InGaN islands and thin films grown on epitaxial graphene.

In this work, the growth of InGaN on epitaxial graphene by molecular beam epitaxy is studied. The nucleation of the alloy follows a three-dimensional (3D) growth mode in the observed temperature range of 515 °C-765 °C, leading to the formation of dendrite-like islands. Careful Raman scattering experiments show that the graphene underneath is not degraded by the InGaN growth. Moreover, lateral displacement of the nuclei during an atomic force microscopy (AFM) scan demonstrates weak bonding interactions between the InGaN and the graphene. Finally, a longer growth time of the alloy gives rise to a compact thin film in a partial epitaxial relationship with the SiC underneath the graphene.

The extreme light infrastructure-nuclear physics (ELI-NP) facility: new horizons in physics with 10 PW ultra-intense lasers and 20 MeV brilliant gamma beams.

The European Strategy Forum on Research Infrastructures (ESFRI) has selected in 2006 a proposal based on ultra-intense laser fields with intensities reaching up to 1022-1023 W cm-2 called 'ELI' for Extreme Light Infrastructure. The construction of a large-scale laser-centred, distributed pan-European research infrastructure, involving beyond the state-of-the-art ultra-short and ultra-intense laser technologies, received the approval for funding in 2011-2012. The three pillars of the ELI facility are being built in Czech Republic, Hungary and Romania. The Romanian pillar is ELI-Nuclear Physics (ELI-NP). The new facility is intended to serve a broad national, European and International science community. Its mission covers scientific research at the frontier of knowledge involving two domains. The first one is laser-driven experiments related to nuclear physics, strong-field quantum electrodynamics and associated vacuum effects. The second is based on a Compton backscattering high-brilliance and intense low-energy gamma beam (<20 MeV), a marriage of laser and accelerator technology which will allow us to investigate nuclear structure and reactions as well as nuclear astrophysics with unprecedented resolution and accuracy. In addition to fundamental themes, a large number of applications with significant societal impact are being developed. The ELI-NP research centre will be located in Magurele near Bucharest, Romania. The project is implemented by 'Horia Hulubei' National Institute for Physics and Nuclear Engineering (IFIN-HH). The project started in January 2013 and the new facility will be fully operational by the end of 2019. After a short introduction to multi-PW lasers and multi-MeV brilliant gamma beam scientific and technical description of the future ELI-NP facility as well as the present status of its implementation of ELI-NP, will be presented. The science and examples of societal applications at reach with these electromagnetic probes with much improved performances provided at this new facility will be discussed with a special focus on day-one experiments and associated novel instrumentation.

HYDROCEPHALY, SCHIZENCEPHALY, SPONDYLOCOSTAL DYSPLASIA, AND HYPOPARATHYROIDISM IN AN INFANT OF A DIABETIC MOTHER.

CONTEXT: Diabetes mellitus is the most frequent chronic complication in pregnancy and continues to contribute to increased perinatal morbidity and mortality in newborns. Macrosomia, respiratory distress syndrome, metabolic and electrolytic disturbances, and increased rates of congenital structural defects are well-known neonatal complications associated with maternal diabetes, even if well-controlled. CASE REPORT: A macrosomic infant born from an insulin-dependent mother, with uncontrolled diabetes and lack of adequate prenatal care, prenatally diagnosed with hydrocephaly showed a complicated postnatal course. Initial respiratory distress syndrome and transient hypoglycemia, rapidly corrected under treatment, were followed by persistent hypocalcemia and hyperphosphatemia due to hypoparathyroidism and evolving hydrocephaly. Ventriculoperitoneal shunting was followed by resolution of hypocalcemia, but seizures associated with schizencephaly and recurrent respiratory tract infections, aggravated by spondylocostal dysplasia, concurred to infant's demise at the age of 5 months. CONCLUSIONS: The reported case is rare due to multiple aspects: persistent hypoparathyroidism, uncommon association of schizencephaly, and even rarely association with spondylocostal dysplasia, all these conditions requiring a multidisciplinary therapeutic approach. Also, the reported case is evocative for challenges associated with infants born from diabetic mothers.

THE ROLE OF ESTROGENS AND ESTROGEN RECEPTORS IN MELANOMA DEVELOPMENT AND PROGRESSION.

