The application of electrosprayed minocycline-loaded PLGA microparticles for the treatment of glioblastoma.

The survival of patients with glioblastoma multiforme (GBM), the most common and invasive form of malignant brain tumors, remains poor despite advances in current treatment methods including surgery, radiotherapy, and chemotherapy. Minocycline is a semi-synthetic tetracycline derivative that has been widely used as an antibiotic and more recently, it has been utilized as an antiangiogenic factor to inhibit tumorigenesis. The objective of this study was to investigate the utilization of electrospraying process to fabricate minocycline-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with high drug loading and loading efficiency and to evaluate their ability to induce cell toxicity in human glioblastoma (i.e., U87-MG) cells. The results from this study demonstrated that solvent mixture of dicholoromethane (DCM) and methanol is the optimal solvent combination for minocycline and larger amount of methanol (i.e., 70:30) resulted in a higher drug loading. All three solvent ratios of DCM:methanol tested produced microparticles that were both spherical and smooth, all in the micron size range. The electrosprayed microparticles were able to elicit a cytotoxic response in U87-MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work provides proof of concept to the hypothesis that electrosprayed minocycline-loaded PLGA microparticles can be a promising agent for the treatment of GBM and could have potential application for cancer therapies.

Fabrication of Multifunctional Drug Loaded Magnetic Phase Supported Calcium Phosphate Nanoparticle for Local Hyperthermia Combined Drug Delivery and Antibacterial Activity.

Magnetic calcium phosphate nanoparticles are biocompatible and have attracted much attention as biomaterials for bone tissue engineering and theranostic applications. In this study, we report the fabrication of a biocompatible magnetic nickel ferrite supported fluorapatite nanoparticle as a bone substitute material with hyperthermia potential using a facile wet precipitation approach. The composition and magnetic properties of the sample were analyzed using X-ray diffraction (XRD) and a vibrating sample magnetometer (VSM). The presence of both magnetic (NiFe2O4 and γ-Fe2O3) and fluorapatite phases was identified, and the sample exhibited ferromagnetic behavior with saturation magnetization and coercivity of 3.08 emu/g and 109 Oe, respectively. The fabricated sample achieved the hyperthermia temperature of ∼43 °C under tumor mimic conditions (neglecting Brownian relaxation) in 2.67 min, and the specific loss power (SLP) was estimated to be 898 W/g(Ni+Fe) which is sufficient to prompt irreversible cell apoptosis. Biocompatibility of the synthesized nanoparticle was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay with fibroblast NIH 3T3 and L929 cells. An in vitro drug release experiment was conducted at pH 5 (tumor mimic) and 7.4 (physiological), which revealed a release of 49.8% in the former and 11.6% in the latter pH for 11 days. The prepared sample showed antibacterial activity against S. aureus.

Ventricular function and tissue characterization by cardiac magnetic resonance imaging following hospitalization for multisystem inflammatory syndrome in children: a prospective study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe life-threatening manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that often presents with acute cardiac dysfunction and cardiogenic shock. While recovery from acute illness is excellent, the long-term myocardial impact is unknown. OBJECTIVE: To compare cardiac MRI findings in children 6-9 months after their hospitalization with MIS-C against MRI findings in healthy controls to assess for residual myocardial disease. MATERIALS AND METHODS: We prospectively performed cardiac MRI on 13 children 6-9 months following their hospitalization with MIS-C: eight of these children had a history of left ventricle ejection fraction (LVEF) < 50%, persistent symptoms, or electrocardiogram (ECG) abnormalities and underwent clinical MRI; five of these children without cardiac abnormalities during their hospitalization underwent research MRIs. We compared their native T1 and T2 mapping values with those of 20 normal controls. RESULTS: Cardiac MRI was performed at 13.6 years of age (interquartile range [IQR] 11.9-16.4 years) and 8.2 months (IQR 6.8-9.6 months) following hospitalization. Twelve children displayed normal ejection fraction: left ventricle (LV) 57.2%, IQR 56.1-58.4; right ventricle (RV) 53.1%, IQR 52.0-55.7. One had low-normal LVEF (52%). They had normal extracellular volume (ECV) and normal T2 and native T1 times compared to controls. There was no qualitative evidence of edema. One child had late gadolinium enhancement (LGE) with normal ejection fraction, no edema, and normal T1 and T2 times. When stratifying children who had MIS-C according to history of LVEF <55% on echocardiography, there was no difference in MRI values. CONCLUSION: Although many children with MIS-C present acutely with cardiac dysfunction, residual myocardial damage 6-9 months afterward appears minimal. Long-term implications warrant further study.

