Initial Pressure Values Research Articles

A comparison of the effects of perindopril arginine and amlodipine on choroidal thickness in patients with primary hypertension

This study aimed to investigate the effects of two different medical treatment options on choroidal thickness (CT) in patients with primary hypertension. Forty newly diagnosed primary hypertension patients and 21 healthy volunteers were included. The patients were randomly divided into two subgroups. Group I started on perindopril arginine and Group II started on amlodipine. Submacular CT using optical coherence tomography (OCT) was measured before treatment and at the third and sixth months after treatment. Initial mean arterial pressure (MAP) values in Groups I and II and the control group were 113.4, 109.8, and 89.4 mmHg, respectively, and mean CT values were 257.9, 286.5, and 300.9 μm. Mean MAP values in Groups I and II and the control group at the sixth month after treatment were 99.7, 99.6, and 90.2 mmHg, respectively, and mean CT values were 293.1, 286, and 297.4 μm. Analysis of the changes occurring during the study revealed significant variation in MAP in Groups I and II, and in CT in Group I only. A gradual increase in CT developed with perindopril arginine therapy in patients with primary hypertension, while no significant change occurred in CT in the amlodipine group.

Comparative model study of mechanical resistance of intestinal and stomach walls to the pressure in the device prototype for circular anastomosis

Background. The vital margins of the gut wall squee­zing, which is observed in cases of functional distension, negative pressure wound therapy or magnetic anastomosis device placing, ranged from 0.005 to 0.4 N/m2. The desirable short-time formation of structural connection in anastomotic line due to radio frequency electric influence, obviously, requires not vital, but a tight compression of the intestine wall on the verge of its structural deformation. C. Holmer et al. established the optimal value of electrode pressure onto the porcine intestine close to 1,125 mN/mm2. In our experiments, compression range of 2–6 · 104 N/m2 was found as more favorable for the radio frequency electric welding connection in anastomosis of the hollow organs. The purpose was to study the mechanical resistance of gut and stomach walls for comparative projection on its structural changes under strong pressure at the anastomosis model conditions. Materials and methods. The porcine intestine and stomach were delivered from the farm to laboratory during 6 hours in 4 оС and then heated in 0.9% NaCl up to 26–32 оС [6]. Two organ walls were placed inside the prototype device for human circular anastomosis, and then pressed for 60 seconds before radio frequency welding. The 117 probes were made in several combinations investigating pressure values 2.1, 3.0, 3.9 and 6.0 N/mm2 (or · 104 N/m2) effect for organ wall by connected micrometer device. Results. The wall thinning time, which is inversely proportional to resistance, visually divided into two phases: the fast (1–5 s) and significant thinning of the tissue after initial pressure application, then slow and low-amplitude thinning. The small intestine wall resistance was higher than the stomach one as well as the combination of the stomach and intestinal under all values of initial pressure. Conclusions. The first compression phase is unique according to the thinned organ. Some thinning rate decrease occurred at the second phase under the pressure 3.0–3.9 N/mm2 comparing to 2.1 N/mm2 up to 60 seconds, determines the limit of mechanical resistance of the wall muscle layer as well as overall gut and stomach integrity up to such pressure level. Obtained data helps to project the structural changes inside intestinal and/or stomach walls compressed into circular anastomotic device, which is important for the planning of further effects.

A small-scale experimental study on the initial burst and the heterogeneous evolution process before CO2 BLEVE

The sudden rupture of a vessel containing liquefied carbon dioxide (CO2) can generate a boiling liquid expanding vapor cloud explosion (BLEVE). The entire evolution process and mechanism of CO2 BLEVE has not been fully characterized, and its influencing factors have not been systematically examined. In this study, the ejection process and microphase change process in the vessel were recorded by a high-speed camera. Within 20ms, the pressure peaks surpassed the initial values and were considered to be the initiation of a sequence that generated a CO2 BLEVE under certain conditions. In addition, a critical relief caliber with a diameter of 8mm was observed under the initial burst pressures of 3 and 5MPa. This critical relief caliber is essential for risk control and management. About 52ms after the rupture, a heterogeneous nucleation center was formed in the liquefied CO2 in the vessel. Subsequent nucleation center extension and swelling generated another pressure peak. The pressure peak did not surpass the initial pressure value. However, this phenomenon did not eliminate any possible connections between the heterogeneous nucleation process and the CO2 BLEVE. If the conditions had been proper, the explosion could have happened.

