Detection of quantitative trait loci in outbred populations with incomplete marker data

AcrA protein is a component of the multi-drug efflux complex AcrAB-TolC of Escherichia coli. Judged by the hypersusceptibility phenotype of acrA mutants, the AcrAB-TolC system pumps out an extraordinarily wide variety of antibiotics, chemotherapeutic agents, detergents and dyes. This complex traverses both the inner and outer membranes of E. coli and catalyzes efflux of the drugs directly into the medium. The coordinated operation of the inner membrane transporter AcrB and outer membrane channel TolC is thought to be mediated by AcrA. The latter is a lipoprotein located in the periplasmic space. We show here that a lipid-deficient derivative of AcrA is functionally active as demonstrated by the complementation of the hypersusceptibility phenotype of the acrA mutant. Purified non-lipidated and intact forms of AcrA were able to restore, with similar efficiency, the activity of AcrA-dependent efflux of erythromycin in Ca2+-sucrose-treated E. coli cells. Using analytical ultracentrifugation and dynamic light scattering techniques we determined hydrodynamic properties of the non-lipidated AcrA and found that AcrA exists in solution as a highly asymmetric monomeric molecule with an axial ratio of 8. This elongated shape of AcrA is compatible with the hypothesis that this protein spans the periplasmic space coordinating the concerted operation of inner and outer membrane components of the complex.     

Regulatory factors associated with synthesis of the osmolyte glycine betaine in the halophilic methanoarchaeon Methanohalophilus portucalensis

The halophilic methanoarchaeon Methanohalophilus portucalensis can synthesize de novo and accumulate beta-glutamine, Nepsilon-acetyl-beta-lysine, and glycine betaine (betaine) as compatible solutes (osmolytes) when grown at elevated salt concentrations. Both in vivo and in vitro betaine formation assays in this study confirmed previous nuclear magnetic resonance 13C-labelling studies showing that the de novo synthesis of betaine proceeded from glycine, sarcosine, and dimethylglycine to form betaine through threefold methylation. Exogenous sarcosine (1 mM) effectively suppressed the intracellular accumulation of betaine, and a higher level of sarcosine accumulation was accompanied by a lower level of betaine synthesis. Exogenous dimethylglycine has an effect similar to that of betaine addition, which increased the intracellular pool of betaine and suppressed the levels of Nepsilon-acetyl-beta-lysine and beta-glutamine. Both in vivo and in vitro betaine formation assays with glycine as the substrate showed only sarcosine and betaine, but no dimethylglycine. Dimethylglycine was detected only when it was added as a substrate in in vitro assays. A high level of potassium (400 mM and above) was necessary for betaine formation in vitro. Interestingly, no methylamines were detected without the addition of KCl. Also, high levels of NaCl and LiCl (800 mM) favored sarcosine accumulation, while a lower level (400 mM) favored betaine synthesis. The above observations indicate that a high sarcosine level suppressed multiple methylation while dimethylglycine was rapidly converted to betaine. Also, high levels of potassium led to greater amounts of betaine, while lower levels of potassium led to greater amounts of sarcosine. This finding suggests that the intracellular levels of both sarcosine and potassium are associated with the regulation of betaine synthesis in M. portucalensis.     

Auditory continuity and loudness computation

Sequences composed of alternating bursts of different levels with no silences separating them can give rise to a perception of a continuous sound upon which is superimposed an intermittent stream. These experiments sought to determine how the perceived loudness of the intermittent stream depends on the level difference between higher-level and lower-level bursts in the sequence in cases in which continuity is either heard or not heard. In the main experiment, listeners were asked to adjust the level of continuous or intermittent comparison sequences to match the loudness of components that appeared to be either continuous or intermittent in an alternating-level reference sequence, thus urging them to focus on the two-stream percept. Loudness matches of continuous comparison stimulus were close to physical levels of the lower-level bursts, whereas matches of the intermittent comparison stimulus were well below the physical levels of higher-level bursts. These results are discussed in terms of Bregman's [Auditory Scene Analysis (MIT, Cambridge, MA, 1990)] "old-plus-new" hypothesis: The loudness of the intermittent stream should result from the subtraction of the lower level from the higher level under the assumption that the higher-level burst represents a simultaneous mixture of sounds including the continuation of the lower-level burst. Additional experiments verified that, in the absence of the continuity phenomenon, matched levels were very close to the physical levels and that matches to fixed-level continuous and intermittent sequences were precise. The matching results from the main experiment support predictions of neither classical loudness models that do not take auditory organization processes into account nor schema-based models that presume a selection of information from the higher-level burst that does not affect the perceptual content of this burst. The matched levels fell between predictions of models based on subtraction of acoustic pressure and acoustic power, but were very different from subtraction of loudness measured in sones, suggesting that loudness is computed subsequent to auditory organization processes.     

