Magnetism in single metalloorganic complexes formed by atom manipulation.

The magnetic properties of molecular structures can be tailored by chemical synthesis or bottom-up assembly at the atomic scale. We used scanning tunneling microscopy to study charge and spin transfer in individual complexes of transition metals with the charge acceptor, tetracyanoethylene (TCNE). The complexes were formed on a thin insulator, Cu2N on Cu(100), by manipulation of individual atoms and molecules. The Cu2N layer decouples the complexes from Cu electron density, enabling direct imaging of the TCNE molecular orbitals as well as spin-flip inelastic electron tunneling spectroscopy. Results were obtained at low temperature down to 1 K and in magnetic fields up to 7 T in order to resolve splitting of spin states in the complexes. We also performed spin-polarized density functional theory calculations to compare with the experimental data. Our results indicate that charge transfer to TCNE leads to a change in spin magnitude, Kondo resonance, and magnetic anisotropy for the metal atoms.

Proliferation of embryonic cardiomyocytes in zebrafish requires the sodium channel scn5Lab.

In mice, homozygous deletion of the cardiac sodium channel Scn5a results in defects in cardiac morphology and embryonic death before robust sodium current can be detected. In zebrafish, morpholino knockdown of cardiac sodium channel orthologs scn5Laa and scn5Lab perturbs specification of precardiac mesoderm and inhibits growth of the embryonic heart. It is not known which developmental processes are perturbed by sodium channel knockdown and whether reduced cell number is from impaired migration of cardiac progenitors into the heart, impaired myocyte proliferation, or both. We found that embryos deficient in scn5Lab displayed defects in primary cardiogenesis specific to loss of nkx2.5, but not nkx2.7. We generated kaede reporter fish and demonstrated that embryos treated with anti-scn5Lab morpholino showed normal secondary differentiation of cardiomyocytes at the arterial pole between 30 and 48 h post-fertilization. However, while proliferating myocytes were readily detected at 48 hpf in wild type embryos, there were no BrdU-positive cardiomyocytes in embryos subjected to anti-scn5Lab treatment. Proliferating myocytes were present in embryos injected with anti-tnnt2 morpholino to phenocopy the silent heart mutation, and absent in embryos injected with anti-tnnt2 and anti-scn5Lab morpholinos, indicating cardiac contraction is not required for the loss of proliferation. These data demonstrate that the role of scn5Lab in later heart growth does not involve contribution of the secondary heart field, but rather proliferation of cardiomyocytes, and appears unrelated to the role of the channel in cardiac electrogenesis.

Photonic band structures of periodic arrays of pores in a metallic host: tight-binding beyond the quasistatic approximation.

We have calculated the photonic band structures of metallic inverse opals and of periodic linear chains of spherical pores in a metallic host, below a plasma frequency ωp. In both cases, we use a tight-binding approximation, assuming a Drude dielectric function for the metallic component, but without making the quasistatic approximation. The tight-binding modes are linear combinations of the single-cavity transverse magnetic (TM) modes. For the inverse-opal structures, the lowest modes are analogous to those constructed from the three degenerate atomic p-states in fcc crystals. For the linear chains, in the limit of small spheres compared to a wavelength, the results bear some qualitative resemblance to the dispersion relation for metal spheres in an insulating host, as calculated by Brongersma et al. [Phys. Rev. B 62, R16356 (2000)]. Because the electromagnetic fields of these modes decay exponentially in the metal, there are no radiative losses, in contrast to the case of arrays of metallic spheres in air. We suggest that this tight-binding approach to photonic band structures of such metallic inverse materials may be a useful approach for studying photonic crystals containing metallic components, even beyond the quasistatic approximation.

Experimental demonstration of scanned spin-precession microscopy.

We present a new tool for imaging spin properties. We show that a spatially averaged spin signal, measured as a function of a scanned magnetic probe's position, contains information about the local spin properties. In this first demonstration we map the injected spin density in GaAs by measuring spin photoluminescence with a resolution of 1.2 µm. The ultimate limit of the technique is set by the gradient of the probe's field, allowing for a resolution beyond the optical diffraction limit. Such probes can also be integrated with other detection methods. This generality allows the technique to be extended to buried interfaces and optically inactive materials.

Walkie talkies cause more electromagnetic interference to medical equipment than mobile phones.