Ventricular Function and Tissue Characterization By Cardiac MRI in Children Following Hospitalization for Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Study.

Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe life-threatening manifestation of SARS-CoV-2 infection. Acute cardiac dysfunction and resultant cardiogenic shock are common in children with MIS-C. While most children recover rapidly from acute illness, the long-term impact on the myocardium and cardiac function is unknown. Methods In this prospective study, cardiac MRI (CMR) was performed on patients <21 years of age with a history of MIS-C, 6-9 months following hospitalization. Per institutional protocol, patients with any history of LVEF<50%, persistent cardiorespiratory symptoms, or ECG abnormalities underwent clinical CMR. Research CMRs were offered to all others >10 years old. Native T1 and T2 mapping values were compared with 20 children with normal CMR examinations. Results We performed CMRs on 13 subjects at a median age of 13.6 years (interquartile range [IQR] 11.9-16.0) and a median time from hospitalization of 8.2 months (IQR 6.8-9.6). Twelve subjects displayed normal ventricular function with a median left ventricle ejection fraction (LVEF) of 57.2% (IQR 56.1-58.4) and median right ventricular (RV) EF of 53.1% (IQR 52.0-55.7). One subject had low normal EF (52%). There was normal T2 and native T1 as compared to normal controls. There was qualitatively no evidence of edema by T2 weighted imaging. One subject had late gadolinium enhancement (LGE) at the inferior insertion point and mid-ventricular inferolateral region, with normal EF, no evidence of edema or perfusion defects, and normal T1 and T2 times. When stratifying by a history of abnormal LVEF (LVEF <55%) on echocardiography, there was no difference in or parametric mapping values, though LVEF and LVEDV approached significance (p=0.06 and 0.05, respectively). Conclusions Although many children with MIS-C present acutely with cardiac dysfunction, myocardial recovery is overall excellent with minimal to no evidence of residual cardiac dysfunction or myocardial involvement. LVEF by CMR at 6-9 months among children with history of echocardiographic LV dysfunction is slightly lower, though does not meet statistical significance and is still within normal range. The long-term functional implications of this finding and the cardiac implications of MIS-C more broadly are unclear and warrant further study.

Upconversion, MRI imaging and optical trapping studies of silver nanoparticle decorated multifunctional NaGdF4:Yb,Er nanocomposite.

The multifunctional upconversion nanoparticles (UCNPs) are fascinating tool for biological applications. In the present work, photon upconverting NaGdF4:Yb,Er and Ag nanoparticles decorated NaGdF4:Yb,Er (NaGdF4:Yb,Er@Ag) nanoparticles were prepared using a simple polyol process. Rietveld refinement was performed for detailed crystal structural and phase fraction analysis. The morphology of the NaGdF4:Yb,Er@Ag was examined using high-resolution transmission electron microscope, which reveals silver nanoparticles of 8 nm in size were decorated over spherical shaped NaGdF4:Yb,Er nanoparticles with a mean particle size of 90 nm. The chemical compositions were confirmed by EDAX and inductively coupled plasma-optical emission spectrometry analyses. The upconversion luminescence (UCL) of NaGdF4:Yb,Er at 980 nm excitation showed an intense red emission. After incorporating the silver nanoparticles, the UCL intensity decreased due to weak scattering and surface plasmon resonance effect. The VSM magnetic measurement indicates both the UCNPs possess paramagnetic behaviour. The NaGdF4:Yb,Er@Ag showed computed tomography imaging. Magnetic resonance imaging study exhibited better T1 weighted relaxivity in the NaGdF4:Yb,Er than the commercial Gd-DOTA. For the first time, the optical trapping was successfully demonstrated for the upconversion NaGdF4:Yb,Er nanoparticle at near-infrared 980 nm light using an optical tweezer setup. The optically trapped UCNP possessing paramagnetic property exhibited a good optical trapping stiffness. The UCL of trapped single UCNP is recorded to explore the effect of the silver nanoparticles. The multifunctional properties for the NaGdF4:Yb,Er@Ag nanoparticle are demonstrated.