Process window calculation and pressure locus optimization in hydroforming of conical box with double concave cavities

With the enhancement in the functional integration of components and concentration on lightweight materials, complex sheet metal parts are widely used in automobile and aviation industrial clusters. Consequently, the sheet hydroforming process has become an attractive fabricating technology for forming lightweight materials and complicated products. In this research, the hydrodynamic deep drawing (HDD) process of a composite conical box with double concave cavities was investigated through theoretical analysis, numerical simulation, and process experimentation. Furthermore, the process window diagram (PWD) was calculated using the stress analytical model combining material properties with workpiece geometrical features. The influence of cavity pressure loading locus on the forming quality of the fabricated part and the deformation behavior of aluminum alloy was explored. The forming results indicated that the initial pressure, full pressure, and loading locus are the fundamental parameters directly related to the forming quality and dimensional accuracy. For the conical part with composite features, the reasonable initial pressure value is crucial for the thickness homogeneity of the double concave characteristics, whereas the magnitude of the full pressure is vital for improving the quality of the conical feature. In addition, the optimal loading locus of the cavity pressure is characterized by two turning points, which are related to the punch corner radius, die shoulder radius, blank thickness, and angle of the conical feature.

Comparison of the effects of four different cochlear implant electrodes on intra-cochlear pressure in a model

Conclusion: Based on this model experiment, a small tip and low volume electrode show lowest intra-cochlear pressure values. Insertional support by a tool minimizes fast pressure changes. Higher electrodes volumes affect slow and fast pressure changes as well.Objective: Insertion causing low intra-cochlear pressure is assumed to be important for atraumatic cochlear implant surgery to preserve residual hearing. Cochlear implant electrodes differ in terms of parameters like tip size, length, volume, and technique of insertion. The aim of this study was to observe the effect of different cochlear implant electrodes on insertional intra-cochlear pressure in a cochlear model.Materials and methods: Cochlear implant electrode insertions were performed in an artificial cochlear model and intra-cochlear pressure changes were recorded in parallel with a micro-pressure sensor positioned in the apical region of the cochlear model to follow the maximum values, temporal changes, maximum amplitude, and frequency of changes in intra-cochlear pressure. Insertions were performed with four different electrodes (Advanced Bionics 1j, Helix, HFMS, and LW23).Results: This study found statistically significant differences in the occurrence of initial maximum pressure values correlating with the electrode tip size. The different electrodes and the technique of insertion significantly affected the occurrence of maximum value, amplitude, and frequency of intra-cochlear pressure occurrence.

An investigation for standardized diagnosis and treatment of idiopathic normal-pressure hydrocephalus

To investigate some important issues for diagnosis and treatment of idiopathic normal-pressure hydrocephalus (iNPH), such as standardized pre-operative assessment, initial pressure value of diverter pump, and pressure regulation during follow-up. Twenty six iNPH patients (21 males) who treated in Department of Neurosurgery of 2nd Affiliated Hospital of Zhejiang University School of Medicine from 2011 to 2015 were analyzed retrospectively. The average age was 60.5 year. The analysis focused on the treatment process of iNPH, initial pressure value of diverter pump, choice of diverter pump, and pressure regulation during follow-up. As a result, 24 cases (92.3%) had a good prognosis based on their imaging and clinical manifestations. Based on the literature and their clinical experiences, this department established a diagnosis and treatment procedure of iNPH and a pressure regulation procedure for the follow-up of iNPH. Moreover, it is proposed that choosing an anti-gravity diverter pump and making an initial pressure value 20 mmH2O less than pre-surgical cerebrospinal pressure may be beneficial for the prognosis. This standardized diagnosis and treatment procedure for iNPH is practical and effective.

