Reduction of disulfide bonds in an amyloidogenic Bence Jones protein leads to formation of "amyloid-like" fibrils in vitro

Motivated by the finding that the amino acid sequence of the Bence Jones protein BJP-DIA was identical to that of the main protein component of the amyloid fibrils obtained from the same patient with AL-amyloidosis, (Klafki, H.-W., Kratzin, H.-D., Pick, A.-I., Eckart, K., Karas, M. & Hilschmann, N. (1992) Biochemistry 31, 3265-3272.), we attempted to create "amyloid-like" fibrils from the Bence Jones protein in vitro, without addition of proteolytic enzymes. Reduction of BJP-DIA, solubilized in PBS, pH 7.4, overnight at 37 degrees C resulted in the formation of a precipitate which had affinity for the dye Congo red. Electron microscopy of negatively stained samples of the reduced protein revealed aggregates of linear unbranched fibrils. SDS-polyacrylamide gel electrophoresis demonstrated that the precipitate consisted almost exclusively of intact light chain molecules. This result makes it possible to deduce a molecular model of these amyloid fibrils generated in vitro.     

Muscle proton T2 relaxation times and work during repetitive maximal voluntary exercise

We studied the effects of progressive maximal voluntary handgrip contractions (MVCs) on muscle proton spin-spin (T2) relaxation times and work, measured as the integrated force vs. time curve (FTI). Six healthy volunteers performed 10, 20, 40, and 80 MVCs in a 0.35-T magnet on four separate occasions. Repeated measures analyses of variance of increases in T2 and FTI during successive bouts were significant (P < 0.005 and P < 0.001, respectively). FTI increased with successive bouts to a greater extent than did muscle T2 (P < 0.05). For T2, the Helmert contrast judged the 10-MVC response lower than the mean of the remaining responses (P < 0.005), and the differences between all others compared with the means of subsequent responses were not significant, indicating a "flattening" of the T2 response after the increase from 10 to 20 repetitions. For FTI, all the single degree of freedom Helmert contrasts were significant (P < 0.001), indicating a continual increase in response over increased MVCs. The curved nature of the T2 response conformed best to a hyperbolic function, suggesting that a limit of approximately 32% exists for the change in T2 during progressively longer bouts of MVCs. A limit in the T2 response is consistent with the existence of a limit in the amount of water that muscle can take up from the vasculature during exertion.     

Inhibition of HeLa cell messenger RNA translation by 7-methylguanosine 5'-monophosphate

Translation of HeLa cell RNA containing poly(A) in a wheat germ cell-free system is markedly but incompletely inhibited by 7-methylguanosine 5'-monophosphate (m7G5'p). We have analyzed the translation products synthesized in the presence of different concentrations of m7G5'p and find that translation of all mRNAs is equally inhibited. To demonstrate the specificity of the inhibitor for RNAs with 5'-terminal m7G5' ppp... we show that specific translation products of satellite tobacco necrosis virus RNA, which does not have this 5' terminus, are synthesized in the presence of m7G5' p. Protein synthesis programmed by endogenous mRNA in a HeLa cell-free system is inhibited after a 10-min lag by m7G5' p. Other guanosine nucleotides without the 7-methyl group or with the phosphate in a different position are not inhibitor. We show that translation of all mRNAs is inhibited to a similar extent by m7G5'p in the HeLa cell-free system, by synthesizing 35S-labeled proteins in the presence of different inhibitory concentrations of this nucleotide and analyzing the translation products by electrophoresis and autoradiography. Translation of encephalomyocarditis virus RNA added to the HeLa cell-free system is not inhibited by m7"g5p; this viral RNA does not have this nucleotide at the 5' terminus. This indicates that m7G5'p specifically inhibits translation of mRNAs with the 5' terminus m7G5'ppp... and suggests that initiation of translation of picornavirus RNA may proceed via a mechanism different from that of cellular mRNAs.     

Relationship of passive cigarette-smoking to sudden infant death syndrome

The smoking habits of 56 families who lost babies to the sudden infant death syndrome (SIDS) were compared to those of 86 control families. A higher proportion of SIDS mothers smoked both during pregnancy (61% vs. 42%) and after their babies were born (59% vs. 37%). SIDS mother also smoked a significantly greater number of cigarettes than controls. Exposure to cigarette smoke ("passive smoking") appears to enhance the risk of SIDS for reasons not known.     

