Potential of magnetic resonance spectroscopy to detect metastasis in axillary lymph nodes in breast cancer

Focused pathological evaluation of axillary lymph nodes in breast cancer is gaining importance. Nuclear magnetic resonance (NMR) spectroscopy that assesses the whole of the specimen has the potential in evaluating micrometastases. The biochemical changes associated with breast cancer metastases in axillary nodes by in vitro NMR and its use in the detection of axillary metastases in a clinical setting in comparison with conventional histopathology is presented in this study. Eighty-eight lymph nodes obtained from 30 patients with breast cancer were investigated. Histopathology revealed metastases in 20 nodes from 11 patients, while in vitro NMR spectroscopy revealed metastases in 22 nodes. Out of these 22 nodes, 16 were the same, which showed metastases on histopathology, while 6 nodes have shown metastases only on in vitro magnetic resonance spectroscopy (MRS). These 6 nodes with suspicion of metastases on MRS were subjected to reevaluation with serial sectioning and immunohistochemistry, but no additional metastases were revealed. Forty metabolites could be identified from the MR spectrum of lymph nodes. The levels of the glycerophosphocholine-phosphocholine (GPC-PC), choline, lactate, alanine and uridine diphosphoglucose were elevated significantly in nodes with metastases. In addition, the intensity ratio of GPC-PC/threonine (Thr) was higher in nodes with metastases, and using this as marker, MRS detected the axillary metastases with a sensitivity, specificity and accuracy of 80%, 91% and 88%, respectively. Neoadjuvant chemotherapy (NACT) lowered the concentrations of GPC-PC and GPC-PC/Thr ratio. The accuracy of MRS in detecting metastases was 75% in patients who received NACT (n=9) as compared to 96% in those who did not (n=21). Our results demonstrate the potential of in vitro MRS in characterizing the metabolite profile of the axillary nodes with breast cancer metastases. It detected axillary metastases with reasonable accuracy and can be complementary to histopathological evaluation and immunohistochemistry.     

Biochemical characterization of metastatic lymph nodes of breast cancer patients by in vitro 1H magnetic resonance spectroscopy: a pilot study

Using one-dimensional (1D) and two-dimensional (2D) proton nuclear magnetic resonance (NMR) methods, the perchloric acid extract of involved (n = 11) and noninvolved (n = 12) axillary lymph nodes (ALN) of breast cancer patients was investigated. Resonances from 40 metabolites such as lactate (Lac), glucose, several amino acids (alanine, lysine, glutamic acid, glutamine, etc.), nucleotides (adenosine triphosphate, guanosine triphosphate, uridine triphosphate, uridine monophosphate, etc.), membrane metabolites [glycerophosphocholine (GPC), phosphocoline (PC), phosphoethanolamine (PE), choline] were unambiguously assigned in both the involved and noninvolved ALN. The concentration of PC/GPC (p = 0.002) was significantly higher in the involved compared to noninvolved nodes. In addition, the concentration of glycolytic product Lac (p = 0.0001) was also found to be significantly higher in involved nodes. Increased concentration of membrane metabolites PC/GPC may be attributed to increased membrane synthesis in malignant cells and, therefore, suggests the presence of metastatic cells in lymph nodes. The higher concentration of Lac is indicative of the presence of malignant cells that derive energy via anaerobic glycolytic pathway. Present results demonstrate the potentials of in vitro proton NMR in detecting malignant cells in ALN and such studies may have an important bearing in determining the prognosis of breast cancer patients.     

Skeletal muscle metabolism in Duchenne muscular dystrophy (DMD): an in-vitro proton NMR spectroscopy study

