Signal set design with constrained amplitude spectrum and specifiedtime-bandwidth product

A new method for designing signals with a given time-bandwidth product, such that all the signals in the set have a flat amplitude spectrum and have low cross-correlation function values is introduced. It is shown that these signals lie on a signal parameter space ellipse. For a given duration and bandwidth, it is possible to trade off the cardinality of the set for better cross-correlation properties between remaining members of the set. Proof that the cross-correlation between these signals is bounded from above by a factor proportional to the square-root of inverse distance between these signals along one of the axes of the ellipse is given. It is also shown that the cross-correlation between two signals that are furthest apart is bounded by the square-root of inverse time-bandwidth product of the signals in the set. An example design is then given and a comparison of this signal set to some well-known signal sets illustrates that it performs better when the metric is maximum cross-correlation value. The proposed signal set also has the advantage that it can be designed for any time-bandwidth product instead of discrete values     

The synapse-associated protein rapsyn regulates tyrosine phosphorylation of proteins colocalized at nicotinic acetylcholine receptor clusters

Protein tyrosine phosphorylation has been suggested to play an important role in the clustering of the nicotinic acetylcholine receptor (AChR) at the developing neuromuscular junction. Recent studies have shown that the 43-kDa synapse-associated protein rapsyn induces clustering of the AChR in heterologous expression systems. In this study we examined whether tyrosine phosphorylation is involved in this rapsyn-induced AChR clustering. Rapsyn-induced AChR clusters in fibroblasts contain phosphotyrosine, as detected using immunofluorescent labeling with anti-phosphotyrosine antibodies. No anti-phosphotyrosine staining of rapsyn clusters is seen in the absence of AChR expression, indicating that the AChR is required for the appearance of phosphotyrosine at clusters. In addition, coexpression of rapsyn with the AChR induces the tyrosine phosphorylation of the beta amd delta subunits of the AChR. Surprisingly, mutation of the tyrosine phosphorylation sites in the AChR did not inhibit rapsyn-induced clustering of the AChR and clusters of the mutant AChRs still contained high levels of phosphotyrosine. Experiments with single AChR subunits demonstrate that the alpha subunit of the AChR appears to be necessary and sufficient for codistribution of phosphotyrosine with rapsyn-induced clusters of AChR subunits. Finally, transfection of cells with rapsyn activates cellular protein tyrosine kinase activity, resulting in the tyrosine phosphorylation of several membrane-associated proteins. These results suggest that rapsyn may therefore regulate clustering at least in part by regulating the tyrosine phosphorylation of cellular proteins.     

Off-label dermatologic therapies. Usage, risks, and mechanisms

Off-label refers to the prescribing of Food and Drug Administration-approved drugs for a use not indicated on the package insert. The prescribing of off-label drugs may benefit patients with many dermatologic diseases including angiogenesis-related conditions. We surveyed 55 dermatologists from a single large academic program to assess their use of particular drugs for specific skin conditions, their perception of such use as being for Food and Drug Administration-approved or for off-label indications, and their attitudes towards off-label therapies. The practice of prescribing off-label drugs was common among the respondents, many of whom had misperceptions about which conditions are Food and Drug Administration-approved indications and about the legal ramifications of off-label therapies. We suggest that understanding the principles of off-label prescribing in conjunction with the mechanisms of drug action in diseases may help clinicians exercise their judgment in finding innovative therapies for their patients.     

Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups

BACKGROUND: Exercise testing is useful in the assessment of symptomatic patients for diagnosis of significant or extensive coronary disease and to predict their future risk of cardiac events. The Duke treadmill score (DTS) is a composite index that was designed to provide survival estimates based on results from the exercise test, including ST-segment depression, chest pain, and exercise duration. However, its usefulness for providing diagnostic estimates has yet to be determined. METHODS AND RESULTS: A logistic regression model was used to predict significant (>/=75% stenosis) and severe (3-vessel or left main) coronary artery disease, and a Cox regression analysis was used to predict cardiac survival. After adjustment for baseline clinical risk, the DTS was effectively diagnostic for significant (P<0.0001) and severe (P<0.0001) coronary artery disease. For low-risk patients (score >/=+5), 60% had no coronary stenosis >/=75% and 16% had single-vessel >/=75% stenosis. By comparison, 74% of high-risk patients (score <-11) had 3-vessel or left main coronary disease. Five-year mortality was 3%, 10%, and 35% for low-, moderate-, and high-risk DTS groups (P<0.0001). CONCLUSIONS: The composite DTS provides accurate diagnostic and prognostic information for the evaluation of symptomatic patients evaluated for clinically suspected ischemic heart disease.     