Application of iron oxide nanoparticles to control the release of minocycline for the treatment of glioblastoma.

Background: The utilization of iron oxide nanoparticles (Fe3O4 NPs) to control minocycline release rates from poly(lactic-co-glycolic acid) scaffolds fabricated from an easy/economical technique is presented. Results & methodology: A larger change in temperature and amount of minocycline released was observed for scaffolds with higher amounts of Fe3O4 NPs, demonstrating that nanoparticle concentration can control heat generation and minocycline release. Temperatures near a polymer's glass transition temperature can result in the polymer's chain becoming more mobile and thus increasing drug diffusion out of the scaffold. Elevated temperature and minocycline released from the scaffold can work synergistically to enhance glioblastoma cell death. Conclusion: This study suggests that Fe3O4 NPs are promising materials for controlling minocycline release from polymeric scaffolds by magnetic hyperthermia for the treatment of glioblastoma.

Structural Evolution and Magnetic Properties of Gd2Hf2O7 Nanocrystals: Computational and Experimental Investigations.

Structural evolution in functional materials is a physicochemical phenomenon, which is important from a fundamental study point of view and for its applications in magnetism, catalysis, and nuclear waste immobilization. In this study, we used x-ray diffraction and Raman spectroscopy to examine the Gd2Hf2O7 (GHO) pyrochlore, and we showed that it underwent a thermally induced crystalline phase evolution. Superconducting quantum interference device measurements were carried out on both the weakly ordered pyrochlore and the fully ordered phases. These measurements suggest a weak magnetism for both pyrochlore phases. Spin density calculations showed that the Gd3+ ion has a major contribution to the fully ordered pyrochlore magnetic behavior and its cation antisite. The origin of the Gd magnetism is due to the concomitant shift of its spin-up 4f orbital states above the Fermi energy and its spin-down states below the Fermi energy. This picture is in contrast to the familiar Stoner model used in magnetism. The ordered pyrochlore GHO is antiferromagnetic, whereas its antisite is ferromagnetic. The localization of the Gd-4f orbitals is also indicative of weak magnetism. Chemical bonding was analyzed via overlap population calculations: These analyses indicate that Hf-Gd and Gd-O covalent interactions are destabilizing, and thus, the stabilities of these bonds are due to ionic interactions. Our combined experimental and computational analyses on the technologically important pyrochlore materials provide a basic understanding of their structure, bonding properties, and magnetic behaviors.

NaGdF4:Yb,Er-Ag nanowire hybrid nanocomposite for multifunctional upconversion emission, optical imaging, MRI and CT imaging applications.

The effect of novel silver nanowire encapsulated NaGdF4:Yb,Er hybrid nanocomposite on the upconversion emission and bioimaging properties has been investigated. The upconvension nanomaterials were synthesised by polyol method in the presence of ethylene glycol, PVP and ethylenediamine. The NaGdF4:Yb,Er-Ag hybrid was formed with upconverting NaGdF4:Yb,Er nanoparticles of size ~ 80 nm and silver nanowires of thickness ~ 30 nm. The surface plasmon induced by the silver ion in the NaGdF4:Yb,Er-Ag nanocomposite resulted an intense upconversion green emission at 520 nm and red emission at 660 nm by NIR diode laser excitation at 980 nm wavelength. The UV-Vis-NIR spectral absorption at 440 nm and 980 nm, the intense Raman vibrational modes and the strong upconversion emission results altogether confirm the localised surface plasmon resonance effect of silver ion in the hybrid nanocomposite. MRI study of both NaGdF4:Yb,Er nanoparticle and NaGdF4:Yb,Er-Ag nanocomposite revealed the T1 relaxivities of 22.13 and 10.39 mM-1 s-1, which are larger than the commercial Gd-DOTA contrast agent of 3.08 mM-1 s-1. CT imaging NaGdF4:Yb,Er-Ag and NaGdF4:Yb,Er respectively showed the values of 53.29 HU L/g and 39.51 HU L/g, which are higher than 25.78 HU L/g of the CT contrast agent Iobitridol. The NaGdF4:Yb,Er and NaGdF4:Yb,Er-Ag respectively demonstrated a negative zeta potential of 54 mV and 55 mV, that could be useful for biological application. The in vitro cytotoxicity of the NaGdF4:Yb,Er tested in HeLa and MCF-7 cancer cell line by MTT assay demonstrated a cell viability of 90 and 80 %, respectively. But, the cell viability of NaGdF4:Yb,Er-Ag slightly decreased to 80 and 78%. The confocal microscopy imaging showed that the UCNPs are effectively up-taken inside the nucleolus of the cancer cells, and it might be useful for NIR laser-assisted phototherapy for cancer treatment. Graphical abstract.