Melanoma has a significant mortality and its growing incidence is associated with important social and health care costs. Thus, investigation of the complex mechanisms contributing to emergence and development of melanoma are of real interest both in scientific research and clinical practice. Estrogens play an important role in the emergence and development of certain types of cancer, such as breast cancer, endometrial cancer and ovarian cancer, but their role in development of cutaneous melanoma is still a matter of debate. Various data suggest that increased levels of endogenous estrogens during pregnancy or exposure to exogenous estrogens by use of oral contraceptives (OCs) and hormone replacement therapy (HRT) may have a potential role in melanoma development and progression. Moreover, there were revealed several intracellular pathways which can support the connection between estrogens, estrogen receptors (ER) and melanoma. While ER-ß plays an antiproliferative role, ER-α promotes cell growth and cellular atypia. Thus, inhibition of ER-ß activity in the skin can increase the risk for development of cutaneous melanoma and spread of metastatic cells. However, despite recent advances in this area, the exact role and clinical implications of estrogens and estrogen receptors in melanoma are still not entirely understood and require further investigations.

Constraint of the astrophysical

The Galactic 1.809-MeV γ-ray signature from the ß decay of ^{26g}Al is a dominant target of γ-ray astronomy, of which a significant component is understood to originate from massive stars. The ^{26g}Al(p,γ)^{27}Si reaction is a major destruction pathway for ^{26g}Al at stellar temperatures, but the reaction rate is poorly constrained due to uncertainties in the strengths of low-lying resonances in ^{27}Si. The ^{26g}Al(d,p)^{27}Al reaction has been employed in inverse kinematics to determine the spectroscopic factors, and hence resonance strengths, of proton resonances in ^{27}Si via mirror symmetry. The strength of the 127-keV resonance is found to be a factor of 4 higher than the previously adopted upper limit, and the upper limit for the 68-keV resonance has been reduced by an order of magnitude, considerably constraining the ^{26g}Al destruction rate at stellar temperatures.

Characterization and Modeling of Ply/Tool and Ply/Ply Slippage Phenomena of Unidirectional Polycarbonate CF Tapes.

Thermoplastic tapes are commonly processed by the rapid and efficient stamp forming process. During this forming process, the individual unidirectional tapes of the composite stack move relative to each other and relative to the surface of the tool while being in contact with the corresponding counterpart. As a result, the material exhibits a certain resistance against this movement, which is generally dependent on velocity, normal pressure, and temperature. Therefore, this work investigates the ply/tool and ply/ply slippage of unidirectional, carbon fiber reinforced polycarbonate tapes and provides an alternative implementation of the experimentally observed slippage using cohesive zone modeling. The backbone of the modeling approach is an experimental data set obtained from pull-through experiments. In comparison to common slippage or friction theories, the force plateau of thermoplastic UD tapes at elevated temperatures is observed after an initial force peak has been overcome. For both configurations, ply/tool and ply/ply, a reduction of the initial force peak was observed for increasing temperature. Furthermore, the resulting plateau force value is at least 36% higher in the ply/ply configuration compared to the ply/tool configuration at 200 °C. The derived cohesive zone model allows for accurate modeling of the initial force peak and the plateau.

Lactate MRSI and DCE MRI as surrogate markers of prostate tumor aggressiveness.

Longitudinal studies of lactate MRSI and dynamic contrast-enhanced MRI were performed at 4.7 T in two prostate tumor models grown in rats, Dunning R3327-AT (AT) and Dunning R3327-H (H), to determine the potential of lactate and the perfusion/permeability parameter Ak(ep) as markers of tumor aggressiveness. Subcutaneous AT (n = 12) and H (n = 6) tumors were studied at different volumes between 100 and 2900 mm(3) (Groups 1-5). Lactate concentration was determined using selective multiple quantum coherence MRSI with the phantom substitution method. Tumor enhancement after the administration of gadolinium diethylenetriaminepenta-acetic acid was analyzed using the Brix-Hoffmann model and the Ak(ep) parameter was used as a measure of tumor perfusion/permeability. Lactate was not detected in the smallest AT tumors (Group 1; 100-270 mm(3) ). In larger AT tumors, the lactate concentration increased from 2.8 ± 1.0 mm (Group 2; 290-700 mm(3)) to 8.4 ± 2.9 mm (Group 3; 1000-1340 mm(3)) and 8.2 ± 2.2 mm (Group 4; 1380-1750 mm(3) ), and then decreased to 5.0 ± 1.7 mm (Group 5; 1900-2500 mm(3)), and was consistently higher in the tumor core than in the rim. Lactate was not detected in any of the H tumors. The mean tumor Ak(ep) values decreased with increasing volume in both tumor types, but were significantly higher in H tumors. In AT tumors, the Ak(ep) values were significantly higher in the rim than in the core. Histological hypoxic and necrotic fractions in AT tumors increased with volume from 0% in Group 1 to about 20% and 30%, respectively, in Group 5. Minimal amounts of hypoxia and necrosis were found in H tumors of all sizes. Thus, the presence of lactate and heterogeneous perfusion/permeability are signatures of aggressive, metabolically deprived tumors.