Simulations of flashing experiments in TOPFLOW facility with TRACE code

The decompression experiments performed at TOPFLOW facility in 2010 have been reproduced using the latest best-estimate thermohydraulic system code TRACE (V 5.0 Patch 3). The main component of TOPFLOW facility was about 8m long vertical tube with an inner diameter of 195.3mm. The evaporation of liquid water to steam caused by depressurization was simulated using two different procedures: from stagnant water and during circulating of water in tubes. The liquid water was almost saturated at initial pressure values of 1.0, 2.0, 4.0 and 6.5MPa. Our approach applies one-dimensional code to simulate all the important parts of the facility not just the vertical test section, where the measurements were taken. The obtained simulated pressure, temperature and void fractions are compared with measured values. The simulations of the first procedure (stagnant water at beginning) are in a good agreement with measurements, especially for the cases with longer transients and higher initial pressure, however, choked flow model through the blow-off valve had to be adjusted. There is a short transient (about 2s) after the fast opening valve opens, which was not reproduced correctly with TRACE. The simulations of the second procedure (circulating water in a loop) correctly predict pressure and temperature decrease, but underpredict void fraction. No modification of the default TRACE choked flow model was needed for procedure B.

Calculating the caloric properties of dissociated steam at high temperatures

Lookup tables and the hs-diagram of the caloric parameters of dissociated steam are drawn up in the temperature and pressure ranges 1250–4000 K and 0.1–10 MPa for calculating the processes in thermal power installations that use dissociated steam as working fluid. Unlike the existing tables for thermophysical properties of dissociated steam, the enthalpy presented in the proposed tables has positive values in the entire range of the considered parameters. The enthalpy of mixture includes the entire energy spent in the chemical reaction of dissociation for breaking the bonds in steam molecules. The caloric parameters are determined from the reference temperature equal to 0°C adopted in the methods for calculating the parameters of nondissociated steam, due to which it becomes possible to carry out coordinated calculations of processes in thermal power installations. Supplements to the existing tables for calculating the above-mentioned caloric parameters are developed. Dissociated steam expansion processes are calculated for the conditions with and without recombination of dissociation products at the same values of initial parameters and final pressure. It has been determined that the change of enthalpy and the work done in the expansion process without recombination are smaller than they are in the process involving recombination of dissociation products. The error of the performed calculations of caloric parameters is less than 0.1%.

An association between systolic blood pressure and stroke among patients with impaired consciousness in out-of-hospital emergency settings

BackgroundStroke is difficult to diagnose when consciousness is disturbed. However few reports have discussed the clinical predictors of stroke in out-of-hospital emergency settings. This study aims to evaluate the association between initial systolic blood pressure (SBP) value measured by emergency medical service (EMS) and diagnosis of stroke among impaired consciousness patients.MethodsWe included all patients aged 18 years or older who were treated and transported by EMS, and had impaired consciousness (Japan Coma Scale ≧ 1) in Osaka City (2.7 million), Japan from January 1, 1998 through December 31, 2007. Data were prospectively collected by EMS personnel using a study-specific case report form. Multiple logistic regressions assessed the relationship between initial SBP and stroke and its subtypes adjusted for possible confounding factors.ResultsDuring these 10 years, a total of 1,840,784 emergency patients who were treated and transported by EMS were documented during the study period in Osaka City. Out of 128,678 with impaired consciousness, 106,706 who had prehospital SBP measurements in the field were eligible for our analyses. The proportion of patients with severe impaired consciousness significantly increased from 14.5% in the <100 mmHg SBP group to 27.6% in the > =200 mmHg SBP group (P for trend <0.001). The occurrence of stroke significantly increased with increasing SBP (adjusted odd ratio [AOR] 1.34, 95% confidence interval [CI] 1.33 to 1.35), and the AOR of the SBP > =200 mmHg group versus the SBP 101-120 mmHg group was 5.26 (95% CI 4.93 to 5.60). The AOR of the SBP > =200 mmHg group versus the SBP 101-120 mmHg group was 9.76 in subarachnoid hemorrhage (SAH), 16.16 in intracranial hemorrhage (ICH), and 1.52 in ischemic stroke (IS), and the AOR of SAH and ICH was greater than that of IS.ConclusionsElevated SBP among emergency patients with impaired consciousness in the field was associated with increased diagnosis of stroke.