It is generally realised that mobile phones can interfere with medical electrical equipment and many hospitals have policies which aim to minimise the risk to their patients from this cause. Walkie talkies are also used in hospitals, but very little information is available concerning their ability to interfere with hospital equipment. Two walkie talkies and three mobile phones have been used to study and compare interference in 29 items of patient-connected equipment in a large hospital. Test results show that with some equipment there will be signal distortion and/or false alarms, and a Power off/on Reset may be necessary. In rare cases, when equipment is subjected to extreme signal strengths, it is possible to observe equipment failure requiring the replacement of failed components. For these tests the walkie talkies were set at 4W of output power and they caused significantly more interference than the mobile phones. The observed effects have been classified according to the maximum distance at which they were observed and according to the criticality of the possible outcome for the patient. It is concluded that, except for emergency services, the use of walkie talkies should be restricted in hospital buildings.

Multiple brain metastases are associated with poor survival in patients treated with surgery and radiotherapy.

PURPOSE: A retrospective analysis was performed to evaluate the role of surgery in the management of patients with solitary and multiple brain metastases. PATIENTS AND METHODS: Between 1980 and 1990, 46 patients underwent surgical resection of brain metastases at the University of Colorado Health Sciences Center. All but two patients received postoperative whole-brain radiotherapy to a median total dose of 30 Gy (range, 11.4 Gy to 50.0 Gy). Lung was the most common (56%) primary site and adenocarcinoma was the most common (46%) tumor histology. Twenty-eight of 46 patients (61%) had solitary metastases, while the remaining 18 patients had two or more foci. RESULTS: The median survival of all 46 patients was 11 months, and the 1- and 2-year survival rates were 40% and 12%, respectively. Moderately severe to severe neurologic impairment at the time of diagnosis and the presence of multiple brain metastases were associated with a significantly poorer survival. In patients with solitary metastasis, gross total resection and adenocarcinoma tumor histology significantly prolonged survival, whereas primary tumor site, the presence of active extracranial disease, and radiation dose had no significant effect on survival. CONCLUSION: These results are consistent with a recent randomized study supporting the role of surgery and whole-brain radiation therapy in the management of patients with solitary brain metastases. We would caution against the generalization of this concept to patients with two or more brain metastases.

Synchronization in disordered Josephson junction arrays: small-world connections and the Kuramoto model.

We study synchronization in disordered arrays of Josephson junctions. In the first half of the paper, we consider the relation between the coupled resistively and capacitively shunted junction (RCSJ) equations for such arrays and effective phase models of the Winfree type. We describe a multiple-time-scale analysis of the RCSJ equations for a ladder array of junctions with non-negligible capacitance in which we arrive at a second order phase model that captures well the synchronization physics of the RCSJ equations for that geometry. In the second half of the paper, motivated by recent work on small-world networks, we study the effect on synchronization of random, long-range connections between pairs of junctions. We consider the effects of such shortcuts on ladder arrays, finding that the shortcuts make it easier for the array of junctions in the nonzero voltage state to synchronize. In two-dimensional (2D) arrays we find that the additional shortcut junctions are only marginally effective at inducing synchronization of the active junctions. The differences in the effects of shortcut junctions in 1D and 2D can be partly understood in terms of an effective phase model.

Comparison of total body chlorine, potassium, and water measurements in children with cystic fibrosis.

BACKGROUND: Symptoms of cystic fibrosis (CF) may limit the utility of total body chlorine (TBCl) and total body potassium (TBK) measurements for assessing body fluid compartments of children. OBJECTIVE: This study assessed relations among independent measurements of TBCl, TBK, and total body water (TBW) in children with CF. DESIGN: We compared cross-sectional measurements of TBCl by in vivo neutron activation analysis, TBK by whole-body counting of (40)K, TBW by D(2)O dilution [TBW(D(2)O)], and TBW from TBCl and TBK [TBW(Cl + K)] in 19 prepubertal children (13 boys) aged 7.6-12.5 y who had mild symptoms of CF. Body-composition measurements were compared with data from previous studies of healthy children. RESULTS: Subjects with CF had deficits in TBCl, TBK, TBW, and body weight compared with control reference data (P < 0.05). The ratios (TBCl + TBK)/TBW and TBCl/TBK were not significantly different from control reference values, and plasma chlorine and potassium concentrations were within control reference ranges. The sum of TBCl and TBK correlated with TBW(D(2)O) (r(2) = 0.79, P < 0.001), and TBW(Cl + K) correlated with TBW(D(2)O) (r(2) = 0.78, P < 0.001). TBW(Cl + K) was similar to TBW(D(2)O) (mean +/- SEM: 19.0 +/- 0.5 compared with 19.4 +/- 0.5 L; NS). CONCLUSIONS: Prepubertal children with mild symptoms of CF can develop deficits in TBCl, TBK, and TBW that reflect chronic energy malnutrition. Mild symptoms of CF do not appear to affect normal relations among TBCl, TBK, and TBW. Measurements of TBCl and TBK may be used to assess body fluid compartments in these patients.

