Focal dystonia and the Sensory-Motor Integrative Loop for Enacting (SMILE).

Performing accurate movements requires preparation, execution, and monitoring mechanisms. The first two are coded by the motor system, the latter by the sensory system. To provide an adaptive neural basis to overt behaviors, motor and sensory information has to be properly integrated in a reciprocal feedback loop. Abnormalities in this sensory-motor loop are involved in movement disorders such as focal dystonia, a hyperkinetic alteration affecting only a specific body part and characterized by sensory and motor deficits in the absence of basic motor impairments. Despite the fundamental impact of sensory-motor integration mechanisms on daily life, the general principles of healthy and pathological anatomic-functional organization of sensory-motor integration remain to be clarified. Based on the available data from experimental psychology, neurophysiology, and neuroimaging, we propose a bio-computational model of sensory-motor integration: the Sensory-Motor Integrative Loop for Enacting (SMILE). Aiming at direct therapeutic implementations and with the final target of implementing novel intervention protocols for motor rehabilitation, our main goal is to provide the information necessary for further validating the SMILE model. By translating neuroscientific hypotheses into empirical investigations and clinically relevant questions, the prediction based on the SMILE model can be further extended to other pathological conditions characterized by impaired sensory-motor integration.

Comparative gene finding in chicken indicates that we are closing in on the set of multi-exonic widely expressed human genes.

The recent availability of the chicken genome sequence poses the question of whether there are human protein-coding genes conserved in chicken that are currently not included in the human gene catalog. Here, we show, using comparative gene finding followed by experimental verification of exon pairs by RT-PCR, that the addition to the multi-exonic subset of this catalog could be as little as 0.2%, suggesting that we may be closing in on the human gene set. Our protocol, however, has two shortcomings: (i) the bioinformatic screening of the predicted genes, applied to filter out false positives, cannot handle intronless genes; and (ii) the experimental verification could fail to identify expression at a specific developmental time. This highlights the importance of developing methods that could provide a reliable estimate of the number of these two types of genes.

A nucleosome-dependent static loop potentiates estrogen-regulated transcription from the Xenopus vitellogenin B1 promoter in vitro.

We describe the transcriptional potentiation in estrogen responsive transcription extracts of the Xenopus vitellogenin B1 gene promoter through the formation of a positioned nucleosome. Nuclease digestion and hydroxyl radical cleavage indicate that strong, DNA sequence-directed positioning of a nucleosome occurs between -300 and -140 relative to the start site of transcription. Deletion of this DNA sequence abolishes the potentiation of transcription due to nucleosome assembly. The wrapping of DNA around the histone core of the nucleosome positioned between -300 and -140 creates a static loop in which distal estrogen receptor binding sites are brought close to proximal promoter elements. This might facilitate interactions between the trans-acting factors themselves and/or RNA polymerase. Such a nucleosome provides an example of how chromatin structure might have a positive effect on the transcription process.

Matching at one loop for the four-quark operators in NRQCD

The matching coefficients for the four-quark operators in NRQCD (NRQED) are calculated at one loop using dimensional regularization for ultraviolet and infrared divergences. The matching for the electromagnetic current follows easily from our results. Both the unequal and equal mass cases are considered. The role played by the Coulomb infrared singularities is explained in detail.

Loop bifurcation and magnetization rotation in exchange-biased Ni/FeF2

Exchange-biased Ni/FeF2 films have been investigated using vector coil vibrating-sample magnetometry as a function of the cooling field strength HFC . In films with epitaxial FeF2 , a loop bifurcation develops with increasing HFC as it divides into two sub-loops shifted oppositely from zero field by the same amount. The positively biased sub-loop grows in size with HFC until only a single positively shifted loop is found. Throughout this process, the negative and positive (sub)loop shifts maintain the same discrete value. This is in sharp contrast to films with twinned FeF2 where the exchange field gradually changes with increasing HFC . The transverse magnetization shows clear correlations with the longitudinal subloops. Interestingly, over 85% of the Ni reverses its magnetization by rotation, either in one step or through two successive rotations. These results are due to the single-crystal nature of the antiferromagnetic FeF2 , which breaks down into two opposite regions of large domains.

Particle orientation distribution in Y-Fe2O3magnetic tapes by Mössbauer and hysteresis loop measurements

The particle orientation in several Y-Fe2O3magnetic tapes has been quantitatively evaluated by using the data of both Mössbauer and hysteresis loop measurements performed in the three orthogonal directions. A texture function has been obtained as a development of real harmonics. The profile of the texture function gives the quality of the different magnetic tapes. A different degree of particle orientation at the surface of the tape is evidenced by means of conversion electron Mössbauer spectra.

Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.

OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation.

Closing the gap between T-cell life span estimates from stable isotope-labeling studies in mice and humans.

Quantitative knowledge of the turnover of different leukocyte populations is a key to our understanding of immune function in health and disease. Much progress has been made thanks to the introduction of stable isotope labeling, the state-of-the-art technique for in vivo quantification of cellular life spans. Yet, even leukocyte life span estimates on the basis of stable isotope labeling can vary up to 10-fold among laboratories. We investigated whether these differences could be the result of variances in the length of the labeling period among studies. To this end, we performed deuterated water-labeling experiments in mice, in which only the length of label administration was varied. The resulting life span estimates were indeed dependent on the length of the labeling period when the data were analyzed using a commonly used single-exponential model. We show that multiexponential models provide the necessary tool to obtain life span estimates that are independent of the length of the labeling period. Use of a multiexponential model enabled us to reduce the gap between human T-cell life span estimates from 2 previously published labeling studies. This provides an important step toward unambiguous understanding of leukocyte turnover in health and disease.