The analysis of the calculation process related to labyrinth sealing with extraction

The work presents a calculation process enabling one-dimensional numerical calculations of labyrinth sealing. A DSV program determines the thermodynamic parameters of gas in the sealing chambers with extraction. The influence of the sealing length upon the stability of a matrix solution of the system of equations with the use of Cond(C) parameter is analysed. Next, the operation of the software extended with a module that enables determination of the initial pressure p0, to which the assumed mass flow for a set geometry and sealing length would correspond is discussed. The work analyzes Cond(C) and initial pressure values for various sealing lengths with an assumed leak value. The work also compares the values of static pressures on the extraction plane, as obtained from the measurements, to theoretically calculated values. The calculations and comparisons were made for various heights of incomplete sealing fissures

Severity and control of hypertension during chronic kidney disease in Cameroon

Introduction. The association of hypertension with chronic kidney disease increases the morbidity and mortality. The aim of this study was to evaluate severity and control of hypertension among chronic kidney disease patients in Cameroon. Materials and methods. This was a cross sectional study on 97 medical files of patients suffering of hypertension and chronic kidney dis- ease at stages 3 to 5 not undergoing dialysis, in whom the treatment of hypertension was prescribed and followed during 8 weeks in outpa- tient nephrology clinics at Yaoundé general hospital. Results. The mean age of patients was 52.2±13.1 years with sex ratio 2:1. Severe hypertension occurred in 82 patients (84.6%) and 65 pa- tients (67%) had stage 4 to 5 chronic kidney disease. Renin angiotensin aldosterone blockers (89%), diuretics (80%) and calcium channel blockers (72%) were the main antihypertensive drugs. The mean number of antihypertensive drugs was 2.9±1.7 per patient and 70 patients (72.2%) were taking at least three antihypertensive drugs. At the end of the study, only 9 patients (9.3%) reached the target blood pressure value, and systolic and diastolic blood pressure reduction was respectively 36.3 mmHg and 19.4 mmHg. The severity of initial blood pressure value was statistically associated with poor control of blood pressure (p=0.004). Conclusion. Two third of patients at an advanced stage of chronic kidney disease were presenting with severe hypertension requiring the prescription of three antihypertensive drugs leading to poor short term control.

Applying Rate Transient Analysis (RTA) to integrate geological and engineering data

The Blasingame typecurve in Fekete’s Rate Transient Analysis (RTA) software has been used at Santos to increase the understanding and integration of well and reservoir data; however, the authors have discovered that in some cases the tool produced anomalous results, such as permeability being too low. The potential consequence of this was incorrectly writing off reserves or making projects (in particular compression projects) fail economic tests. After testing various hypotheses, a simple yet unorthodox solution was only discovered in a field where the anomaly was more profound, and required integrating geology and geophysics to explain it. This solution has since been applied in RTA models across numerous other fields, and it has improved the quality and confidence of these models. The solution was the realisation that in many cases the accessed gas in place (GIP) increased over time, but the underlying model in RTA assumes a single tank, linear P/z. Matching the RTA model with the initial reservoir pressure and final accessed GIP results in over-predicting the reservoir pressures, resulting in an artificially low permeability. The authors discovered that the appropriate well and reservoir parameters could be obtained by matching the late time data using a lower initial reservoir pressure value corresponding to when the well had accessed the final GIP volume but not the initial reservoir pressure. This step was initially regarded to be counter-intuitive as the initial pressure is a measured property. Numerous reviews have endorsed this methodology, which is now being used as a standard at Santos.