Prostatic thermoluminescent dosimeter analysis in a patient treated with 18 MV X rays through a prosthetic hip.

External beam radiation therapy with high energy photon beams through hip prostheses has been shown to cause dose inhomogeneities for target volumes in the pelvis. In this work, measurements of dose using thermoluminescent dosimetry were compared with dose calculations from a computerized treatment planning system in a patient with prostatic carcinoma and a cobalt-chromium-molybdenum hip prosthesis. A 39% decrement in dose at isocenter was demonstrated for an 18 MV photon beam passing through the prosthesis. A discrepancy of only 3.1% was shown between measured and calculated dose when the tissue-maximum ratio (TMR) method of heterogeneity correction was used. However, it is recognized that several sources of error are possible when heterogeneity corrections are performed for high density prostheses and these are discussed below. The results of this work stress the importance of accurate data for use with the "ratio of TMR's" algorithm in order that accurate treatment planning can be performed.

Total body dual X-ray absorptiometry is a good measure of both fat mass and fat-free mass in liver cirrhosis compared to "gold-standard" techniques. Melbourne Liver Group.

Liver cirrhosis is a condition in which overnutrition, edema, and undernutrition can coexist simultaneously, or successively, over a period of time, giving rise to alterations in body composition, as well as systemic and multiorgan manifestations. We undertook a cross-sectional study of body composition in 198 adult patients with liver cirrhosis (140 males, mean age 53.6, range 31-85 years; and 58 females, mean age 58.4, range 36-79 years). The patients had cirrhosis of differing etiology and different stages of severity. They were gathered from seven different hospital clinics in the city of Melbourne, Australia, but all the body composition measurements were performed in one body composition laboratory. A variety of body composition techniques were used to identify which commonly available ones could best assess both fat-free mass and fat mass relative to a criterion "gold-standard" method available in a specialist laboratory. A gold-standard fat-free mass (FFMGS) was defined as the sum of total body protein, measured by in vivo neutron activation analysis (IVNA), plus total body water, measured by D2O dilution, plus bone mineral content, measured by dual X-ray absorptiometry (DXA). A gold-standard fat mass (FATGS) was defined as the difference between body weight and FFMGS. "Usual" fat mass and fat-free mass were defined by different techniques including DXA, anthropometry (ANT), single-frequency bioelectrical impedance (SFBIA), multiple-frequency bioelectrical impedance spectroscopy (MFBIA), and whole body gamma counting (TBK). The FFMGS was overhydrated in both sexes, relative to the usual value of 0.73, but women were significantly overhydrated compared to men. Relative to the gold-standard deuterium oxide dilution method for measuring total body water, SFBIA slightly overestimated TBW, whereas MFBIA slightly underestimated TBW, with both methods having wide limits of agreement for any single estimate. In comparing FFM to FFMGS, only DXA showed a small negative bias, in both males and females, with modest limits of agreement for any single estimate. All other methods showed a large negative bias (ANT, SFBIA, and MFBIA) or a large positive bias (TBK) relative to FFMGS, with wide limits of agreement. In comparing FAT with the FATGS, only DXA showed a small positive bias, in both males and females, with modest limits of agreement for any single estimate. All other methods showed a large positive bias (ANT, SFBIA, and MFBIA) or a large negative bias (TBK) relative to FATGS, with wide limits of agreement. In cirrhosis, DXA is a good and widely available method to assess both fat mass and fat-free mass. However, it cannot give information about the quality of the FFM, particularly its water content. The bedside methods of anthropometry and bioelectrical impedance, both SFBIA and MFBIA, are poor methods of measuring body composition in patients with liver cirrhosis, whereas whole body gamma counting, although not widely available, also significantly differs from the gold-standard method of assessment of fat-free mass and fat mass in liver cirrhosis.

The use of Cole-Cole plots to compare two multifrequency bioimpedance instruments.