Enhanced post-receptor insulin effects in women following dehydroepiandrosterone infusion

While treatment for the neonate continues to be challenging, current technical advances offer more options. Before the 1980s chronic dialysis was technically so difficult for neonates and infants that most considered it impossible; in the 1990s renal replacement therapy is a viable choice. The purpose of this article is neither to advocate active intervention nor passive supportive care, but to help the reader consider questions frequently faced when deciding what to do for a neonate with end-stage renal disease (ESRD). Today ethical issues are tied closely to health care reform, so this bioethical dilemma has only begun. As health care reform addresses benefits of care, the bioethical dilemmas raised by neonates with ESRD will need to carefully considered.     

Identification of mRNA, localized at various segments of the Xenopus laevis embryo at early stages of the gastrula

METHODS: In a randomized double-blind study, 134 patients were given 500 mg metronidazole as an intravenous infusion immediately before operation for abdominal total hysterectomy and again 8 hours later and 124 patients received placebo. RESULTS: There was more wound infection, postoperative hospitalization was longer and the sedimentation rate on the sixth postoperative day was significantly higher in the placebo group. There was no difference in postoperative temperature. Postoperative wound infections occurred in 12% in the placebo group and 6% in the metronidazole group. Eight percent in the total material had urinary tract infections, the diagnosis was based on urine cultures. CONCLUSIONS: Prophylaxis with intravenous infusion of metronidazole is recommended in total hysterectomies.     

Sarcoidosis with nasal obstruction and septal perforation

Although sarcoidosis is predominantly a pulmonary disorder, it often produces disease in the head and neck. For this reason, otolaryngologists should be comfortable in evaluating and treating the disease. The diagnosis of sarcoidosis often can be made with a biopsy of conjunctival or oral mucosa, even when disease manifestations are not apparent in those parts of the body. In a case of sarcoidosis involving the nose, a 54-year-old black man had a proliferation of small lumps on the tip of his nose. For many years, he had had daily epistaxis, anosmia and severe difficulty breathing through this nose. The bridge of his nose was deformed, and he had a large anterior septal perforation. Physical examination revealed palpable bilateral cervical lymphadenopathy. Laboratory test results were, for the most part, normal; however, fine-needle aspiration of one of the cervical lymph nodes showed multiple epithelioid granulomas with interspersed lymphocyte, and an incisional biopsy of the nasal tissue was highly suggestive of sarcoidosis. Unenhanced computed tomography also revealed widespread nasal inflammation and an abnormal soft tissue mass anterior to the maxilla consistent with chronic osteomyelitis. The patient's condition dramatically improved following treatment with oral prednisone; however, he considered undergoing reconstructive surgery for the noticeable nasal septal deformity.     

Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene

The gastrointestinal hormone, glucagon-like peptide-1(7-36)amide (GLP-1) is released after a meal. The potency of synthetic GLP-1 in stimulating insulin secretion and in inhibiting glucagon secretion indicates the putative physiological function of GLP-1. In vitro, the nonmammalian peptide, exendin(9-39)amide [ex(9-39)NH2], is a specific and competitive antagonist of GLP-1. This in vivo study examined the efficacy of ex(9-39)NH2 as an antagonist of exogenous GLP-1 and the physiological role of endogenous GLP-1. Six healthy volunteers underwent 10 experiments in random order. In each experiment, a 30-min period of euglycemia was followed by an intravenous infusion of glucose for 150 min that established a stable hyperglycemia of 8 mmol/liter. There was a concomitant intravenous infusion of one of the following: (1) saline, (2) GLP-1 (for 60 min at 0.3 pmol . kg-1 . min-1 that established physiological postprandial plasma levels, and for another 60 min at 0.9 pmol . kg-1 . min-1 to induce supraphysiological plasma levels), (3-5) ex(9-39)NH2 at 30, 60, or 300 pmol . kg-1 . min-1 + GLP-1, (6-8) ex(9-39)NH2 at 30, 60, or 300 pmol . kg-1 . min-1 + saline, (9 and 10) GIP (glucose-dependent insulinotropic peptide; for 60 min at 0.8 pmol . kg-1 . min-1, with saline or ex(9-39)NH2 at 300 pmol . kg-1 . min-1). Each volunteer received each of these concomitant infusions on separate days. ex(9-39)NH2 dose-dependently reduced the insulinotropic action of GLP-1 with the inhibitory effect declining with increasing doses of GLP-1. ex(9-39)NH2 at 300 pmol . kg-1 . min-1 blocked the insulinotropic effect of physiological doses of GLP-1 and completely antagonized the glucagonostatic effect at both doses of GLP-1. Given alone, this load of ex(9-39)NH2 increased plasma glucagon levels during euglycemia and hyperglycemia. It had no effect on plasma levels of insulin during euglycemia but decreased plasma insulin during hyperglycemia. ex(9-39)NH2 did not alter GIP-stimulated insulin secretion. These data indicate that in humans, ex(9-39)NH2 is a potent GLP-1 antagonist without any agonistic properties. The pancreatic A cell is under a tonic inhibitory control of GLP-1. At hyperglycemia, the B cell is under a tonic stimulatory control of GLP-1.