Neutron single particle structure in 131Sn and direct neutron capture cross sections.

Recent calculations suggest that the rate of neutron capture by (130)Sn has a significant impact on late-time nucleosynthesis in the r process. Direct capture into low-lying bound states is expected to be significant in neutron capture near the N=82 closed shell, so r-process reaction rates may be strongly impacted by the properties of neutron single particle states in this region. In order to investigate these properties, the (d,p) reaction has been studied in inverse kinematics using a 630 MeV beam of (130)Sn (4.8 MeV/u) and a (CD(2))(n) target. An array of Si strip detectors, including the Silicon Detector Array and an early implementation of the Oak Ridge Rutgers University Barrel Array, was used to detect reaction products. Results for the (130)Sn(d, p)(131)Sn reaction are found to be very similar to those from the previously reported (132)Sn(d, p)(133)Sn reaction. Direct-semidirect (n,γ) cross section calculations, based for the first time on experimental data, are presented. The uncertainties in these cross sections are thus reduced by orders of magnitude from previous estimates.

Halo nucleus 11Be: a spectroscopic study via neutron transfer.

The best examples of halo nuclei, exotic systems with a diffuse nuclear cloud surrounding a tightly bound core, are found in the light, neutron-rich region, where the halo neutrons experience only weak binding and a weak, or no, potential barrier. Modern direct-reaction measurement techniques provide powerful probes of the structure of exotic nuclei. Despite more than four decades of these studies on the benchmark one-neutron halo nucleus 11Be, the spectroscopic factors for the two bound states remain poorly constrained. In the present work, the 10Be(d,​p) reaction has been used in inverse kinematics at four beam energies to study the structure of 11Be. The spectroscopic factors extracted using the adiabatic model were found to be consistent across the four measurements and were largely insensitive to the optical potential used. The extracted spectroscopic factor for a neutron in an nℓj=2s(1/2) state coupled to the ground state of 10Be is 0.71(5). For the first excited state at 0.32 MeV, a spectroscopic factor of 0.62(4) is found for the halo neutron in a 1p(1/2) state.

Characterization of a plutonium-beryllium neutron source.

Here we present an investigation of a plutonium-beryllium neutron source available at the Horia Hulubei National Institute of Physics and Nuclear Engineering, Romania, to be used for detector characterization during the implementation of the Extreme Light Infrastructure - Nuclear Physics project. Using several different techniques and instruments, we have measured the isotopic composition for plutonium to be 75% 239Pu and 24% 240Pu, with a minor contribution from other isotopes. Furthermore, we have measured the source activity as of November 20th 2019 to be 2.220(5)×105 neutrons per second with a mean energy of 3.25(17) MeV. We have also measured both the γ-tagged and full neutron energy spectra, and discuss the origin of the observed structure in the neutron energies based on these. All these parameters are of importance both for traceability of nuclear material, radioprotection, and accurate detector characterization.

[Multiple splenic abscesses associated with normotensive hydrocephaly]. / Abcese splenice multiple asociate cu hidrocefalia adultului.

The paper contains a concise review of the current literature on the splenic abscesses and presents an unusual association of multiple splenic abscesses with normotensive hydrocephaly to an elderly patient, treated by ventriculo-cardiac shunting and splenectomy as an one stage procedure performed by a combined surgical team (neurosurgeon, vascular surgeon and general surgeon), with a favourable outcome. As far as the authors know, this is the first communication of multiple splenic abscesses associated with adult hydrocephaly treated by a simultaneous surgical approach.

Electromagnetic character of the competitive γγ/γ-decay from 137mBa.