Mixed layers of DPPC and a linear poly(ethylene glycol)-b-hyperbranched poly(glycerol) block copolymer having a cholesteryl end group

Interactions of the phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) with the amphiphilic diblock copolymer Ch-lPEG30-b-hbPG24 (ChP) are studied at the air–water interface by surface pressure–mean molecular area (π–mmA) measurements of mixed Langmuir films and adsorption measurements of ChP to the air–water interface covered with DPPC monolayers at different initial surface pressure values π0. ChP is composed of a single hydrophobic cholesteryl (Ch) moiety covalently bound to a diblock copolymer consisting of a hydrophilic linear poly(ethylene glycol) (lPEG) block and a hydrophilic hyperbranched poly(glycerol) (hbPG) block. Langmuir isotherms and compression moduli of the mixed Langmuir films of different molar ratios reveal distinct interactions between DPPC and ChP during compression. It is demonstrated that the behavior of the DPPC/ChP mixtures is dominated by DPPC up to a molar ratio of 10:1, whereas the behavior is predominantly governed by ChP in mixtures with lower DPPC content (molar ratios of 5:1, 2:1, and 1:1). In adsorption measurements, a strong affinity of ChP to DPPC is observed after injection into the water subphase. The surface pressure value πin up to which ChP is able to penetrate into DPPC monolayers is determined to the remarkably high value of 48.2 mN/m which attests the favorable interactions between DPPC and the Ch moiety of ChP. Atomic force microscopy on LB films of DPPC/ChP mixtures of different molar ratios transferred onto hydrophilic substrates confirms the presence of two different phases, a DPPC-rich phase and a ChP-rich phase.

The autoignition in air of some binary fuel mixtures containing hydrogen

A predictive model for the autoignition and combustion of fuel–air mixtures employing detailed full chemical schemes was used to examine the autoignition and combustion characteristics in air of hydrogen in the presence of a range of common fuels. These included the gaseous fuels: methane, carbon monoxide and the higher hydrocarbon fuel n-heptane. A wide range of relative concentrations of the fuel components in the binary mixtures with hydrogen for different values of initial mixture temperature and pressure were considered under constant volume adiabatic conditions. It is shown that the presence of hydrogen in turn with these fuels can bring about complex changes to the autoignition behaviour of the fuel mixtures that show hydrogen may behave as an accelerant or retardant depending on the fuel, initial temperature, pressure and equivalence ratio considered.

Hemolytic Uremic Syndrome: Epidemiological and Clinical Features of a Pediatric Population in Tuscany

We retrospectively analyzed etiological, pathological and clinical features of the patients with hemolytic uremic syndrome (HUS) observed in the Pediatric Nephrology Unit at AOU Meyer of Florence. From January 1997 to December 2008, 22 cases were identified, with an annual incidence of 0.05 cases per 100,000 inhabitants, and 0.34 cases per 100,000 children <15 years old. 60% of the patients were D+ and 40% were D–, with an age distribution from 12 days to 13 years. Twenty patients (90%) had oligoanuria, lasting 6.4 ± 4 days for D+ patients versus 11.8 ± 4 days for D– patients. The development of chronic kidney disease positively correlates with the initial blood pressure value, the length of oligoanuria, and hospitalization. Microbiological investigations showed an association of D+HUS with different strains of Shiga toxin-producing Escherichia coli in 54% of the cases. D–HUS was associated with complement factor H deficiency in one patient. In the other cases, the triggering factors were pertussis, urinary tract infections and upper airway infections. While clinical and prognostic features correspond with literature data, in Tuscany the annual incidence is lower, and the percentage of D–HUS patients is higher than that observed in other studies.

