’ TFP. Based on the analysis of 588 manufacturing firms in the ECA region, this study finds that, contrary to proponents of targeted policies, targeted trade-related government policies have a limited impact on the total factor productivity (TFP) in developing countries.

Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

The impact of the targeted harmonized wage code on unemployment insurance /

"May 2002"--Prelim. p.

Modern therapeutics, medical and surgical; including the diseases of women and children. A compendium of recent formulae and therapeutical directions from the practice of eminent contemporary physicians, American and foreign.

Combined ed. of his Modern medical therapeutics, Modern surgical therapeutics, Therapeutics of gynecology and Obstetrics, and Therapeutics of diseases of children.

Targeted Jobs Tax Credit (TJTC) Program.

Shipping list no.: 88-549-P.

Elements of materia medica and therapeutics : including the recent discoveries and analysis of medicines /

Fecha sacada del prólogo de la 3a. edición.

Elements of electro-biology, or the voltaic mechanism of man of electro-pathology, especially of the nervous system and of electro-therapeutics /

Mode of access: Internet.

Lectures on materia medica and therapeutics, delivered in the College of Physicians and Surgeons of the University of the State of New York /

Mode of access: Internet.

Elements of materia medica and therapeutics : including the recent discoveries and analyses of medicines /

Mode of access: Internet.