Regulation of mesangial cell ion channels by insulin and angiotensin II. Possible role in diabetic glomerular hyperfiltration

We used patch clamp methodology to investigate how glomerular mesangial cells (GMC) depolarize, thus stimulating voltage-dependent Ca2+ channels and GMC contraction. In rat GMC cultures grown in 100 mU/ml insulin, 12% of cell-attached patches contained a Ca(2+)-dependent, 4-picosiemens Cl- channel. Basal NPo (number of channels times open probability) was < 0.1 at resting membrane potential. Acute application of 1-100 nM angiotensin II (AII) or 0.25 microM thapsigargin (to release [Ca2+]i stores) increased NPo. In GMC grown without insulin, Cl- channels were rare (4%) and unresponsive to AII or thapsigargin in cell-attached patches, and less sensitive to [Ca2+]i in excised patches. GMC also contained 27-pS nonselective cation channels (NSCC) stimulated by AII, thapsigargin, or [Ca2+]i, but again only when insulin was present. In GMC grown without insulin, 15 min of insulin exposure increased NPo (insulin > or = 100 microU/ml) and restored AII and [Ca2+]i responsiveness (insulin > or = 1 microU/ml) to both Cl- and NSCC. GMC AII receptor binding studies showed a Bmax (binding sites) of 2.44 +/- 0.58 fmol/mg protein and a Kd (binding dissociation constant) of 3.02 +/- 2.01 nM in the absence of insulin. Bmax increased by 86% and Kd was unchanged after chronic (days) insulin exposure. In contrast, neither Kd nor Bmax was significantly affected by acute (15-min) exposure. Therefore, we concluded that: (a) rat GMC cultures contain Ca(2+)-dependent Cl- and NSCC, both stimulated by AII. (b) Cl- efflux and cation influx, respectively, would promote GMC depolarization, leading to voltage-dependent Ca2+ channel activation and GMC contraction. (c) Responsiveness of Cl- and NSCC to AII is dependent on insulin exposure; AII receptor density increases with chronic, but not acute insulin, and channel sensitivity to [Ca2+]i increases with both acute and chronic insulin. (d) Decreased GMC contractility may contribute to the glomerular hyperfiltration seen in insulinopenic or insulin-resistant diabetic patients.     

A wireless controller to enhance dynamic performance of parallel inverters in distributed generation systems

This paper presents a novel control strategy for parallel inverters of distributed generation units in an AC distribution system. The proposed control technique, based on the droop control method, uses only locally measurable feedback signals. This method is usually applied to achieve good active and reactive power sharing when communication between the inverters is difficult due to its physical location. However, the conventional voltage and frequency droop methods of achieving load sharing have a slow and oscillating transient response. Moreover, there is no possibility to modify the transient response without the loss of power sharing precision or output-voltage and frequency accuracy. In this work, a great improvement in transient response is achieved by introducing power derivative-integral terms into a conventional droop scheme. Hence, better controllability of the system is obtained and, consequently, correct transient performance can be achieved. In addition, an instantaneous current control loop is also included in the novel controller to ensure correct sharing of harmonic components when supplying nonlinear loads. Simulation and experimental results are presented to prove the validity of this approach, which shows excellent performance as opposed to the conventional one.     

Wireless-Control Strategy for Parallel Operation of Distributed-Generation Inverters

In this paper, a method for the parallel operation of inverters in an ac-distributed system is proposed. This paper explores the control of active and reactive power flow through the analysis of the output impedance of the inverters and its impact on the power sharing. As a result, adaptive virtual output impedance is proposed in order to achieve a proper reactive power sharing, regardless of the line-impedance unbalances. A soft-start operation is also included, avoiding the initial current peak, which results in a seamless hot-swap operation. Active power sharing is achieved by adjusting the frequency in load transient situations only, owing to which the proposed method obtains a constant steady-state frequency and amplitude. As opposed to the conventional droop method, the transient response can be modified by acting on the main control parameters. Linear and nonlinear loads can be properly shared due to the addition of a current harmonic loop in the control strategy. Experimental results are presented from a two-6-kVA parallel-connected inverter system, showing the feasibility of the proposed approach     

Robust inference for one-shot device testing data under exponential lifetime model with multiple stresses

Introduced robust density-based estimators in the context of one-shot devices with exponential lifetimes under a single stress factor. However, it is usual to have several stress factors in industrial experiments involving one-shot devices. In this paper, the weighted minimum density power divergence estimators (WMDPDEs) are developed as a natural extension of the classical maximum likelihood estimators (MLEs) for one-shot device testing data under exponential lifetime model with multiple stresses. Based on these estimators, Wald-type test statistics are also developed. Through a simulation study, it is shown that some WMDPDEs have a better performance than the MLE in relation to robustness. Two examples with multiple stresses show the usefulness of the model and, in particular, of the proposed estimators, both in engineering and medicine.     

