Reach task-associated excitatory overdrive of motor cortical neurons following infusion with ALS-CSF

Converging evidence from transgenic animal models of amyotrophic lateral sclerosis (ALS) and human studies suggest alterations in excitability of the motor neurons in ALS. Specifically, in studies on human subjects with ALS the motor cortex was reported to be hyperexcitable. The present study was designed to test the hypothesis that infusion of cerebrospinal fluid from patients with sporadic ALS (ALS-CSF) into the rat brain ventricle can induce hyperexcitability and structural changes in the motor cortex leading to motor dysfunction. A robust model of sporadic ALS was developed experimentally by infusing ALS-CSF into the rat ventricle. The effects of ALS-CSF at the single neuron level were examined by recording extracellular single unit activity from the motor cortex while rats were performing a reach to grasp task. We observed an increase in the firing rate of the neurons of the motor cortex in rats infused with ALS-CSF compared to control groups. This was associated with impairment in a specific component of reach with alterations in the morphological characteristics of the motor cortex. It is likely that the increased cortical excitability observed in the present study could be the result of changes in the intrinsic properties of motor cortical neurons, a dysfunctional inhibitory mechanism and/or an underlying structural change culminating in a behavioral deficit.

A water model study of the flow asymmetry inside a continuous slab casting mold

The work studies the extent of asymmetric flow in water models of continuous casting molds of two different configurations. In the molds where fluid is discharged through multiple holes at the bottom, the flow pattern in the lower portion depends on the size of the lower two recirculating domains. If they reach the mold bottom, the flow pattern in the lower portion is symmetrical about the central plane; otherwise, it is asymmetrical. On the other hand, in the molds where the fluid is discharged through the entire mold cross section, the flow pattern is always asymmetrical if the aspect ratio is 1:6.25 or more. The fluid jet swirls while emerging through the nozzle. The interaction of the swirling Jets with the wide sidewalls of the mold gives rise to asymmetrical flow inside the mold. In the molds with lower aspect ratios, where the jets do not touch the wide side walls, the flow pattern is symmetrical about the central plane.

Bridged systems via radical cyclization reactions. Stereospecific synthesis of chiral tricyclo[6.2.1.0(1,5)]undecanes

The application of radical-mediated cyclizations and annulations in organic synthesis has grown in importance steadily over the years to reach the present status where they are now routinely used in the strategy-level planning.2 The presence of a quaternary carbon atom is frequently encountered in terpenoid natural products, and it often creates a synthetic challenge when two or more quaternary carbon atoms are present in a contiguous manner.3 Even though creation of a quaternary carbon atom by employing a tertiary radical is very facile, creation of a quaternary carbon atom (or a spiro carbon atom) via radical addition onto a fully substituted olefinic carbon atom is not that common but of synthetic importance. For example, the primary radical derived from the bromide 1 failed to cyclize to generate the two vicinal quaternary carbon atoms and resulted in only the reduced product 2.4 The tricyclic carbon framework tricyclo[6.2.1.01,5]undecane (3) is present in a number of sesquiterpenoids e.g. zizzanes, prelacinanes, etc.5

Analytical solution of unsteady three-dimensional MHD boundary layer flow and heat transfer due to impulsively stretched plane surface

The unsteady magnetohydrodynamic viscous flow and heat transfer of Newtonian fluids induced by an impulsively stretched plane surface in two lateral directions are studied by using an analytic technique, namely, the homotopy method. The analytic series solution presented here is highly accurate and uniformly valid for all time in the entire region. The effects of the stretching ratio and the magnetic field on the surface shear stresses and heat transfer are studied. The surface shear stresses in x- and y-directions and the surface heat transfer are enchanced by increasing stretching ratio for a fixed value of the magnetic parameter. For a fixed stretching ratio, the surface shear stresses increase with the magnetic parameter, but the heat transfer decreases. The Nusselt number takes longer time to reach the steady state than the skin friction coefficients. There is a smooth transition from the initial unsteady state to the steady state.