Well Testing of Tight Gas Reservoirs

Abstract A tight gas reservoir is commonly defined as a reservoir having less than 0.1 milliDarcies permeability. Because of the very low permeability, hydraulic fracturing is usually carried out in efforts to establish commercial production. There are several basic concepts and field cases of different well tests in tight gas reservoirs in the literature. In this paper, we gather information and provide a guide to some of the most important tests. Generally because of low permeability, a well will not flow initially at measurable rates and conventional well testing cannot be applied. We review procedures for design of pre- and postfracture tests in single and dual porosity reservoirs. The prefracture test permits estimating preliminary values of reservoir permeability and initial pressure. The post-fracture test provides data for estimating fracture half length and conductivity. We also review the application of convolution/deconvolution methods to analyze well tests with significant wellbore storage. Because of economic and environmental reasons, short duration procedures are preferred. However, although effective in many instances, these methods also have their own limitations. Introduction Unconventional reservoirs (tight gas, coal bed methane, shales gas and gas hydrates) will be an important pat of the global energy mix for decades to come. Large reserves, long-term potential, costs and gas prices and some other factors account for the great influence of these resources on the future of energy. There is no formal definition for "tight gas." A commonly used definition, describes tight gas reservoirs as those having permeabilities smaller than 0.1 milliDarcies. Well testing is generally done as an aid to estimate gas in-place and recoverable volumes. Initial pressure (pi) is a critical parameter not only for estimating gas in-place, but also for determining how much field development is required and whether or not the field is overdeveloped. In addition to pi, well testing provides an estimate of permeability and skin. A problem associated with well testing in tight gas sands is that usually long times are required to reach radial flow, due to their extremely low permeabilities. Therefore, conventional well tests cannot be applied to these reservoirs. Because of initial uneconomic rates, fracturing is usually required. Lee(2) has suggested procedures for pre- and post-fracture tests design. In order to have measurable gas rates for pre-frac testing, often a breakdown with acid, KCl water or N2 is necessary.

Endophilin B1/Bif-1 Stimulates BAX Activation Independently from Its Capacity to Produce Large Scale Membrane Morphological Rearrangements

Endophilin B1/BAX-interacting factor 1 (Bif-1) is a protein that cooperates with dynamin-like protein 1 (DLP1/Drp1) to maintain normal mitochondrial outer membrane (MOM) dynamics in healthy cells and also contributes to BAX-driven MOM permeabilization (MOMP), the irreversible commitment point to cell death for the majority of apoptotic stimuli. However, despite its importance, exactly how Bif-1 fulfils its proapoptotic role is unknown. Here, we demonstrate that the stimulatory effect of Bif-1 on BAX-driven MOMP and on BAX conformational activation observed in intact cells during apoptosis can be recapitulated in a simplified system consisting of purified proteins and MOM-like liposomes. In this reconstituted model system the N-BAR domain of Bif-1 reproduced the stimulatory effect of Bif-1 on functional BAX activation. This process was dependent on physical interaction between Bif-1 N-BAR and BAX as well as on the presence of the mitochondrion-specific lipid cardiolipin. Despite that Bif-1 N-BAR produced large scale morphological rearrangements in MOM-like liposomes, this phenomenon could be separated from functional BAX activation. Furthermore, DLP1 also caused global morphological changes in MOM-like liposomes, but DLP1 did not stimulate BAX-permeabilizing function in the absence or presence of Bif-1. Taken together, our findings not only provide direct evidence for a functional interplay between Bif-1, BAX, and cardiolipin during MOMP but also add significantly to the growing body of evidence indicating that components of the mitochondrial morphogenesis machinery possess proapoptotic functions that are independent from their recognized roles in normal mitochondrial dynamics.

