Extracellular signal-regulated kinase 1/2 plays a pro-life role in experimental brain stem death via MAPK signal-interacting kinase at rostral ventrolateral medulla

<p>Abstract</p> <p>Background</p> <p>As the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life) and decreases (pro-death) to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate for mechanistic delineation of this fatal phenomenon. The present study assessed the hypothesis that extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinases (MAPKs) that is important for cell survival and is activated specifically by MAPK kinase 1/2 (MEK1/2), plays a pro-life role in RVLM during brain stem death. We further delineated the participation of MAPK signal-interacting kinase (MNK), a novel substrate of ERK in this process.</p> <p>Methods</p> <p>An experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol) bilaterally into RVLM of Sprague-Dawley rats was used, in conjunction with cardiovascular, pharmacological and biochemical evaluations.</p> <p>Results</p> <p>Results from ELISA showed that whereas the total ERK1/2 was not affected, augmented phosphorylation of ERK1/2 at Thr202 and Tyr204 in RVLM occurred preferentially during the pro-life phase of experimental brain stem death. Furthermore, pretreatment by microinjection into the bilateral RVLM of a specific ERK2 inhibitor, ERK activation inhibitor peptide II (1 nmol); a specific MEK1/2 inhibitor, U0126 (5 pmol); or a specific MNK1/2 inhibitor, CGP57380 (5 pmol) exacerbated the hypotension and blunted the augmented life-and-death signals exhibited during the pro-life phase. Those pretreatments also blocked the upregulated nitric oxide synthase I (NOS I)/protein kinase G (PKG) signaling, the pro-life cascade that sustains central cardiovascular regulatory functions during experimental brain stem death.</p> <p>Conclusions</p> <p>Our results demonstrated that activation of MEK1/2, ERK1/2 and MNK1/2 in RVLM plays a preferential pro-life role by sustaining the central cardiovascular regulatory machinery during brain stem death via upregulation of NOS I/PKG signaling cascade in RVLM.</p

Effects of annealing on the electrical properties of Fe-doped InP

The electrical properties of Fe-doped semi-insulating (SI) InP were investigated before and after annealing. The annealing conditions were controlled by changing either the temperature or duration. Correlation between the change of electrical parameters with the change of defect concentration at different annealing stage was observed. The defects and the change of the concentrations in Fe-doped SI InP were detected by room-temperature photocurrent spectroscopy.published_or_final_versio

Thermally induced conduction type conversion in n-type InP

n-type semiconducting InP is changed into p-type semiconducting by short time annealing at 700 °C. Further annealing for a longer time leads to a second conduction-type conversion changing the material back to n type again but with a much higher resistivity. These conduction conversions indicate the formation of both acceptor and donor defects and the progressive variation of their relative concentrations during annealing. © 1999 American Institute of Physics.published_or_final_versio

Positron-annihilation study of compensation defects in InP

Positron-annihilation lifetime and positron-annihilation Doppler-broadening (PADB) spectroscopies have been employed to investigate the formation of vacancy-type compensation defects in n-type undoped liquid encapsulated Czochrolski grown InP, which undergoes conduction-type conversions under high temperature annealing. N-type InP becomes p-type semiconducting by short time annealing at 700°C, and then turns into n-type again after further annealing but with a much higher resistivity. Long time annealing at 950°C makes the material semi-insulating. Positron lifetime measurements show that the positron average lifetime τ av increases from 245 ps to a higher value of 247 ps for the first n-type to p-type conversion and decreases to 240 ps for the ensuing p-type to n-type conversion. The value of τ av increases slightly to 242 ps upon further annealing and attains a value of 250 ps under 90 h annealing at 950°C. These results together with those of PADB measurements are explained by the model proposed in our previous study. The correlation between the characteristics of positron annihilation and the conversions of conduction type indicates that the formation of vacancy-type defects and the progressive variation of their concentrations during annealing are related to the electrical properties of the bulk InP material. © 2002 American Institute of Physics.published_or_final_versio