Ligand migration in sperm whale myoglobin

Geminate oxygen rebinding to myoglobin was followed from a few nanoseconds to a few microseconds after photolysis for more than 25 different oxymyoglobin point mutants in the presence and absence of 12 atm of xenon. In all cases, two relaxations were observed: an initial fast phase (half-time 20 ns) and a slower, smaller phase (half-time 0.5-2 micros). Generally, xenon accelerates the fast reaction but slows the slower reaction and diminishes its amplitude. The rates and proportions of the two components and the effects of xenon on them vary widely for different mutants. The locations of specific xenon binding sites [Tilton, R. F., Kuntz, I. D. Jr., and Petsko, G. A. (1984) Biochemistry 23, 2849-2857], the effects of point mutations on the geminate reactions, and molecular dynamics simulations were used to suggest locations in the protein interior occupied by ligands on the nanosecond to microsecond time scale. Photodissociated ligands may occupy xenon site 4 in the distal pocket and xenon site 1 below the plane of the heme. Rebinding from these positions corresponds to the slower geminate phase for O2 rebinding. The rapid geminate component is determined by competition between rebinding from a position closer to the iron atom and escape to solvent or more distant locations in the protein.     

Synthesis and cellular uptake of 2'-substituted analogues of (E)-5-(2-[125I]iodovinyl)-2'-deoxyuridine in tumor cells transduced with the herpes simplex type-1 thymidine kinase gene. Evaluation as probes for monitoring gene therapy

A useful synthetic methodology was developed to synthesize and radiolabel a series of (E)-5-(2-[125I]iodovinyl)uracil nucleoside substrates for herpes simplex virus type-1 thymidine kinase (HSV-1 TK). (E)-5-(2-[125I]Iodovinyl)-2'-deoxyuridine ([125I]IVDU, 10), (E)-5-(2-[125I]iodovinyl)-2'-fluoro-2'-deoxyuridine ([125I]IVFRU, 11), (E)-5-(2-[125I]iodovinyl)-2'-fluoro-2'-deoxyarabinouridine ([125I]IVFAU, 12), and (E)-5-(2-[125I]iodovinyl)arabinouridine ([125I]IVAU, 13) were synthesized in 63-83% radiochemical yield by reaction of the unprotected (E)-5-(2-(trimethylsilyl)vinyl) precursors (6-9) with [125I]ICl. Cellular uptake of these labeled compounds (10-13) was evaluated in vitro. All compounds showed minimal uptake in the KBALB cell line. However, increased uptake was observed for all compounds in KBALB-STK cells which are transduced with a replication incompetent Moloney murine leukemia virus vector encoding the HSV-1 TK gene. The results indicate that uptake of these compounds in KBALB-STK cells is variable and highly dependent on the nature of the sugar 2'-substituent. When a fluoro (12) or a hydroxy (13) substituent is present in the arabinofuranosyl (up) configuration at the 2'-position, there is diminished cellular uptake in KBALB-STK cells relative to hydrogen (10) or fluorine (11) in the ribofuranosyl (down) configuration at the 2'-position. Our results indicate that radiolabeled IVFRU (11) is most promising for further in vivo studies.     

Aortocaval fistula: diagnosis with MR angiography

A case of intramuscular hemangioma (large vessel type) occurring in an eighteen year old woman is described. Medical history reported a pulled muscle in the same region 5 years earlier. By needle biopsy was performed the diagnosis of hematoma evolved to sclerosis. Since pain persisted the neoplasia was removed. Intramuscular hemangioma is a benign neoplasia. Recurrences are always due to incomplete excision. Angiosarcomas and liposarcomas are the two tumors to be differentiated from hemangiomas of skeletal muscle. The relative paucity of cases combined with widespread histological pictures make the diagnosis very difficult.     

Valproate prophylaxis in a prospective clinical trial of refractory bipolar disorder

OBJECTIVE: The authors studied the efficacy of valproate plus lithium and of triple therapy with lithium, carbamazepine, and valproate in refractory bipolar illness. METHOD: The subjects were 24 bipolar outpatients who had completed an intended 3-year crossover study comparing lithium, carbamazepine, and their combination. Patients entered a 1-year phase of valproate plus lithium because of inadequate response or major side effects, and patients with inadequate responses were offered an additional year of treatment with all three mood-stabilizing drugs. RESULTS: Six (33%) of the 18 evaluable patients had moderate to marked responses to valproate plus lithium; four of these six had not responded to any previous treatment condition. Three of seven patients responded to triple therapy, although only one response was marked. CONCLUSIONS: Some outpatients with bipolar disorder refractory to lithium and carbamazepine received clinically relevant prophylactic benefit from valproate when used with lithium or in triple therapy.