Analytical Modeling of Hydraulically Expanded Tube-To-Tubesheet Joints

AbstractThe loss of the initial tightness during service is one of the major causes of failure of tube-to-tubesheet joints. The initial residual contact pressure and its variation during the lifetime of the joint are among the parameters to blame. A reliable assessment of the initial contact pressure value requires accurate and rigorous modeling of the elastoplastic behavior of the tube and the tubesheet during the expansion process. This paper deals with the development of a new analytical model used to accurately predict the residual contact pressure resulting from a hydraulic expansion process. The analytical model is based on the elastic perfectly plastic material behavior of the tube and the tubesheet and the interaction between these two elements of the expanded joint. The model results have been compared and validated with those of the more accurate finite element analysis models. Additional comparisons have been made with existing methods.

Dual-element directional shock wave attenuators

This study explores the interaction between shock waves and dual-element porous plates used to ameliorate the hazardous effects of these waves. Tests were performed in a shock tube to determine the effects that a pair of porous plates with directional resistance properties had on the initial peak pressure and impulse amelioration experienced by an end wall. Mild steel test specimens, ranging in porosity values from 6.6% to 41.1%, were mounted two at a time at different spacings in the test section. Each plate had directional properties, i.e. resistance to flow was different for flow coming from either side. Four plates were used, and 48 plate configurations were tested. Side wall and end wall pressure measurements and schlieren photographs were taken of the interactions. Tests were run at Mach numbers of 1.23, 1.35 and 1.42. The separation distances between the plate specimens were varied between 30 mm and 60 mm; however, the distance between the downstream plate and the end wall was kept constant at 140 mm for all tests. Both the initial peak pressure and impulse amelioration values were found to be dependant on the plate combination porosity. As the porosity of the combination increased, the amelioration values decreased. Complementary plate combinations produced differing results as different wave interactions occur when plate positions were interchanged. The porosity of the combined plates was found to have an overriding influence on the end wall peak pressure and impulse amelioration values when compared to the effect that plate arrangement (i.e. geometrical influences) had. Impulse amelioration values were found to increase as the separation distance between plates were increased. The amplitude of the end wall pressure trace was found to increase as the incident Mach number was increased. The significant attenuation of the incident shock wave obtained during this study is attributed to the system of multiple reflected and transmitted waves that are produced by the presence of the plate specimens in series. This increases the frequency of shock wave and barrier interactions, when compared to just using a single barrier.

BIM and tBID Are Not Mechanistically Equivalent When Assisting BAX to Permeabilize Bilayer Membranes

BIM and tBID are two BCL-2 homology 3 (BH3)-only proteins with a particularly strong capacity to trigger BAX-driven mitochondrial outer membrane permeabilization, a crucial event in mammalian apoptosis. However, the means whereby BIM and tBID fulfill this task is controversial. Here, we used a reconstituted liposomal system bearing physiological relevance to explore systematically how the BAX-permeabilizing function is influenced by interactions of BIM/BID-derived proteins and BH3 motifs with multidomain BCL-2 family members and with membrane lipids. We found that nanomolar dosing of BIM proteins sufficed to reverse completely the inhibition of BAX permeabilizing activity exerted by all antiapoptotic proteins tested (BCL-2, BCL-X(L), BCL-W, MCL-1, and A1). This effect was reproducible by a peptide representing the BH3 motif of BIM, whereas an equivalent BID BH3 peptide was less potent and more selective, reversing antiapoptotic inhibition. On the other hand, in the absence of BCL-2-type proteins, BIM proteins and the BIM BH3 peptide were inefficient, directly triggering the BAX-permeabilizing function. In contrast, tBID alone potently assisted BAX to permeabilize membranes at least in part by producing a structural distortion in the lipid bilayer via BH3-independent interaction of tBID with cardiolipin. Together, these results support the notion that BIM and tBID follow different strategies to trigger BAX-driven mitochondrial outer membrane permeabilization with strong potency.