Second-order processes in physics is a research topic focusing attention from several fields worldwide including, for example, non-linear quantum electrodynamics with high-power lasers, neutrinoless double-ß decay, and stimulated atomic two-photon transitions. For the electromagnetic nuclear interaction, the observation of the competitive double-γ decay from 137mBa has opened up the nuclear structure field for detailed investigation of second-order processes through the manifestation of off-diagonal nuclear polarisability. Here, we confirm this observation with an 8.7σ significance, and an improved value on the double-photon versus single-photon branching ratio as 2.62 × 10-6(30). Our results, however, contradict the conclusions from the original experiment, where the decay was interpreted to be dominated by a quadrupole-quadrupole component. Here, we find a substantial enhancement in the energy distribution consistent with a dominating octupole-dipole character and a rather small quadrupole-quadrupole component in the decay, hindered due to an evolution of the internal nuclear structure. The implied strongly hindered double-photon branching in 137mBa opens up the possibility of the double-photon branching as a feasible tool for nuclear-structure studies on off-diagonal polarisability in nuclei where this hindrance is not present.

99mTc-HMPAO labelled white blood cell scintigraphy in patients with osteoarticular infection: the value of late images for diagnostic accuracy and interobserver reproducibility.

The objectives of this study were to evaluate the diagnostic value of 99mTc-HMPAO labelled white blood cell scintigraphy (WBCS) in patients with suspected osteomyelitis using late images and to study interobserver reproducibility. This study prospectively included 120 patients, and after a follow-up of one year, only 70 patients (n = 49 with implants, n = 21 without implants) were selected. The final diagnosis of infection was based either on microbiological data (n = 54) or follow-up (n = 16). We performed WBCS with 4 h and 24 h scans. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 77%, 72%, 83%, 64%, and 75% at 4 h, and 74%, 87%, 91%, 59%, and 79% at 24 h, respectively. The interobserver reproducibility shows a 63% prevalence of agreement between results (kappa = 0.5) at 4 h and 80% (kappa = 0.74) at 24 h, respectively. WBCS with 24-h images improves specificity and interobserver reproducibility in patients with suspected osteoarticular sepsis.

Aspects of communication in medical life. Doctor-patient communication: differentiation and customization.

One of the weaknesses of the Romanian medical system is the absence of the communicational culture. This absence is felt at all levels of the healthcare system: doctor-patient relationship, doctor-patient's relatives relationship, labor relations within the medical teams and units, the management of the large hospitals and of the medical institutions from the public administration system and last, but not least, the relationships of these units and institutions with the public opinion and, particularly, with the stakeholders. This paper tackled with some of the principles and values that underlie an efficient communication, the default of which was felt in various domains of the Romanian medical life. They were analyzed from the perspective of the Romanian and international literature and the conclusions drawn might inspire proposals for the improvement of the medical education as well as for the professional development of the Romanian doctors.

RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-gamma.

Two aspects of cytokine therapy of intracerebral tumors are considered in this study: modulation of tumor growth in vivo and central nervous system toxicity. Coimplantation of RG-2 glioma cells and retroviral vector producer cell lines was performed to provide a local source of interleukin-2 (IL-2) or IFN-gamma within the tumor and coinitiate an antitumor immune response. We demonstrated that local intratumoral production of IL-2 and IFN-gamma generates a cell-mediated antitumor response in vivo. This response was manifest as a diffuse infiltration of monocytes/macrophages, CD4+ and CD8+ T cells, and activation of microglial OX42+ cells in intracerebral RG2 tumors. The cell-mediated antitumor immune response resulted in the early suppression of intracranial and subcutaneous tumor growth, but the effect was not sustained and there were no tumor regressions. The absence of increased survival of animals with intracranial tumors is explained in part by the severe central nervous system toxicity caused by local production of IL-2 and IFN-gamma. Central nervous system toxicity induced blood-brain barrier disruption, vasogenic brain edema, and dislocation of the brain midline structures, as observed by dynamic magnetic resonance imaging and direct measurements of tissue water content. The clinical application of IL-2 and IFN-gamma gene transfer therapy for intracerebral tumors must consider the potential for severe vasogenic brain edema associated with intracerebral production of these cytokines.

Corticotropin-releasing factor decreases vasogenic brain edema.