Unsteady Natural Convection Flow in a Square Cavity Filled with a Porous Medium Due to Impulsive Change in Wall Temperature

Unsteady natural convection flow in a two- dimensional square cavity filled with a porous material has been studied. The flow is initially steady where the left- hand vertical wall has temperature T-h and the right- hand vertical wall is maintained at temperature T-c ( T-h > T-c) and the horizontal walls are insulated. At time t > 0, the left- hand vertical wall temperature is suddenly raised to (T-h) over bar ((T-h) over bar > T-h) which introduces unsteadiness in the flow field. The partial differential equations governing the unsteady natural convection flow have been solved numerically using a finite control volume method. The computation has been carried out until the final steady state is reached. It is found that the average Nusselt number attains a minimum during the transient period and that the time required to reach the final steady state is longer for low Rayleigh number and shorter for high Rayleigh number.

Theoretical-Studies on the Modes of Binding of Some of the Beta-Glycosidically Linked Glucobioses to Concanavalin-A

The probable modes of binding for methyl-α-d-sophoroside, methyl-β-d-sophoroside, laminariboise and cellobiose to concanavalin A have been determined using theoretical methods. Methyl-d-sophorosides can bind to concanavalin A in two modes, i.e. by placing their reducing as well as non-reducing sugar units in the carbohydrate specific binding site, whereas laminaribiose and cellobiose can reach the binding site only with their non-reducing glucose units. However, the probability for methyl-α-d-sophoroside to bind to concanavalin A with its reducing sugar residue as the occupant of the binding site is much higher than it is with its non-reducing sugar residue as the occupant of the sugar binding site. A few of the probable conformers of methyl-β-d-sophoroside can bind to concanavalin A with either the reducing or non-reducing glucose unit. Higher energy conformers of cellobiose or laminaribiose can reach the binding site with their non-reducing residues alone. The relative differences in the binding affinities of these disaccharides are mainly due to the differences in the availability of proper conformers which can reach the binding site and to non-covalent interactions between the sugar and the protein. This study also suggests that though the sugar binding site of concanavalin A accommodates a single sugar residue, the residue outwards from the binding site also interacts with concanavalin A, indicating the existence of extended concanavalin A carbohydrate interactions.

Simplified Mathematical Model for Effects of Freezing on the Low-Temperature Performance of the Lead-Acid Battery

Discharge periods of lead-acid batteries are significantly reduced at subzero centigrade temperatures. The reduction is more than what can he expected due to decreased rates of various processes caused by a lowering of temperature and occurs despite the fact that active materials are available for discharge. It is proposed that the major cause for this is the freezing of the electrolyte. The concentration of acid decreases during battery discharge with a consequent increase in the freezing temperature. A battery freezes when the discharge temperature falls below the freezing temperature. A mathematical model is developed for conditions where charge-transfer reaction is the rate-limiting step. and Tafel kinetics are applicable. It is argued that freezing begins from the midplanes of electrodes and proceeds toward the reservoir in-between. Ionic conduction stops when one of the electrodes freezes fully and the time taken to reach that point, namely the discharge period, is calculated. The predictions of the model compare well to observations made at low current density (C/5) and at -20 and -40 degrees C. At higher current densities, however, diffusional resistances become important and a more complicated moving boundary problem needs to be solved to predict the discharge periods. (C) 2009 The Electrochemical Society.

Two stage Gifford-McMahon cycle cryorefrigerator operating at 20 K

A two stage Gifford-McMahon cycle cryorefrigerator operating at 20 K is described. This refrigerator uses a very simple ‘spool valve’ and a modified indigenous compressor to compress helium gas. This cryorefrigerator reaches a lowest temperature of 15.5 K; it takes ≈ 50 min to reach 20 K and the cooling capacity is ≈ 2.5 W at 25 K. The cool-down characteristics and load characteristics are presented in graphical form. The effect of changing the operating pressure ratio and the second stage regenerator matrix size are also reported. Pressure-volume (P-V) diagrams obtained at various temperatures indicate that P-V losses form the major fraction of the total losses and this becomes more pronounced as the temperature is decreased. A heat balance analysis shows the relative magnitudes of various losses.