The metabolic differences in the skeletal muscle of patients with Duchenne muscular dystrophy (DMD) and normal subjects (controls) were investigated using in-vitro high-resolution proton NMR spectroscopy. In all, 56 metabolites were unambiguously identified in the perchloric acid extract of muscle tissue using one- and two-dimensional NMR. The concentrations of glycolytic substrate glucose (Glc; p < 0.05), gluconeogenic amino acids such as glutamine (Gln; p < 0.05) and alanine (Ala; p < 0.05) and the glycolytic product lactate (Lac; p < 0.05) were statistically significantly lower in DMD patients as compared to controls. A significant reduction in the concentrations of total creatine (TCr; p < 0.05), glycerophosphoryl choline + phosphoryl choline + carnitine (GPC/PC/Car; p < 0.05), choline (Cho; p < 0.05) and acetate (Ace; p < 0.05) was also observed in these patients. Decrease in the level of glucose may be attributed to the reduction in the concentrations of gluconeogenic substrates or membrane abnormalities in degenerated muscle of DMD patients. Lower levels of choline containing compounds indicate membrane abnormalities. Decrease in the concentration of lactate in the muscle of DMD patients may be due to the reduction in anaerobic glycolytic activity or lower substrate concentration. The decrease in the concentration of acetate may reflect reduced transport of fatty acids into mitochondria due to decreased concentration of carnitine in DMD patients. Kreb's cycle intermediate alpha-ketoglutarate was observed only in the diseased muscle, which is suggestive of predominant oxidative metabolism for energy generation.     

A conceptual high flux reactor design with scope for use in ADS applications

A 100 MWt reactor design has been conceived to support flux level of the order of 10¹⁵ n/cm²/s in selected flux trap zones. The physics design considers high enriched metallic alloy fuel in the form of annular plates placed in a D₂O moderator tank in a hexagonal lattice arrangement. By choosing a tight lattice pitch in the central region and double the lattice pitch in the outer region, it is possible to have both high fast flux and thermal flux trap zones. By design the flux level in the seed fuel has been kept lower than in the high flux trap zones so that the burning rate of the seed is reduced. Another important objective of the design is to maximize the time interval of refueling. As against a typical refueling interval of a few weeks in such high flux reactor cores, it is desired to maximize this period to as much as six months or even one year. This is possible to achieve by eliminating the conventional control absorbers and replacing them with a suitable amount of fertile material loading in the reactor. Requisite number of seedless thorium-aluminum alloy plates are placed at regular lattice locations vacated by seed fuel in alternate fuel layers. It is seen that these thorium plates are capable of acquiring asymptotic fissile content of 14 g/kg in about 100 days of irradiation at a flux level of 8 × 10¹⁴ n/cm²/s. In summary, the core has a relatively higher fast flux in the central region and high thermal flux in the outer region. The present physics design envisages a flat core excess reactivity for the longest possible cycle length of 6 months to one year. It is also possible to modify the design for constant subcriticality for about the same period or longer duration by considering neutron spallation source at the centre and curtailing the power density in the inner core region by shielding it with a layer of thoria fuel loading.      

Binder MIMO Channels

This paper introduces a multiple-input multiple-output channel model for the characterization of a binder of telephone lines. This model is based on multiconductor transmission line theory, and uses parameters that can be obtained from electromagnetic theory or measured data. The model generates frequency-dependent channel/binder transfer function matrices as a function of cable type, geometric line-spacing and twist-length parameters, and source--load configurations. The model allows the extraction of the magnitude and the phase of individual near end crosstalk, far end crosstalk, split-pair, and phantom transfer functions from the transfer function matrix of the binder. These individual crosstalk transfer functions are often found to be very sensitive to small imperfections in the binder. Examples of category 3 twisted pair American telephone lines and ldquoquadrdquo telephone cables are also presented.     

Reliability of microwave SiGe/Si heterojunction bipolar transistors

The degradation behavior of NPN Si/SiGe/Si heterojunction bipolar transistors, grown by solid-source molecular beam epitaxy (MBE), has been studied by accelerated lifetime testing at different ambient temperatures. The degradations of the dc current gain and the microwave performance of the devices are explained in terms of recombination enhanced impurity diffusion (REID) of boron atoms from the base region and the subsequent formation of parasitic energy barriers at the base-emitter and base-collector junctions     

Nanofluids: A New Class of Materials Produced from Nanoparticle Assemblies

We present evidence of a novel nanostructured fluid, a nanofluid, composed of molecular clusters of a polar organic dye and surfactant. These are not nanoparticles dispersed in a solvent; there are no solvent molecules present. These materials, which are solids under ambient conditions, are non‐reactively precipitated from a compressed CO₂ solution, resulting in a liquid‐like material, which we call a nanofluid. The precipitated dye–surfactant clusters are 1–4 nm in size. This nanofluid exhibits intense luminescent signatures, which are significantly blue‐shifted with respect to the dye powder or a solution of it. The X‐ray diffraction pattern did not show any structure in the low‐angle regime. The fluorinated surfactant is highly soluble in compressed CO₂. The polar dye does not dissolve in compressed CO₂ but is solubilized by electrostatic interactions with the surfactant head groups. We believe that the ultrafast and controlled precipitation from compressed CO₂ preserves the electrostatic coupling and promotes a structured molecular cluster. Additionally, we demonstrate the formation of organic nanoparticles using this controlled precipitation process from compressed CO₂.     