Approximate NMPC for vehicle stability: Design,implementation and SIL testing

In this paper, Nonlinear Model Predictive Control is used to improve vehicle stability and handling by means of a rear active differential. In order to allow on-line control computations within the required sampling time, a Set Membership approximation of the designed controller is employed. The real applicability and effectiveness of such a technique, as well as the improvement over an existing control approach based on Internal Model Control, is shown through the implementation on a commercial embedded device with limited computational capacity and the testing via software-in-the-loop simulations of demanding maneuvers, using an accurate nonlinear vehicle model.     

Pain therapy

NEW OPIOID ANALGESICS: Progress in pain reliet has recently been achieved with the introduction of new opioid analgesics such as tramadol and the pediatric preparation of codeine phosphate as well as powerful long-release opioids which can be administered per os, or percutaneously for transdermal fentanyl. CO-ANALGESICS: Other drugs, mainly antidepressants and anti-convulsants, can be usefully combined with analgesics. New serotonin uptake inhibitors and anticonvulsants (gabapentin and lamotrigin) have the advantage of better tolerance. None of these drugs has marketing approval in France for their pain relieving effects. The same is true for clonidine and neostigmine which, after spinal infusion, potentialize opioids and for ketamine which can relieve neuropathy pain by dissociative anesthesia. NEW ANTI-MIGRAINE DRUGS: New drugs have been developed for specific types of pain such as migraine. The new "triptans" are tolerated better than sumatriptan and is reimbursed by the national social security. REFRACTORY NEUROPATHY PAIN: Indications for electrical stimulation techniques conducted in a neurosurgery unit have been identified. Stimulators may be implanted in spinal or supra-spinal localizations. REGULATORY ASPECTS: New legislation has reorganized health care for pain relief in France. The new texts take into consideration personnel training, the health care network and progress in therapeutics.     

A comparison of hydroxyapatite-coated, titanium-coated, and uncoated tapered external-fixation pins. An in vivo study in sheep

OBJECTIVES: This study focuses on the relevance of size, eloquence, type of venous drainage, the Spetzler-Martin scale as a whole, and other factors, such as rupture of cerebral arteriovenous malformations (AVMs) for the prediction of neurological deficits in the context of microsurgical AVM removal. METHODS: One hundred and fifty patients with AVMs, whose data were retrieved from a prospectively employed computerised data bank were included. Seventeen patients (11.3%) underwent preoperative embolisation. According to the Spetzler-Martin scale they were graded as follows: 22.0% grade I, 32.0% grade II, 29.3% grade III, 14.0% grade IV, and 2.7% grade V. Intracerebral haemorrhage was present in 39.0%. The AVMs were <3 cm in 52.00/0, 3-6 cm in 43.3% and >6 cm in 4.7%; 59.3% of the AVMs were eloquently located and 29.3% had deep venous drainage (DVD). Follow up information was assessed 6 months after surgery in all but one patient, who died. The applied statistical test was chi2. RESULTS: Surgical morbidity was 15.3%. Early new deficits were noted in 39.3%, permanent new deficits in 10.6%, being significant (major) in 7.3%. The occurrence of permanent deficits correlated significantly with size, deep venous drainage, and the Spetzler-Martin scale. There was statistical evidence for a trend in risk of poor surgical outcome across the three categories non-eloquent, "less eloquent" (for example, visual cortex) and "highly eloquent" (brainstem, basal ganglia, or precentral cortex) with the last being associated with the highest risk for permanent neurological compromise. CONCLUSION: "Eloquence" of the Spetzler-Martin scale should be divided into "highly eloquent" and "less eloquent", which is important for risk analysis of the treatment of asymptomatic and deep seated AVMs and for future trials comparing various treatment modalities. In addition, resection of eloquent AVMs v non-eloquent ones is significantly associated with higher surgical morbidity.     

Primary pericardial angiosarcoma with multiple lung and a solitary liver metastases: the clinical and anatomicopathological findings

A case of 66-year-old woman with cardiac tamponade and bilateral pulmonary infiltrates is reported. These infiltrates were "pseudonodulars" and confluent. We practice pericardiocentesis and a hemorrhagic fluid is pulled out. Its cytology shown not neoplastic cells. She died and the necropsy shown an angiosarcoma of pericardium with multiple pulmonary and alone hepatic metastases.     

Value and future of electron beam computed tomography

Mecanic computed tomography would probably never reach the acquisition brevity obtained by EBT. This machine is the best for exploration of cardiovascular diseases, and non cooperative patients, and for cine and flow studies. Morever, there are never tube cooling delays or interruptions in any procedures. Its disadvantages are the price, the impossibility to tilt the gantry, and the computer which are to be improved. With "Evolution", Siemens proposes now improvements with the CVS mode and a computer release without increasing of the price.