Two commercially available multifrequency bioimpedance spectrometers (Xitron 4000B and SEAC SFB3) were compared by performing measurements on a set of electronic circuits and by studying 14 healthy volunteers. Output data were plotted as reactance versus resistance and fitted with a semi-circle using a least squares fitting program. In tests with six electronic circuits both instruments produced impedance loci that were well described by semicircular Cole-Cole plots, though there were some minor discrepancies using the Xitron instrument at frequencies above 150 kHz. When tested on the volunteers the SEAC instrument gave very good fits (RMSE = 1.5 Omega) to a semi-circle from 5-600 kHz on all volunteers. The Xitron instrument gave excellent fits to the semi-circle between 5 and 55 kHz (RMSE = 0.7 Omega) but above 55 kHz the phase measurements stayed constant or even increased, confirming the anomalous behaviour reported by other authors. The conclusions to be drawn are that the semicircular plots predicted by the Cole-Cole theory give a very good description of multifrequency impedance data recorded by the SEAC SFB3 instrument, on human subjects, for frequencies between 5 and 600 kHz. The Xitron 4000B is not able to reproduce the theoretically expected results in humans above 55 kHz.

Improvement of Lesion Detection in Scintigraphic Images by SVD Techniques for Resolution Recovery.

The properties of singular value decomposition (SVD) are used to implement an SVD spatial domain pseudoinverse restoration filter. This type of filter is attractive for poor imaging conditions (low spatial resolution, high image noise) and is thus appealing for nuclear medicine images. The method might offer some advantages over more traditional frequency domain filter techniques since the restoration is performed on a local rather than global basis. High-contrast thyroid phantom images collected at different count densities and low-contrast liver phantom images were processed with the SVD filter. Restored images yielded improved spatial resolution, lesion contrast, and signal-to-noise ratio. The SVD pseudoinverse restoration filter implemented as an interactive process permits the operator to terminate filtering at a stage where the visually "best" image is obtained compared to the original data. Processed images suggest that the technique may have potential for improving lesion detection in nuclear medicine.

Total body protein status assessed by different estimates of fat-free mass in adult peritoneal dialysis patients.

OBJECTIVE: To assess the usefulness of fat-free mass (FFM) as an index of total body protein (TBPr) status in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: TBPr was measured by in vivo neutron activation analysis (IVNAA) and expressed as a standardised protein index (PI). FFM was estimated by dual energy X-ray absorptiometry (DXA), whole body counting of total body potassium (TBK), and creatinine kinetics (CK), and expressed as a standardised FFM index (FFMI). FFM was also determined by a criterion method based on four compartment model (4CM) which is defined as the sum of total body water determined by D2O dilution, TBPr determined by IVNAA, bone mineral determined by DXA, and glycogen estimated to be 4.4% of TBPr. Each patient was measured within a four hour period by all methods. SETTING: Body Composition Laboratory, Monash Medical Centre. SUBJECTS: Six male and twelve female CAPD patients (33-77 years). RESULTS: FFMI assessed by DXA and by TBK agreed with measurements of PI on identifying the mean TBPr status of the CAPD group as significantly below a comparable normal reference population (mean Z score: PI = -1.01 (P < 0.05); FFMI by DXA = -0.50 (P < 0.05); FFMI by TBK = -1.24 (P < 0.05)). In contrast, FFMI assessed by CK did not reveal a significantly reduced TBPr status (mean Z score: -0.70 (NS)). Furthermore, significant linear correlations were noted between PI and FFMI estimated by DXA and by TBK (r = 0.57 (P < 0.05) vs r = 0.69 (P < 0.05)) however no significant correlation was observed between PI and FFMI estimated by CK (r = 0.36 (NS)). Moderate variation in FFM hydration did not compromise the ability of DXA, TBK or CK to differentiate between protein deleted, normal and enriched patients. Comparison of FFM estimates between the criterion method and either DXA, TBK or CK revealed no significant bias (+ 1.8 kg vs -2.0 kg vs +0.8 kg) and respective SEE values of 3.8 kg (8.3%), 5.9 kg (14.3%) and 9.6 kg (21.7%). CONCLUSION: The findings of this study indicate that FFM estimated by either DXA or the whole body counting of TBK is a useful index of TBPr status in CAPD patients. However, FFM assessed by CK does not appear to be an appropriate index of TBPr status in CAPD patients.

Body composition changes following laparoscopic gastric banding for morbid obesity.