Magnetic Active Water Filter Membrane for Induced Heating to Remove Biofoulants.

Filter membrane processes are water purification methods that use a partially permeable membrane to separate contaminants from drinking water and wastewater. Although highly effective, they suffer from biofouling due to the aggregation of bacteria and contaminants from the filtrate, thus rendering the membrane unusable. Consequently, the membrane needs to be replaced on a regular basis, which interrupts filtration operation, reduces throughput, and increases production cost. To address this issue, we have developed a new method to remove biofoulants via induction heating on a modified membrane with magnetite (Fe3O4) magnetic nanoparticles (MNPs) coating. Under applied alternating magnetic field (AMF), the surface temperature of the MNPs coating reaches 180 °C with a heating rate of 1.03 °C/s, which disintegrates biofoulants generated by model bacteria (Bacillus subtilis) and by those present in environmental water samples collected from a local lake. The heating process is capable of cleaning biofoulants for several cycles without damaging the filtration function of the membrane. Furthermore, magnetic induction heating on the modified membrane allows uniform high-intensity heat generation on a large surface in only a few minutes using inexpensive MNPs, which can potentially be scaled up for industrial applications.

Infant Mortality in Moscow: the Perils of Progress in Russia's World City.

This paper examines changes in infant mortality (IM) in Moscow, Russia's largest and most affluent city. Along with some remarkable improvements in Moscow's health system over the period between 2000 and 2014, the overall IM rate for Moscow's residents decreased substantially between 2000 and 2014. There remains, however, substantial intra-city variation across Moscow's 125 neighborhoods. Our regression models suggest that in higher-income neighborhoods measured by percent of population with rental income as a primary source, the IM rate is significantly lower than in lower-income neighborhoods measured by percent of population with transfer income as primary source (housing and utility subsidies and payments to working and low-income mothers, single mothers and foster parents). We also find that the density of physicians in a neighborhood is negatively correlated with the IM rate, but the effect is small. The density of nurses and hospital beds has no effect. We conclude that overall progress on health outcomes and measures of access does not, in itself, solve the challenge of intra-urban inequalities.

Effects of solvent used for fabrication on drug loading and release kinetics of electrosprayed temozolomide-loaded PLGA microparticles for the treatment of glioblastoma.

Glioblastoma multiforme (GBM) is the most common and invasive form of malignant brain tumors and despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with GBM still remains poor. Temozolomide (TMZ) is the chemotherapy drug that is most commonly given orally after surgical resection of these tumors. In this study, the effects of solvents (i.e., dichloromethane and acetonitrile) used for the fabrication of electrosprayed TMZ-loaded poly(lactic-co-glycolic acid) (PLGA) on drug loading, loading efficiency, drug release kinetics, surface morphology, and particle size were investigated. The results from this study demonstrated that by using a larger volume of a solvent with higher polarity (i.e., acetonitrile) which allows for a higher amount of hydrophilic TMZ to dissolve into the polymer solution, higher drug loading could be achieved. However, the particles fabricated with high amount of acetonitrile, which has a lower vapor pressure, had large pores and a smaller diameter which led to an initial burst release and high cumulative release at the end of the study. An optimal combination of the two solvents is needed to result in particles with a good amount of loading and minimal initial burst release. The electrosprayed microparticles were able to illicit a cytotoxic response in U-87 MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work indicated that electrospraying is a promising method for the fabrication of TMZ-loaded PLGA microparticles for the treatment of GBM and solvent composition can be altered to control drug loading and release kinetics. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2317-2324, 2019.

