The relationship between regional variations in blood flow and histology in a transplanted rat fibrosarcoma

The regional distribution of blood flow to the LBDS1 fibrosarcoma, transplanted into the subcutaneous site in rats, was investigated using the readily diffusible compound 14C-iodo-antipyrine (14C-IAP). Quantitative autoradiography was used to establish absolute values of specific blood flow F for 100 X 100 X 20 microns adjacent tissue volumes of the unperturbed tumour. Mean blood flow to whole tumours was found to decrease with increase in tumour size. This relationship was abolished if blood flow was only measured in sections cut from the periphery of the tumours. Detailed analysis of a sub-group of tumours showed that blood flow to individual tumours was heterogeneous. The range of blood flow was large, indicating that mean blood flow to a whole tumour is a poor reflection of the blood perfusion pattern of that tumour. Necrotic tumour regions were usually very poorly perfused. With the exception of the smallest tumours studied, blood flow was lower in the centre of tumours than in the periphery. Necrosis also tended to develop centrally. However, the peripheral to central gradient of blood flow was apparent even when densely cellular, viable tumour regions and necrotic regions were analysed separately. The decrease in blood flow with tumour size was also apparent in densely cellular, viable tumour regions when analysed separately. Qualitative comparison of tumour histology and regional blood flow showed that there were areas of very low blood flow associated with viable tumour regions. Less common were areas of rather high blood flow associated with necrotic tumour regions. A complicated relationship exists between tumour histology and blood flow. The quantitative autoradiography technique is suitable for investigating the most poorly perfused and the most well perfused viable fractions of animal tumours which may limit the efficacy of different types of therapy

Synthesis of [3-C-13]-2,3-dihydroxy-4-methoxybenzaldehyde

An efficient synthesis of [3-13C]-2,3-dihydroxy-4-methoxybenzaldehyde, an isotopically labelled probe of a common intermediate used in the synthesis of a number of biologically relevant molecules, has been achieved in 9 steps from an acyclic, non-aromatic precursor. A 13C label for molecular imaging was introduced in a linear synthesis from the reaction of [13C]-labelled methyl iodide with glutaric monomethyl ester chloride. Cyclisation then aromatisation gave 1,3-dimethoxybenzene and an additional methoxy group was introduced by a formylation/Baeyer–Villiger/hydrolysis/methylation sequence. Subsequent ortho-formylation and selective demethylation yielded the desired [3-13C]-2,3-dihydroxy-4-methoxybenzaldehyde

Quantum transport of two-dimensional Dirac fermions in SrMnBi2

We report two-dimensional quantum transport in SrMnBi$_2$ single crystals. The linear energy dispersion leads to the unusual nonsaturated linear magnetoresistance since all Dirac fermions occupy the lowest Landau level in the quantum limit. The transverse magnetoresistance exhibits a crossover at a critical field $B^*$ from semiclassical weak-field $B^2$ dependence to the high-field linear-field dependence. With increase in the temperature, the critical field $B^*$ increases and the temperature dependence of $B^*$ satisfies quadratic behavior which is attributed to the Landau level splitting of the linear energy dispersion. The effective magnetoresistant mobility $\mu_{MR}\sim 3400$ cm$^2$/Vs is derived. Angular dependent magnetoresistance and quantum oscillations suggest dominant two-dimensional (2D) Fermi surfaces. Our results illustrate the dominant 2D Dirac fermion states in SrMnBi$_2$ and imply that bulk crystals with Bi square nets can be used to study low dimensional electronic transport commonly found in 2D materials like graphene.Comment: 5 papges, 4 figure

High resolution miniature dilatometer based on AFM piezocantilever

Thermal expansion, or dilation, is closely related to the specific heat, and provides useful information regarding material properties. The accurate measurement of dilation in confined spaces coupled with other limiting experimental environments such as low temperatures and rapidly changing high magnetic fields requires a new sensitive millimeter size dilatometer that has little or no temperature and field dependence. We have designed an ultra compact dilatometer using an atomic force microscope (AFM) piezoresistive cantilever as the sensing element and demonstrated its versatility by studying the charge density waves (CDWs) in alpha uranium to high magnetic fields (up to 31 T). The performance of this piezoresistive dilatometer was comparable to that of a titanium capacitive dilatometer.Comment: 9 pages, 3 figures, submitted to Review of Scientific Instrument

Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to VEGF-R tyrosine kinase inhibition

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In this work we studied the functional differences between the microcirculation of murine tumours that only express single isoforms of vascular endothelial growth factor-A (VEGF), VEGF120 and VEGF188, and the effect of VEGF receptor tyrosine kinase (VEGF-R TK) inhibition on their functional response to the vascular disrupting agent, combretastatin A-4 phosphate (CA-4-P). We used measurement of fluorescentlylabelled red blood cell (RBC) velocities in tumour microvessels to study this functional response. RBC velocity for control VEGF120-expressing tumours was over 50% slower than for control VEGF188-expressing tumours, which may be due to the immature and haemorrhagic vasculature of the VEGF120 tumour. After chronic treatment with a VEGF-R tyrosine kinase inhibitor, SU5416, RBC velocities in VEGF120 tumours were significantly increased compared to control VEGF120 tumours, and similar to velocities in both VEGF188 treatment groups. Control and SU5416 treated VEGF188 tumours were not different from each other. Treatment of VEGF120 tumours with SU5416 reduced their vascular response to CA-4-P to a similar level to the VEGF188 tumours. Differential expression of VEGF isoforms not only affected vascular function in untreated tumours but also impacted on response to a vascular disrupting drug, CA-4-P, alone and in combination with an anti-angiogenic approach involving VEGF-R TK inhibition. Analysis of RBC velocities is a useful tool in measuring functional responses to vascular targeted treatments.This study is funded by the Cancer Research UK

High-magnetic field lattice length changes in URu2Si2

We report high magnetic field (up to 45 T) c-axis thermal expansion and magnetostriction experiments on URu2Si2 single crystals. The sample length change associated with the transition to the hidden order phase becomes increasingly discontinous as the magnetic field is raised above 25 T. The re-entrant ordered phase III is clearly observed in both the thermal expansion and magnetostriction above 36 T, in good agreement with previous results. The sample length is also discontinuous at the boundaries of this phase, mainly at the upper boundary. A change in the sign of the coefficient of thermal-expansion is observed at the metamagnetic transition (B_M = 38 T) which is likely related to the existence of a quantum critical end point.Comment: 5 pages, 4 figures, to be published in PR

Magnetic field induced lattice anomaly inside the superconducting state of CeCoIn5_5: evidence of the proposed Fulde-Ferrell-Larkin-Ovchinnikov state

We report high magnetic field linear magnetostriction experiments on CeCoIn$_5$ single crystals. Two features are remarkable: (i) a sharp discontinuity in all the crystallographic axes associated with the upper superconducting critical field $B_{c2}$ that becomes less pronounced as the temperature increases; (ii) a distinctive second order-like feature observed only along the c-axis in the high field (10 T $\lesssim B \leq B_{c2}$) low temperature ($T \lesssim$ 0.35 K) region. This second order transition is observed only when the magnetic field lies within 20$^o$ of the ab-planes and there is no signature of it above $B_{c2}$, which raises questions regarding its interpretation as a field induced magnetically ordered phase. Good agreement with previous results suggests that this anomaly is related to the transition to the Fulde-Ferrel-Larkin-Ovchinnikov superconducting state.Comment: 3 figures, 5 page

Measuring Red Blood Cell Velocity with a Keyhole Tracking Algorithm

A tracking algorithm is proposed to measure the velocity of red blood cells traveling through microvessels of tumors growing in skin flaps implanted on mice. The tracking is based on a keyhole model that describes the probable movement of a segmented cell between contiguous frames in a video sequence. When a history of movements exists, past, present and a predicted landing position define two regions of probability with a keyhole shape. This keyhole is used to de- termine if cells in contiguous frames should be linked to form tracks. Pre-processing segments cells from background and post-processing joins tracks and discards links that could have been formed due to noise or uncertainty. The algorithm pre- sents several advantages over traditional methods such as kymographs or particle image velocimetry: manual interven- tion is restricted to the thresholding, several vessels can be analyzed simultaneously, algorithm is robust to noise and a wealth of statistical measures can be obtained. Two tumors with different geometries were analyzed; average velocities were 211±136 [μm/s] (mean±std) with a range 15.9-797 [μm/s], and 89±62 [μm/s] with a range 5.5-300 [μm/s] respec- tively, which are consistent with previous results in the litera- ture