A fuzzy dynamic flood routing model for natural channels

A fuzzy dynamic flood routing model (FDFRM) for natural channels is presented, wherein the flood wave can be approximated to a monoclinal wave. This study is based on modification of an earlier published work by the same authors, where the nature of the wave was of gravity type. Momentum equation of the dynamic wave model is replaced by a fuzzy rule based model, while retaining the continuity equation in its complete form. Hence, the FDFRM gets rid of the assumptions associated with the momentum equation. Also, it overcomes the necessity of calculating friction slope (S-f) in flood routing and hence the associated uncertainties are eliminated. The fuzzy rule based model is developed on an equation for wave velocity, which is obtained in terms of discontinuities in the gradient of flow parameters. The channel reach is divided into a number of approximately uniform sub-reaches. Training set required for development of the fuzzy rule based model for each sub-reach is obtained from discharge-area relationship at its mean section. For highly heterogeneous sub-reaches, optimized fuzzy rule based models are obtained by means of a neuro-fuzzy algorithm. For demonstration, the FDFRM is applied to flood routing problems in a fictitious channel with single uniform reach, in a fictitious channel with two uniform sub-reaches and also in a natural channel with a number of approximately uniform sub-reaches. It is observed that in cases of the fictitious channels, the FDFRM outputs match well with those of an implicit numerical model (INM), which solves the dynamic wave equations using an implicit numerical scheme. For the natural channel, the FDFRM Outputs are comparable to those of the HEC-RAS model.

Estrogen modulation of retinol-binding protein in immature chicks: Comparison with riboflavin carrier protein

The kinetics of estrogen (E) modulation of retinol-binding protein (RBP) production in the liver of immature chicks were compared with those governing de novo induction of riboflavin carrier protein (RCP) in the same tissue. A single dose of E markedly enhanced the plasma levels of RBP without any detectable lag period to reach peak value by 24 h and this was followed by a decline to attain the baseline by 4 days. There was no amplification of the response during secondary stimulation unlike the case with RCP induction. With multiple E administration, the 4-fold increased plasma RBP concentrations were sustained at a steady state during both primary and secondary stimulations, whereas concomitant RCP concentration progressively increased with each hormone administration and this response was further amplified during secondary stimulation. Unlike RCP induction, enhanced RBP accumulation was not strictly E dose dependent although a minimal threshold level of the steroid was required to elicit measurable response. Progesterone (P) could neither modulate nor substitute for E in enhancing plasma levels of either of the 2 proteins while the anti-estrogens, en- and zuclomifene citrate severely suppressed the production of both the proteins. RCP induction was completely inhibited by both α-amanitin and cycloheximide for prolonged periods while E-stimulated RBP production was affected only partially by α-amanitin. Likewise, cycloheximide inhibition of RBP accumulation followed a pattern similar to that of hepatic general protein synthesis.

Flow over a cylinder with a hinged-splitter plate

Previous work on rigid splitter plates in the wake of a bluff body has shown that the primary vortex shedding can be suppressed for sufficiently long splitter plates. In the present work, we study the problem of a hinged-splitter plate in the wake of a circular cylinder. The splitter plate can rotate about the hinge at the base of the cylinder due to the unsteady fluid forces acting on it, and hence the communication between the two sides of the wake is not totally disrupted as in the rigid splitter plate case. In our study, we investigate this problem in the limit where the stiffness and internal damping associated with the hinge are negligible, and the mass ratio of the splitter plate is small. The experiments show that the splitter plate oscillations increase with Reynolds numbers at low values of Re, and are found to reach a saturation amplitude level at higher Re, Re>4000. This type of saturation amplitude level that appears to continue indefinitely with Re, appears to be related to the fact that there is no structural restoring force, and has been observed previously for transversely oscillating cylinders with no restorin force. In the present case, the saturation tip amplitude level can be tip to 0.45D, where D is the cylinder diameter. For this hinged-rigid splitter plate case, it is found that the splitter plate length to cylinder diameter ratio (L/D) is crucial in determining the character and magnitude of the oscillations. For small splitter plate length (L/D <= 3.0), the oscillations appear to be nearly periodic with tip amplitudes of about 0.45D nearly independent of L/D. The nondiinensional oscillation frequencies (fD/U) on the other hand are found to continuously vary with L/D from fD/U approximate to 0.2 at L/D = 1 to fD/U approximate to 0.1 at L/D = 3. As the splitter plate length is further increased beyond L/D >= 4.0, the character of the splitter plate oscillations suddenly changes. The oscillations become aperiodic with much smaller amplitudes. In this long splitter plate regime, the spectra of the oscillations become broadband, and are reminiscent of the change in character of the wake oscillations seen in the earlier fixed-rigid splitter plate case for L/D >= 5.0. In the present case of the hinged-splitter plate, the sudden transition seen as the splitter plate length (L/D) is increased from 3 to 4 may be attributed to the fact that the wake vortices are no longer able to synchronize with the plate motions for larger splitter plate lengths. Hence, as observed in other vortex-induced vibration problems, the oscillations becomeaperiodic and the amplitude reduces dramatically.