Reactive Oxygen Species Generation in Human Cells by a Novel Magnetic Resonance Imaging Contrast Agent.

The novel positive-contrast magnetic resonance imaging (MRI) marker C4 consists of an aqueous solution of cobalt chloride (CoCl2) complexed with the chelator N-acetylcysteine (NAC). We evaluated whether the presence of C4 or its components would produce reactive oxygen species (ROS, including hydroxyl, peroxyl, or other reactive oxygen species) in cultured cells. Human cancer or normal cells were incubated with 1% (w/v) CoCl2·6H2O or 2% NAC or a combination of both (1% CoCl2·6H2O : 2% NAC in an aqueous solution, abbreviated as Co : NAC) in the presence or absence of H2O2. Intracellular ROS levels were measured and quantified by change in relative fluorescence units. Student's t-tests were used. In all cell lines exposed to 1000 µM H2O2, the Co : NAC led to ≥94.7% suppression of ROS at 5 minutes and completely suppressed ROS at 60 and 90 minutes; NAC suppressed ROS by ≥76.6% at 5 minutes and by ≥94.5% at 90 minutes; and CoCl2·6H2O suppressed ROS by ≥37.2% at 30 minutes and by ≥48.6% at 90 minutes. These results demonstrate that neither Co : NAC nor its components generated ROS; rather, they suppressed ROS production in cultured cells, suggesting that C4 would not enhance ROS production in clinical use.

Toxicity Evaluation of a Novel Magnetic Resonance Imaging Marker, CoCl2-N-Acetylcysteine, in Rats.

C4 (cobalt dichloride-N-acetylcysteine [1% CoCl2:2% NAC]) is a novel magnetic resonance imaging contrast marker that facilitates visualization of implanted radioactive seeds in cancer brachytherapy. We evaluated the toxicity of C4. Rats were assigned to control (0% CoCl2:NAC), low-dose (0.1% CoCl2:2% NAC), reference-dose (C4), and high-dose (10% CoCl2:2% NAC) groups. Agent was injected into the left quadriceps femoris muscle of the rats. Endpoints were organ and body weights, hematology, and serum chemistry and histopathologic changes of tissues at 48 hours and 28 and 63 days after dosing. Student's t tests were used. No abnormalities in clinical signs, terminal body and organ weights, or hematologic and serum chemistry were noted, and no gross or histopathologic lesions of systemic tissue toxicity were found in any treatment group at any time point studied. At the site of injection, concentration-dependent acute responses were observed in all treatment groups at 48 hours after dosing and were recovered by 28 days. No myofiber degeneration or necrosis was observed at 28 or 63 days in any group. In conclusion, a single intramuscular dose of C4 produced no acute or chronic systemic toxicity or inflammation in rats, suggesting that C4 may be toxicologically safe for clinical use in cancer brachytherapy.

Magnetic Sensing Potential of Fe3O4 Nanocubes Exceeds That of Fe3O4 Nanospheres.

This paper highlights the relation between the shape of iron oxide (Fe3O4) particles and their magnetic sensing ability. We synthesized Fe3O4 nanocubes and nanospheres having tunable sizes via solvothermal and thermal decomposition synthesis reactions, respectively, to obtain samples in which the volumes and body diagonals/diameters were equivalent. Vibrating sample magnetometry (VSM) data showed that the saturation magnetization (Ms) and coercivity of 100-225 nm cubic magnetic nanoparticles (MNPs) were, respectively, 1.4-3.0 and 1.1-8.4 times those of spherical MNPs on a same-volume and same-body diagonal/diameter basis. The Curie temperature for the cubic Fe3O4 MNPs for each size was also higher than that of the corresponding spherical MNPs; furthermore, the cubic Fe3O4 MNPs were more crystalline than the corresponding spherical MNPs. For applications relying on both higher contact area and enhanced magnetic properties, higher-Ms Fe3O4 nanocubes offer distinct advantages over Fe3O4 nanospheres of the same-volume or same-body diagonal/diameter. We evaluated the sensing potential of our synthesized MNPs using giant magnetoresistive (GMR) sensing and force-induced remnant magnetization spectroscopy (FIRMS). Preliminary data obtained by GMR sensing confirmed that the nanocubes exhibited a distinct sensitivity advantage over the nanospheres. Similarly, FIRMS data showed that when subjected to the same force at the same initial concentration, a greater number of nanocubes remained bound to the sensor surface because of higher surface contact area. Because greater binding and higher Ms translate to stronger signal and better analytical sensitivity, nanocubes are an attractive alternative to nanospheres in sensing applications.