Most reports of outcome following obesity surgery report weight and co-morbidity changes only. We studied body composition changes in 17 adult patients (15 F, 2 M, age 43+/-2 years, range 28-58 years), with morbid obesity (initial BMI 40.4+/-4.9 kg/m(2), range 34.7-48.8) who were managed surgically by laparoscopically inserting an adjustable gastric band. Body composition was studied before and after surgery (mean interval of 909+/-51 days, range 441-1155 days) using anthropometry (abdominal circumference, AC, sum of four skinfold thicknesses, SFSUM), whole-body potassium counting (TBK), in vivo neutron activation analysis total body nitrogen (TBProtein) and whole-body dual-energy ray absorptiometry (total body percent fat TBF%, and total body bone mineral density TBBMD). Weight loss over the study period was 23.4+/-2.5 kg. ( p<0.0003) with an AC reduction of 20.0+/-4.5 cm ( p<0.008). Both SFSUM and TBF% were significantly reduced ( p<0.02 and p<0.0005 respectively). Both TBK and TBProtein after normalization for sex and height, were significantly ( p<0.0054 and p<0.001 respectively) reduced, but the ratio of loss of fat mass to fat-free mass, at 4.4:1 was usual for weight loss, and there was no significant changes in the ratio of potassium to protein. TBBMD, after normalization relative to a young same sex adult, was not significantly changed. In this group of patients, most of the substantial weight loss over a 2- to 3-year period was due to loss of fat mass, with relatively less reduction in the components of fat-free mass. Adjustable laparoscopic gastric banding induces fat loss without significant other deleterious effects on body composition.

Scaling properties of random walks on small-world networks.

Using both numerical simulations and scaling arguments, we study the behavior of a random walker on a one-dimensional small-world network. For the properties we study, we find that the random walk obeys a characteristic scaling form. These properties include the average number of distinct sites visited by the random walker, the mean-square displacement of the walker, and the distribution of first-return times. The scaling form has three characteristic time regimes. At short times, the walker does not see the small-world shortcuts and effectively probes an ordinary Euclidean network in d dimensions. At intermediate times, the properties of the walker shows scaling behavior characteristic of an infinite small-world network. Finally, at long times, the finite size of the network becomes important, and many of the properties of the walker saturate. We propose general analytical forms for the scaling properties in all three regimes, and show that these analytical forms are consistent with our numerical simulations.

Criminal investigation of child sexual abuse: a comparison of cases referred to the prosecutor to those not referred.

OBJECTIVE: The present study sought to identify characteristics of child sexual abuse cases which differentiate cases referred for criminal prosecution ("criminal-action") from those not referred ("dropped") by investigators. METHOD: The study sample consisted of 1043 children who completed a forensic interview for sexual abuse that allegedly occurred at the hands of an adult between January 1, 1993 and December 31, 1996 in Bernalillo County of New Mexico. Data was systematically obtained from forensic interview files and offender records at the local prosecutor's office. RESULTS: Differences between criminal-action and dropped cases were found in relation to the children (age, sex and ethnicity), the alleged offenders (age, sex and relationship to child), and the case characteristics (disclosure and injury to the child). CONCLUSIONS: The present study provided insight into the characteristics of a previously ignored population (reported child sexual abuse cases that are not referred for prosecution). Recommendations are made to address the needs of these children and their families.

Spatial sensitivity measurements of a prompt gamma IVNAA facility.

A technique has been developed for measuring the spatial sensitivity of a prompt gamma in vivo neutron activation analysis facility as used for determining total body nitrogen (i.e. protein). A water filled perspex phantom was used to simulate a patient. Relative spatial sensitivity of the system was measured at various positions in the tank by observing the prompt gamma rays from thermal neutron capture in the 35Cl of a carbon tetrachloride sample contained in a small glass phial.

A neutron activation analysis facility for in vivo measurement of nitrogen and chlorine in children.