Analysis of natural variants of the human immunodeficiency virus type 1 gag-pol frameshift stem-loop structure.

Human immunodeficiency virus type 1 uses ribosomal frameshifting for translation of the Gag-Pol polyprotein. Frameshift activities are thought to be tightly regulated. Analysis of gag p1 sequences from 270 plasma virions identified in 64% of the samples the occurrence of polymorphism that could lead to changes in thermodynamic stability of the stem-loop. Expression in Saccharomyces cerevisiae of p1-beta-galactosidase fusion proteins from 10 representative natural stem-loop variants and three laboratory mutant constructs (predicted the thermodynamic stability [Delta G degrees] ranging from -23.0 to -4.3 kcal/mol) identified a reduction in frameshift activity of 13 to 67% compared with constructs with the wild-type stem-loop (Delta G degrees, -23.5 kcal/mol). Viruses carrying stem-loops associated with greater than 60% reductions in frameshift activity presented profound defects in viral replication. In contrast, viruses with stem-loop structures associated with 16 to 42% reductions in frameshift efficiency displayed no significant viral replication deficit.

Etude de la variation interlaboratoire du test de dépistage prénatal des défauts de fermeture du tube neural [Interlaboratory variation in the prenatal screening test for neural tube closing defects].

Early detection of neural-tude defects is possible by determining Alpha-fetoprotein (AFP) in maternal serum. 16'685 pregnant women were observed. Three methods for the determination of the "normal" range are compared. The first one, already used in similar studies, makes use of a constant multiple of the median. The other two ones make use of robust estimates of location and scale. Their comparison shows the interest of the robust methods to reduce the interlaboratory variability.

The contact region between three domains of the extracellular loop of ASIC1a is critical for channel function.

Acid-sensing ion channels are members of the epithelial Na(+) channel/degenerin family. They are neuronal nonvoltage-gated Na(+) channels that are activated by extracellular acidification. In this study, we investigated the role of a highly conserved region of the extracellular part of ASIC1a that forms the contact between the finger domain, the adjacent beta-ball, and the upper palm domain in ASIC1a. The finger domain contributes to the pH-dependent gating and is linked via this contact zone to the rest of the protein. We found that mutation to Cys of residues in this region led to decreased channel expression and current amplitudes. Exposure of the engineered Cys residues to Cd(2+) or to charged methane thiosulfonate sulfhydryl reagents further reduced current amplitudes. This current inhibition was not due to changes in acid-sensing ion channel pH dependence or unitary conductance and was likely due to a decrease of the probability of channel opening. For some mutants, the effect of sulfhydryl reagents depended on the pH of exposure in the range 7.4 to 6.8, suggesting that this zone undergoes conformational changes during inactivation. Our study identifies a region in ASIC1a whose integrity is required for normal channel function.

Examination of Closing the Existing Highway Maintenance Garage at Hamlin, Iowa, 1983

An optimum allocation model has been utilized to examine the existing allocation of highway segments to maintenance garages in the Hamlin study area. The model has also been used to evaluate the financial effect of closing the garage at Hamlin. The examination of the study area shows that only three of 48 highway segments should be reallocated at an annual operational savings of approximately $1,400. The study concludes there would be an annual operational savings of approximately 128,700 if the garage at Hamlin were closed.

An Optimum Allocation Approach to Closing or Relocating Highway Maintenance Garages in Iowa, 1981

Highway maintenance engineers and administrators are often confronted with a number of problems related to highway maintenance work programs. One of these problems is concerned with determining the optimum number and locations of highway maintenance garages in a given area. Serious decline in highway revenues and a high inflation rate have made it necessary to examine existing maintenance practices and to allocate reduced financial resources more effectively and efficiently. Searching for and providing of reasonable solutions to these problems is the focus of this research project. The methodology used is to identify and modify for use (if necessary) those models which have already been developed. Models which could give optimum number and locations of highway maintenance garages were found to be too theoretical and/or practically infeasible. Consequently, research focus was shifted from these models to other models that could compare alternatives and select the best among these alternatives. Three such models -- the Alabama model, California model, and Louisiana model, were identified and studied.

Smith Predictor Sliding Mode Closed-loop Glucose Controller in Type 1 Diabetes

Type 1 diabetic patients depend on external insulin delivery to keep their blood glucose within near-normal ranges. In this work, two robust closed-loop controllers for blood glucose regulation are developed to prevent the life-threatening hypoglycemia, as well as to avoid extended hyperglycemia. The proposed controllers are designed by using the sliding mode control technique in a Smith predictor structure. To improve meal disturbance rejection, a simple feedforward controller is added to inject meal-time insulin bolus. Simulations scenarios were used to test the controllers, and showed the controllers ability to maintain the glucose levels within the safe limits in the presence of errors in measurements, modeling and meal estimation

Generation of symmetric periodic orbits by a heteroclinic loop formed by two singular points and their invariant manifolds of dimension 1 and 2 in R3

In this paper we will find a continuous of periodic orbits passing near infinity for a class of polynomial vector fields in R3. We consider polynomial vector fields that are invariant under a symmetry with respect to a plane and that possess a “generalized heteroclinic loop” formed by two singular points e+ and e− at infinity and their invariant manifolds � and . � is an invariant manifold of dimension 1 formed by an orbit going from e− to e+, � is contained in R3 and is transversal to . is an invariant manifold of dimension 2 at infinity. In fact, is the 2–dimensional sphere at infinity in the Poincar´e compactification minus the singular points e+ and e−. The main tool for proving the existence of such periodic orbits is the construction of a Poincar´e map along the generalized heteroclinic loop together with the symmetry with respect to .