A 47 GHz Cross-Coupled VCO Employing High- Island-Gate Varactor for Phase Noise Reduction

A 47 GHz $LC$ cross-coupled voltage controlled oscillator (VCO) employing the high-$Q$ island-gate varactor (IGV) based on a 0.13 $mu{rm m}$ RFCMOS technology is reported in this work. To verify the improvement in the phase noise, two otherwise identical VCOs, each with an IGV and a conventional multi-finger varactor, were fabricated and the phase noise performance was compared. With $V_{DD}$ of 1.2 V and core power consumption of 3.86 mW, the VCOs with the IGV and the multi-finger varactor have a phase noise of $-$95.4 dBc/Hz and $-$91.4 dBc/Hz respectively, at 1 MHz offset, verifying the phase noise reduction with the introduction of the high-$Q$ IGV. The VCO with IGV exhibited an output power of around $-$15 dBm, leading to a FoM of $-$182.9 dBc/Hz and a tuning range of 3.35% (45.69 to 47.22 GHz).      

Balanced RF Duplexer with Low Interference Using Hybrid BAW Resonators for LTE Application

A balanced RF duplexer with low interference in an extremely narrow bandgap is proposed. The Long‐Term Evolution band‐7 duplexer should be designed to prevent the co‐existence problem with the WiFi band, whose fractional bandgap corresponds to only 0.7%. By implementing a hybrid bulk acoustic wave (BAW) structure, the temperature coefficient of frequency (TCF) value of the duplexer is successfully reduced and the suppressed interference for the narrow bandgap is performed. To achieve an RF duplexer with balanced Rx output topology, we also propose a novel balanced BAW Rx topology and RF circuit block. The novel balanced Rx filter is designed with both lattice‐ and ladder‐type configurations to ensure excellent attenuation. The RF circuit block, which is located between the antenna and the Rx filter, is developed to simultaneously function as a balance‐to‐unbalance transformer and a phase shift network. The size of the fabricated duplexer is as small as 2.0 mm × 1.6 mm. The maximum insertion loss of the duplexer is as low as 2.4 dB in the Tx band, and the minimum attenuation in the WiFi band is as high as 36.8 dB. The TCF value is considerably lowered to ?16.9 ppm/°C.     

Single‐Cell Investigations of Silver Nanoparticle–Bacteria Interactions

Interaction of bacteria with citrate‐reduced silver nanoparticles (AgNPs) of size 25 nm ± 8.5 nm is studied using Raman spectroscopy in conjunction with plasmon resonance imaging of single bacterial cells. Distribution of isolated nanoparticles (NPs) inside Escherichia coli (ATCC 25922; E. coli) is observed by hyperspectral imaging (HSI) as a function of incubation time. Time‐dependent degradation of bacterial DNA upon incubation of AgNPs with E. coli is proven by Raman spectroscopic studies. While attachment of NPs is evident in HSI, molecular changes are evident from the surface‐enhanced Raman spectra of adsorbed DNA and its fragments. Distinct enhancement of DNA features is observed upon interaction of AgNPs and the number of such distinct features increases with incubation time, reaches a maximum, and decreases afterwards. This systematic interaction of DNA with the NPs system and its gradual chemical evolution is proven by investigating isolated plasmid DNA. A comparative Raman study with silver ions has shown that DNA features are observable only when bacteria are incubated with AgNPs. Energetics of interaction examined with microcalorimetry suggests the exothermicity of ?1.547 × 10¹⁰ cal mol^?1 for the NP–bacteria system. Specific interaction of AgNPs with exocyclic nitrogen present in the bases, adenine, guanine, and cytosine, leads to the changes in DNA.