Depth-Resolved Multispectral Sub-Surface Imaging Using Multifunctional Upconversion Phosphors with Paramagnetic Properties.

Molecular imaging is very promising technique used for surgical guidance, which requires advancements related to properties of imaging agents and subsequent data retrieval methods from measured multispectral images. In this article, an upconversion material is introduced for subsurface near-infrared imaging and for the depth recovery of the material embedded below the biological tissue. The results confirm significant correlation between the analytical depth estimate of the material under the tissue and the measured ratio of emitted light from the material at two different wavelengths. Experiments with biological tissue samples demonstrate depth resolved imaging using the rare earth doped multifunctional phosphors. In vitro tests reveal no significant toxicity, whereas the magnetic measurements of the phosphors show that the particles are suitable as magnetic resonance imaging agents. The confocal imaging of fibroblast cells with these phosphors reveals their potential for in vivo imaging. The depth-resolved imaging technique with such phosphors has broad implications for real-time intraoperative surgical guidance.

Enzymatic synthesis of magnetic nanoparticles.

We report the first in vitro enzymatic synthesis of paramagnetic and antiferromagnetic nanoparticles toward magnetic ELISA reporting. With our procedure, alkaline phosphatase catalyzes the dephosphorylation of l-ascorbic-2-phosphate, which then serves as a reducing agent for salts of iron, gadolinium, and holmium, forming magnetic precipitates of Fe45±14Gd5±2O50±15 and Fe42±4Ho6±4O52±5. The nanoparticles were found to be paramagnetic at 300 K and antiferromagnetic under 25 K. Although weakly magnetic at 300 K, the room-temperature magnetization of the nanoparticles found here is considerably greater than that of analogous chemically-synthesized LnxFeyOz (Ln = Gd, Ho) samples reported previously. At 5 K, the nanoparticles showed a significantly higher saturation magnetization of 45 and 30 emu/g for Fe45±14Gd5±2O50±15 and Fe42±4Ho6±4O52±5, respectively. Our approach of enzymatically synthesizing magnetic labels reduces the cost and avoids diffusional mass-transfer limitations associated with pre-synthesized magnetic reporter particles, while retaining the advantages of magnetic sensing.

Patterning of magnetic thin films and multilayers using nanostructured tantalum gettering templates.

This work demonstrates that a nonmagnetic thin film of cobalt oxide (CoO) sandwiched between Ta seed and capping layers can be effectively reduced to a magnetic cobalt thin film by annealing at 200 °C, whereas CoO does not exhibit ferromagnetic properties at room temperature and is stable at up to ∼400 °C. The CoO reduction is attributed to the thermodynamically driven gettering of oxygen by tantalum, similar to the exothermic reduction-oxidation reaction observed in thermite systems. Similarly, annealing at 200 °C of a nonmagnetic [CoO/Pd]N multilayer thin film sandwiched between Ta seed and Ta capping layers results in the conversion into a magnetic [Co/Pd]N multilayer, a material with perpendicular magnetic anisotropy that is of interest for magnetic data storage applications. A nanopatterning approach is introduced where [CoO/Pd]N multilayers is locally reduced into [Co/Pd]N multilayers to achieve perpendicular magnetic anisotropy nanostructured array. This technique can potentially be adapted to nanoscale patterning of other systems for which thermodynamically favorable combination of oxide and gettering layers can be identified.

Low-cost carbon-silicon nanocomposite anodes for lithium ion batteries.