The construction, calibration and evaluation of a prompt- gamma in vivo neutron activation analysis (IVNAA) facility for the simultaneous measurement of total body nitrogen (TBN) and chlorine (TBCl) in children is described. Subjects are irradiated unilaterally by a 0.2 GBq 252Cf neutron source from shoulder to mid thigh in both supine and prone positions. Prompt gamma-ray spectra are measured with two pairs of NaI(TI) crystals (each crystal: 10 cm x 10 cm x 15 cm) positioned on both sides of the subject. TBN and TBCl are estimated from the ratios of nitrogen-to-hydrogen (Nc/Hc) and chlorine-to-hydrogen (Clc/Hc) counts as determined from the measurement of 10.83 MeV, 8.57 MeV and 2.22 MeV prompt gamma-rays from the respective reactions 14N(n, gamma)15N, 36Cl(n, gamma)35Cl, and 1H(n, gamma)D. Nc/Hc and Clc/Hc are corrected for the effect of body width and thickness on background and gamma-ray attenuation. Total body hydrogen (TBH) is used as an internal standard which is independently determined using a four compartment model of body weight defined as the sum of total body water (TBW) measured by the D2O dilution technique, total body protein (TBPr) (i.e. 6.25 x TBN) measured by IVNAA, total body bone mineral (TBBM) measured by dual energy x-ray absorptiometry and total body fat (TBF) estimated as body weight less the sum of TBW, TBPr and TBBM. The effective dose equivalent to a small child is 0.25 mSv (Q = 20) per measurement scan. Repeated measurements of a child-size bottle phantom containing tissue-equivalent concentrations of nitrogen and chlorine yield respective intra- and inter-assay precision values of 2.8% (CV) and 2.3% for TBN measurements, and 7.9% and 10.0% for TBCl measurements. Similarly, intra- and inter-assay accuracy is determined to be respectively +0.1% +/- 1.0% (mean, 95% confidence interval) and +1.4% +/- 1.4% for TBN measurements, and +2.3% +/- 4.3% and +3.9% +/- 6.0% for TBCl measurements.

Mobile telephones interfere with medical electrical equipment.

Electromagnetic interference in medical electrical equipment has not been a serious problem in recent years even with the proliferation of analogue mobile phones and two-way handheld radios. With the introduction of GSM digital mobile phones into Australia we have conducted measurements and found that, within 2m, the electric fields from digital mobile phones can exceed the immunity level of 7 V/m recommended by the US Food and Drug Administration (FDA) for medical electrical equipment. Current analogue mobile phones were shown to produce electric fields that exceed the 7 V/m level only at relatively shorter distances. In another test, both analogue and digital mobile phones were operated close to a range of typical medical electrical equipment. It was found that existing equipment generally meets the FDA standard, but digital mobile phones caused a variety of artefacts and alarm conditions. This problem must be addressed by the medical engineering profession; in the meantime, nursing and other staff should be educated to recognise these problems and restrictions must be placed upon the use of mobile phones in hospitals.

Bax targets mitochondria by distinct mechanisms before or during apoptotic cell death: a requirement for VDAC2 or Bak for efficient Bax apoptotic function.

In non-apoptotic cells, Bak constitutively resides in the mitochondrial outer membrane. In contrast, Bax is in a dynamic equilibrium between the cytosol and mitochondria, and is commonly predominant in the cytosol. In response to an apoptotic stimulus, Bax and Bak change conformation, leading to Bax accumulation at mitochondria and Bak/Bax oligomerization to form a pore in the mitochondrial outer membrane that is responsible for cell death. Using blue native-PAGE to investigate how Bax oligomerizes in the mitochondrial outer membrane, we observed that, like Bak, a proportion of Bax that constitutively resides at mitochondria associates with voltage-dependent anion channel (VDAC)2 prior to an apoptotic stimulus. During apoptosis, Bax dissociates from VDAC2 and homo-oligomerizes to form high molecular weight oligomers. In cells that lack VDAC2, constitutive mitochondrial localization of Bax and Bak was impaired, suggesting that VDAC2 has a role in Bax and Bak import to, or stability at, the mitochondrial outer membrane. However, following an apoptotic stimulus, Bak and Bax retained the ability to accumulate at VDAC2-deficient mitochondria and to mediate cell death. Silencing of Bak in VDAC2-deficient cells indicated that Bax required either VDAC2 or Bak in order to translocate to and oligomerize at the mitochondrial outer membrane to efficiently mediate apoptosis. In contrast, efficient Bak homo-oligomerization at the mitochondrial outer membrane and its pro-apoptotic function required neither VDAC2 nor Bax. Even a C-terminal mutant of Bax (S184L) that localizes to mitochondria did not constitutively target mitochondria deficient in VDAC2, but was recruited to mitochondria following an apoptotic stimulus dependent on Bak or upon over-expression of Bcl-xL. Together, our data suggest that Bax localizes to the mitochondrial outer membrane via alternate mechanisms, either constitutively via an interaction with VDAC2 or after activation via interaction with Bcl-2 family proteins.