Positron-lifetime study of compensation defects in undoped semi-insulating InP

Positron-lifetime and infrared-absorption spectroscopies have been used to investigate the compensation defects that render undoped n-type liquid encapsulated Czochralski-grown InP semi-insulating under high-temperature annealing. The positron measurements, carried out over the temperature range of 25-300 K, reveal in the as-grown material a positron lifetime of 282±5 ps which we associate with either the isolated indium vacancy V 3- In or related hydrogen complexes. The shallow donor complex V InH 4, responsible for much of the n-type conductivity and the strong infrared absorption signal at 4320 nm, is ruled out as a significant trapping site on the grounds that its neutral state is present at too low a concentration. After annealing at 950°C, in conjunction with the disappearance of the V InH 4 infrared-absorption signal, trapping into V In-related centers is observed to increase slightly, and an additional positron trapping defect having a lifetime of 330 ps appears at a concentration of ∼10 16 cm -3, indicating divacancy trapping. These results support the recent suggestion that the V InH 4 complex present in as-grown InP dissociates during annealing, forming V InH (3-n)- n (0≤n≤3) complexes and that the recombination of V In with a phosphorus atom results in the formation of EL2-like deep donor P In antisite defect, which compensates the material. It is suggested that the divacancy formed on annealing is V InV P, and that this defect is probably a by-product of the P In antisite formation.published_or_final_versio

Electrical and FT-IR measurements of undoped N-type INP materials grown from various stoichiometric melts

P-rich, In-rich and Stoichiometric undoped InP melts have been synthesed by phosphorus in-situ injection method. InP crystal ingots have been grown from these melts by Liquid Encapsulated Czochralski (LEC). Samples from these ingots grown from various Stoichiometric melts have been characterized by Hall Effect and Fourier Transform Infrared (FT-IR) spectroscopy measurements respectively. The Hall Effect measurement results indicate that the net carrier concentration of P-inch undoped InP is higher than that of In-rich and Stoichiometric undoped InP materials. FT-IR spectroscopy measurements reveal that there are intensive absorption peaks which have been proved to be hydrogen related indium vacancy complex V InH 4. By comparing FT-IR spectra, it is found that P-rich InP material has the most intensive absorption peak of V InH 4, while In-rich InP material has the weakest absorption peak.published_or_final_versio

Native donors and compensation in Fe-doped liquid encapsulated Czochralski InP

Undoped and Fe-doped liquid encapsulated Czochralski (LEC) InP has been studied by Hall effect, current-voltage (I-V), and infrared absorption (IR) spectroscopy. The results indicate that a native hydrogen vacancy complex donor defect exists in as-grown LEC InP. By studying the IR results, it is found that the concentration of this donor defect in Fe-doped InP is much higher than that in undoped InP. This result is consistent with the observation that a much higher concentration of Fe 2+ than the apparent net donor concentration is needed to achieve the semi-insulating (SI) property in InP. By studying the I-V and IR results of Fe-doped InP wafers sliced from different positions on an ingot, the high concentration of Fe 2+ is found to correlate with the existence of this hydrogen complex. The concentration of this donor defect is high in wafers from the top of an ingot. Correspondingly, a higher concentration of Fe 2+ can be detected in these wafers. These results reveal the influence of the complex defect on the compensation and uniformity of Fe-doped SI InP materials. © 2001 American Institute of Physics.published_or_final_versio

Compensation defects in annealed undoped liquid encapsulated Czochralski InP

As-grown undoped n-type semiconducting and annealed undoped semi-insulating (SI) liquid encapsulated Czochralski (LEC) InP has been studied by temperature dependent Hall measurement, photoluminescence spectroscopy, infrared absorption, and photocurrent spectroscopy. P-type conduction SI InP can frequently be obtained by annealing undoped LEC InP. This is caused by a high concentration of thermally induced native acceptor defects. In some cases, it can be shown that the thermally induced n-type SI property of undoped LEC InP is caused by a midgap donor compensating for the net shallow acceptors. The midgap donor is proposed to be a phosphorus antisite related defect. Traps in annealed SI InP have been detected by photocurrent spectroscopy and have been compared with reported results. The mechanisms of defect formation are discussed. © 1999 American Institute of Physics.published_or_final_versio