We report the first series of studies comparing the anti-edematous effects of human corticotropin-releasing factor (hCRF) and dexamethasone in an experimental model of vasogenic peritumoral brain edema. Both hCRF and dexamethasone effectively decreased blood-brain barrier (BBB) permeability of intracerebral RG2 gliomas in rats as observed by contrast-enhanced T(1)-weighted magnetic resonance imaging. A decrease in the water content of tumor and peritumoral brain tissue was observed with proton-density magnetic resonance imaging and confirmed by direct wet/dry tissue measurements. The calculated ED(50) for hCRF was 59 micrograms/kg s.c. twice a day, and that for dexamethasone was 0.61 mg/kg i.m. twice a day; the hCRF:dexamethasone dose-potency ratio was 120:1 on a molar basis. The anti-edematous action of hCRF is not mediated by the release of adrenal corticosteroids. A direct action of hCRF on the tumor microvasculature results in restoration of BBB integrity and up-regulation of BBB-specific protein expression. The average survival time with chronic treatment was prolonged significantly in the hCRF-treated group (35 days) compared with the dexamethasone-treated group (28 days; P < 0.05) and the saline-treated control group (22 days; P < 0.0001). hCRF, as an alternative to corticosteroid therapy, may provide substantial benefits with respect to reducing the major side effects encountered with long-term, high-dose corticosteroid treatment.

Use of phosphorous-31 nuclear magnetic resonance spectroscopy to determine safe timing of chemotherapy after hepatic resection.

Liver resection induces accelerated growth of residual hepatic micrometastases. Adjuvant chemotherapy may improve outcome if administered early after resection but may prove lethal if initiated prior to completion of DNA synthesis in regenerating liver. This study investigates phosphorus-31 nuclear magnetic resonance ((31)P-NMR) as a noninvasive tool for measuring energy changes reflective of hepatic DNA synthesis and for predicting safe timing of chemotherapy after 70% hepatectomy. To evaluate metabolic changes in regenerating liver, quantitative three-dimensional (31)P-NMR was performed, using the technique of chemical shift imaging at various time points after 70% hepatectomy in adult male Fischer rats. Animals receiving a course of 2'-deoxy-5-fluorouridine (FUDR; 100 mg/kg, i.p. four times per day x 5), initiated at the time of operation, were also evaluated to observe the effects of chemotherapy on liver regeneration. Forty-eight hours after resection, hepatic nucleoside triphosphate (NTP), which reflects ATP content, fell 37% (P < 0.03) in animals undergoing hepatectomy alone. By contrast, animals receiving FUDR after hepatectomy demonstrated a mitigated NTP response, with a drop of only 17% (P = not significant), suggesting that interruption of DNA synthesis leads to a reduced consumption of ATP. Direct measures of DNA synthesis and nuclear proliferation were correlated with NMR findings. [(3)H]Thymidine incorporation and Ki67 immunohistochemistry were performed on liver samples from rats undergoing 70% hepatectomy with and without FUDR. Both [(3)H]thymidine incorporation and Ki67 expression were inhibited significantly at 48 h in animals receiving hepatectomy and FUDR, compared with those not treated with FUDR. To determine whether NMR changes could be used to identify safe timing of chemotherapy after hepatectomy, rats were treated with a 5-day course of FUDR initiated either prior to or after NMR changes normalized. Animals treated with FUDR at the point of NTP normalization (72 h) showed significantly improved survival over those that began treatment at operation (75 % versus 17 %; P = 0.0005, log rank test). FUDR inhibits hepatic DNA synthesis and influences mortality if administered too early after hepatectomy. Chemical shift imaging is a noninvasive tool that can identify metabolic changes coinciding with DNA synthesis and nuclear proliferation after hepatectomy. (31)P-NMR may be useful for determining safe timing of chemotherapy after liver resection.

CO2 laser photoacoustic measurements of ethanol absorption coefficients within infrared region of 9.2-10.8 µm.

Absorption coefficients of the ethanol vapors at atmospheric pressure and room temperature were measured by photoacoustic technique using a cw, line-tunable, frequency-stabilized CO2 laser as radiation source. The spectrum of the employed CO2 laser includes 54 lines with wavelengths in the infrared region of 9.2-10.8µm and power levels up to 4.7W. Measurements revealed a predominant absorption for ethanol within 9.4µm band of the CO2 laser spectrum, where the highest values of the absorption coefficients were recorded: 3.68cm(-1)atm(-1) at 9R(20) line and 3.65cm(-1)atm(-1) at 9R(22) line. The estimated detection range covers six orders of magnitude, from a minimum of 30ppbV to a maximum of 4% concentration of ethanol in nitrogen, which proves the suitability of the photoacoustic technique for accurate measurements of the ethanol concentration in various applications.