A conformational approach to the study of the dynamics of enzyme inhibition: studies on thermolysin

The preferred conformations of β-phenylpropionyl-Image -phenylalanine (β-PPP) and N-carbobenzoxy-L-phenylalanine (Cbz-Phe), two inhibitors of thermolysin, have been determined by computing potential energy using empirial potential energy functions. Of the 15 to 20 conformations that are favoured for each of these inhibitors only a few have the right conformation to reach the active site of the enzyme. The conformer of β-PPP that initiates binding with the enzyme is different from the bound one, while for Cbz-Phe the bound and initiating conformers are quite similar. Thus, β-PPP favours the ‘induced fit’ model while Cbz-Phe follows the ‘lock and key’ model of binding. The inhibitors differ in their alignment at the active site.

Dynamics of Circulating Concentrations of Gonadotropins and Ovarian Hormones Throughout the Menstrual Cycle in the Bonnet Monkey: Role of Inhibin A in the Regulation of Follicle-Stimulating Hormone Secretion

In higher primates, increased circulating follicle-stimulating hormone (FSH) levels seen during late menstrual cycle and during menstruation has been suggested to be necessary for initiation of follicular growth, recruitment of follicles and eventually culminating in ovulation of a single follicle. With a view to establish the dynamics of circulating FSH secretion with that of inhibin A (INH A) and progesterone (P-4)secretions during the menstrual cycle, blood was collected daily from bonnet monkeys beginning day 1 of the menstrual cycle up to 35 days. Serum INH A levels were low during early follicular phase, increased significantly coinciding with the mid cycle luteinizing hormone (LH) surge to reach maximal levels during the mid luteal phase before declining at the late luteal phase, essentially paralleling the pattern Of P-4 secretion seen throughout the luteal phase. Circulating FSH levels were low during early and mid luteal phases, but progressively increased during the late luteal phase and remained high for few days after the onset of menses. In another experiment, lutectomy performed during the mid luteal phase resulted in significant decrease in INH A concentration within 2 hr (58.3 +/- 2 vs. 27.3 +/- 3 pg/mL), and a 2- to 3-fold rise in circulating FSH levels by 24 hr (0.20 +/- 0.02 vs. 0.53 +/- 0.14 ng/mL) that remained high until 48 hr postlutectomy. Systemic administration of Cetrorelix (150 mu g/kg body weight), a gonadotropin releasing hormone receptor antagonist, at mid luteal phase in monkeys led to suppression of serum INH A and P-4 concentrations 24 hr post treatment, but circulating FSH levels did not change. Administration of exogenous LH, but not FSH, significantly increased INH A concentration. The results taken together suggest a tight coupling between LH and INH A secretion and that INH A is largely responsible for maintenance of low FSH concentration seen during the luteal phase. Am. J. Primatol. 71:817-824, 2009.

Location of Pathogenic Bacteria during Persistent Infections: Insights from an Analysis Using Game Theory

Bacterial persistent infections are responsible for a significant amount of the human morbidity and mortality. Unlike acute bacterial infections, it is very difficult to treat persistent bacterial infections (e.g. tuberculosis). Knowledge about the location of pathogenic bacteria during persistent infection will help to treat such conditions by designing novel drugs which can reach such locations. In this study, events of bacterial persistent infections were analyzed using game theory. A game was defined where the pathogen and the host are the two players with a conflict of interest. Criteria for the establishment of Nash equilibrium were calculated for this game. This theoretical model, which is very simple and heuristic, predicts that during persistent infections pathogenic bacteria stay in both intracellular and extracellular compartments of the host. The result of this study implies that a bacterium should be able to survive in both intracellular and extracellular compartments of the host in order to cause persistent infections. This explains why persistent infections are more often caused by intracellular pathogens like Mycobacterium and Salmonella. Moreover, this prediction is in consistence with the results of previous experimental studies.