The specific energy of the existing lithium ion battery cells is limited because intercalation electrodes made of activated carbon (AC) materials have limited lithium ion storage capacities. Carbon nanotubes, graphene, and carbon nanofibers are the most sought alternatives to replace AC materials but their synthesis cost makes them highly prohibitive. Silicon has recently emerged as a strong candidate to replace existing graphite anodes due to its inherently large specific capacity and low working potential. However, pure silicon electrodes have shown poor mechanical integrity due to the dramatic expansion of the material during battery operation. This results in high irreversible capacity and short cycle life. We report on the synthesis and use of carbon and hybrid carbon-silicon nanostructures made by a simplified thermo-mechanical milling process to produce low-cost high-energy lithium ion battery anodes. Our work is based on an abundant, cost-effective, and easy-to-launch source of carbon soot having amorphous nature in combination with scrap silicon with crystalline nature. The carbon soot is transformed in situ into graphene and graphitic carbon during mechanical milling leading to superior elastic properties. Micro-Raman mapping shows a well-dispersed microstructure for both carbon and silicon. The fabricated composites are used for battery anodes, and the results are compared with commercial anodes from MTI Corporation. The anodes are integrated in batteries and tested; the results are compared to those seen in commercial batteries. For quick laboratory assessment, all electrochemical cells were fabricated under available environment conditions and they were tested at room temperature. Initial electrochemical analysis results on specific capacity, efficiency, and cyclability in comparison to currently available AC counterpart are promising to advance cost-effective commercial lithium ion battery technology. The electrochemical performance observed for carbon soot material is very interesting given the fact that its production cost is away cheaper than activated carbon. The cost of activated carbon is about $15/kg whereas the cost to manufacture carbon soot as a by-product from large-scale milling of abundant graphite is about $1/kg. Additionally, here, we propose a method that is environmentally friendly with strong potential for industrialization.

MRI characterization of cobalt dichloride-N-acetyl cysteine (C4) contrast agent marker for prostate brachytherapy.

Brachytherapy, a radiotherapy technique for treating prostate cancer, involves the implantation of numerous radioactive seeds into the prostate. While the implanted seeds can be easily identified on a computed tomography image, distinguishing the prostate and surrounding soft tissues is not as straightforward. Magnetic resonance imaging (MRI) offers superior anatomical delineation, but the seeds appear as dark voids and are difficult to identify, thus creating a conundrum. Cobalt dichloride-N-acetyl-cysteine (C4) has previously been shown to be promising as an encapsulated contrast agent marker. We performed spin-lattice relaxation time (T1) and spin-spin relaxation time (T2) measurements of C4 solutions with varying cobalt dichloride concentrations to determine the corresponding relaxivities, r1 and r2. These relaxation parameters were investigated at different field strengths, temperatures and orientations. T1 measurements obtained at 1.5 and 3.0 T, as well as at room and body temperature, showed that r1 is field-independent and temperature-independent. Conversely, the T2 values at 3.0 T were shorter than at 1.5 T, while the T2 values at body temperature were slightly higher than at room temperature. By examining the relaxivities with the C4 vials aligned in three different planes, we found no orientation-dependence. With these relaxation characteristics, we aim to develop pulse sequences that will enhance the C4 signal against prostatic stroma. Ultimately, the use of C4 as a positive contrast agent marker will encourage the use of MRI to obtain an accurate representation of the radiation dose delivered to the prostate and surrounding normal anatomical structures.

Tuning of alternative splicing--switch from proto-oncogene to tumor suppressor.

STAT5B, a specific member of the STAT family, is intimately associated with prostate tumor progression. While the full form of STAT5B is thought to promote tumor progression, a naturally occurring truncated isoform acts as a tumor suppressor. We previously demonstrated that truncated STAT5 is generated by insertion of an alternatively spliced exon and results in the introduction of an early termination codon. Present approaches targeting STAT proteins based on inhibition of functional domains of STAT's, such as DNA-binding, cooperative binding (protein-protein interaction), dimerization and phosphorylation will halt the action of the entire gene, both the proto-oncogenic and tumor suppressor functions of Stat5B. In this report we develop a new approach aimed at inhibiting the expression of full-length STAT5B (a proto-oncogene) while simultaneously enhancing the expression of STAT5∆B (a tumor suppressor). We have demonstrated the feasibility of using steric-blocking splice-switching oligonucleotides (SSOs) with a complimentary sequence to the targeted exon-intron boundary to enhance alternative intron/exon retention (up to 10%). The functional effect of the intron/exon proportional tuning was validated by cell proliferation and clonogenic assays. The new scheme applies specific steric-blocking splice-switching oligonucleotides and opens an opportunity for anti-tumor treatment as well as for the alteration of functional abilities of other STAT proteins.