The effect of epidural anesthesia on uterine activity and blood pressure

Because of the unresolved controversy regarding the effect of epidural anesthesia upon uterine contractility, it was decided to study its effect on a small number of patients. Intrauterine and intra-arterial continuous pressure, continuous fetal heart rate, and maternal heart rate recordings were obtained from at least 20 minutes before administration of the epidural anesthic until complete dilatation in these patients. Nineteen patients were in spontaneous labor, and 18 had labor stimulated with oxytocin. Plain lidocaine, 1 or 1.5%, was used in 12 patients (30 observations), and lidocaine with epinephrine, 1:200,000 was used in 26 patients (51 observations). Uterine contractions were calculated in Montevideo units for 60 minutes following the epidural anesthetic. The changes, if any, were compared in both groups. There was a significant decrease in uterine activity when epinephrine was added to the anesthetic solution, mainly a lessening of intensity. There were comparable decreases in systolic/diastolic blood pressure in both groups and compensatory tachycardia. In one case, severe hypertension was observed following administration of lidocaine epinephrine. It was concluded that the addition of epinephrine to the anesthetic solution predictably produces diminution of uterine activity, and it does not give "cardiovascular support" to the laboring patient.     

Determination of fibrin and fibrinogen split products by their anticoagulant activity

A new diagnostic method to determine fibrinogen and fibrin splitting products is based on the fact that high-molecular fragments acting as specific inhibitors of fibrin self-assembly compose these products. Fibrinogen and fibrin splitting products are detected and determined quantitatively by prolongation of coagulation time in the test with the standard monomeric fibrin. The number of units of anticoagulating activity in the studied urine are the results of the determinations. Sensitivity of the method if necessary may be increased by adding of a certain amount of the fibrinogen and fibrin splitting products to the test that makes a favourable background for the action of the products. The method is rather sensitive, reliable and simple. It may be used in ordinary clinical laboratories. The method proved to be quite satisfactory when testing renal diseases at the clinic. It is of great significance for early detection of the transplanted kidney rejection. The new method is compared with the known immunological method which consist in determination of the inhibitory effect of the fibrinogen and fibrin splitting products on agglutination of erythrocytes of specific antibodies; the erythrocytes being subjected to "tanning" and "loading" with fibrinogen. A satisfactory correlation is found between the results of two methods.     

Data‐driven bounded‐error fault detection

In this paper, a new data‐driven fault‐detection method is proposed. This method is based on a new nonparametric system identification approach, which constitutes the principal contribution to this work. The fault‐detection method is a parametric model‐free approach that can be applied to nonlinear systems that work at various operating points. Not only can the fault‐detection process be applied to the steady state of each operating point, but it can also be applied to the transient state resulting from a change in the operating point. In order to detect faults, the proposed method uses an interval predictor based on bounded‐error techniques. The utilization of techniques based on bounded error enables system uncertainties to be included in an explicit way. This in turn leads to the possibility of obtaining interval predictions of the behaviour of the system, which include information on the reliability of the prediction itself. In order to show the effectiveness of the fault‐detection method, two examples are presented: in the form of a simulated process (counter‐flow shell‐and‐tube heat‐exchanger system) and an example of a real application (two‐tanks system). A comparison with two fault‐detection methods has also been included. Copyright © 2013 John Wiley & Sons, Ltd.     

Stability analysis of PWM feedback control systems with PID regulators

Stability analysis is of great significance in those feedback control systems in which the power amplifier is operated as a pulse-modulator device, since under these circumstances the whole control system is highly non-linear. Stability in PWM feedback control systems with a proportional type regulator has been amply described in the literature. Only recently, however, have such studies been extended to include systems with a proportional-plus-integral regulator. In this paper the problem is considered for the case involving a PWM control system, where the regulator is a proportional-plus-integral-plus-derivative, the PWM modulator is of a very general type and the controlled process is of arbitrary order. The stability of the system is analysed by means of a discrete version of the second Lyapunov method ; this method in turn leads to an investigation of the positivity region of a quadratic form defined in the parameter space of the regulator. To improve the stability region obtained, a procedure is investigated whereby only a few parameters of the quadratic Lyapunov function need to be varied. The method proposed has proved extremely simple and flexible to apply, even in cases where the system is of arbitrary order.     

The Dirac Equation in the Kerr-de Sitter Metric

We consider a Fermion in the presence of a rotating BH immersed in a universe with a positive cosmological constant. After presenting a rigorous classification of the number and type of the horizons, we adopt the Carter tetrad to separate the aforementioned equation into radial and angular equations. We show how the Chandrasekhar ansatz leads to the construction of a symmetry operator that in the limit of a vanishing cosmological constant reproduces the square root of the squared total angular momentum operator for a Dirac particle in the Kerr metric. Furthermore, we prove that the the spectrum of the angular operator is discrete and consists of simple eigenvalues, and by means of the functional Bethe ansatz method we also derive a set of necessary and sufficient conditions for the angular operator to have polynomial solutions. Finally, we show that there exist no bound states for the Dirac equation in the non-extreme case.