Mesostructured silica and aluminosilicate carriers for oxytetracycline delivery systems.

Oxytetracycline delivery systems containing various MCM-type silica and aluminosilicate with different antibiotic content were developed in order to establish the influence of the support structural and textural properties and aluminum content on the drug release profile. The antibiotic molecules were loaded into the support mesochannels by incipient wetness impregnation method using a drug concentrated aqueous solution. The carriers and drug-loaded materials were investigated by small- and wide-angle XRD, FTIR spectroscopy, TEM and N2 adsorption-desorption isotherms. Faster release kinetics of oxytetracycline from uncalcined silica and aluminosilicate supports was observed, whereas higher drug content led to lower delivery rate. The presence of aluminum into the silica network also slowed down the release rate. The antimicrobial assays performed on Staphylococcus aureus clinical isolates showed that the oxytetracycline-loaded materials containing MCM-41-type mesoporous silica or aluminosilicate carriers inhibited the bacterial development.

The in vivo effect of bryostatin-1 on paclitaxel-induced tumor growth, mitotic entry, and blood flow.

Pretreatment of tumor cells with the protein kinase C (PKC) inhibitor bryostatin-1 enhances the cytotoxicity of most chemotherapeutic agents. However, in the case of paclitaxel, this effect has been shown in vitro to be best achieved when bryostatin-1 follows (rather than precedes) paclitaxel treatment. With combination trials of bryostatin-1 and paclitaxel planned for clinical trials and with only in vitro data available regarding drug sequence, we elected to undertake an in vivo study evaluating the effect of sequential bryostatin-1 and paclitaxel in a tumor-bearing mouse model and to correlate this effect to cell cycle events, tumor metabolism, and tumor blood flow. At the maximum tolerated i.p. dose, bryostatin-1 at 80 microg/kg resulted in a small but significant increase in tumor doubling time (4.2 +/- 0.3 days) compared with control tumors (3.0 +/- 0.3 days; P < 0.01). Mice treated with i.v. paclitaxel, administered at a dose of 12 mg/kg every 12 h for three doses, weekly for 3 weeks, had a tumor doubling time of 23.4 +/- 1.7 days. Mice pretreated with i.p. bryostatin-1 (80 microg/kg) followed 12 h later by i.v. paclitaxel (12 mg/kg every 12h for three doses) weekly for 3 weeks had a tumor doubling time of 9.7 +/- 1.1 days. This was significantly less (P < .001) than paclitaxel alone, which indicated an inhibitory effect by bryostatin-1 on paclitaxel therapy. In comparison, tumor-bearing mice that were treated with the same dose but with the sequence of paclitaxel followed by bryostatin-1 had a tumor doubling time of 29.6 +/- 0.6 days. This was significantly greater than the tumor doubling times for any condition tested (P < 0.01), demonstrating the sequence dependence of this combination. The efficacy of paclitaxel is dependent on mitotic entry, a step that requires activation of p34cdc2 kinase activity. Treatment with paclitaxel in vivo increased p34 cdc2 kinase activity in the mouse mammary tumors, whereas administration of bryostatin-1 before paclitaxel prevented the p34cdc2 kinase activation by paclitaxel. This was further evaluated in vitro by flow cytometry in MKN-74 human gastric cancer cells. As determined by MPM-2 labeling, which identifies cells in mitosis, pretreatment with bryostatin-1 prevented paclitaxel-treated cells from entering mitosis. Bryostatin-1 has been reported to induce changes in muscle metabolism and to decrease muscle blood flow. These events could impact on the interaction of bryostatin-1 with paclitaxel. Using proton-decoupled phosphorus nuclear magnetic resonance (31P-NMR) spectroscopy in vivo, bryostatin-1 at 80 micro1g/kg induced a decrease in both intratumoral pH and high-energy phosphates. In vivo perfusion studies, using dynamic enhanced NMR imaging with gadolinium diethylenetriamine pentaacetic acid, also demonstrated decreased tumor blood flow. These studies suggest that the inhibition of tumor response to paclitaxel by bryostatin-1 is multifactorial and includes such diverse factors as inhibition of cell entry into mitosis, a decrease in pH and energy metabolism, and a decrease in tumor blood flow. These results indicate that, as this combination enters Phase I clinical trials, the sequence of paclitaxel followed by bryostatin-1 will be critical in the clinical trial design.