Radioimmunotherapy Improves Survival of Rats with Microscopic Liver Metastases of Colorectal Origin

BACKGROUND: Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases. METHODS: Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 x 10(6) CC531 tumor cells. The biodistribution of (111)In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of (177)Lu-labeled MG1 was determined and the therapeutic efficacy of (177)Lu-MG1 at MTD was compared with that of (177)Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival. RESULTS: (111)In-MG1 preferentially accumulated in CC531 liver tumors (9.2 +/- 3.7%ID/g), whereas (111)In-UPC-10 did not (0.8 +/- 0.1%ID/g). The MTD of (177)Lu-MG1 was 400 MBq/kg body weight. Both the administration of (177)Lu-MG1 and (177)Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received (177)Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of (177)Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of (177)Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940). CONCLUSION: This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors

Evaluation of endogenous miRNA reference genes across different zebrafish strains, developmental stages and kidney disease models

The majority of kidney diseases arise from the loss of podocytes and from morphological changes of their highly complex foot process architecture, which inevitably leads to a reduced kidney filtration and total loss of kidney function. It could have been shown that microRNAs (miRs) play a pivotal role in the pathogenesis of podocyte-associated kidney diseases. Due to their fully functioning pronephric kidney, larval zebrafish have become a popular vertebrate model, to study kidney diseases in vivo. Unfortunately, there is no consensus about a proper normalization strategy of RT-qPCR-based miRNA expression data in zebrafish. In this study we analyzed 9 preselected candidates dre-miR-92a-3p, dre-miR-206-3p, dre-miR-99-1, dre-miR-92b-3p, dre-miR-363-3p, dre-let-7e, dre-miR-454a, dre-miR-30c-5p, dre-miR-126a-5p for their capability as endogenous reference genes in zebrafish experiments. Expression levels of potential candidates were measured in 3 different zebrafish strains, different developmental stages, and in different kidney disease models by RT-qPCR. Expression values were analyzed with NormFinder, BestKeeper, GeNorm, and DeltaCt and were tested for inter-group differences. All candidates show an abundant expression throughout all samples and relatively high stability. The most stable candidate without significant inter-group differences was dre-miR-92b-3p making it a suitable endogenous reference gene for RT-qPCR-based miR expression zebrafish studies

Bound States in Mildly Curved Layers

It has been shown recently that a nonrelativistic quantum particle constrained to a hard-wall layer of constant width built over a geodesically complete simply connected noncompact curved surface can have bound states provided the surface is not a plane. In this paper we study the weak-coupling asymptotics of these bound states, i.e. the situation when the surface is a mildly curved plane. Under suitable assumptions about regularity and decay of surface curvatures we derive the leading order in the ground-state eigenvalue expansion. The argument is based on Birman-Schwinger analysis of Schroedinger operators in a planar hard-wall layer.Comment: LaTeX 2e, 23 page

Vortex phases in mesoscopic cylinders with suppressed surface superconductivity

Vortex structures in mesoscopic cylinder placed in external magnetic field are studied under the general de Gennes boundary condition for the order parameter corresponding to the suppression of surface superconductivity. The Ginzburg-Landau equations are solved based on trial functions for the order parameter for vortex-free, single-vortex, multivortex, and giant vortex phases. The equilibrium vortex diagrams in the plane of external field and cylinder radius and magnetization curves are calculated at different values of de Gennes "extrapolation length" characterizing the boundary condition for the order parameter. The comparison of the obtained variational results with some available exact solutions shows good accuracy of our approach.Comment: RevTex, 11 pages, 10 figure

Meissner effect, Spin Meissner effect and charge expulsion in superconductors

The Meissner effect and the Spin Meissner effect are the spontaneous generation of charge and spin current respectively near the surface of a metal making a transition to the superconducting state. The Meissner effect is well known but, I argue, not explained by the conventional theory, the Spin Meissner effect has yet to be detected. I propose that both effects take place in all superconductors, the first one in the presence of an applied magnetostatic field, the second one even in the absence of applied external fields. Both effects can be understood under the assumption that electrons expand their orbits and thereby lower their quantum kinetic energy in the transition to superconductivity. Associated with this process, the metal expels negative charge from the interior to the surface and an electric field is generated in the interior. The resulting charge current can be understood as arising from the magnetic Lorentz force on radially outgoing electrons, and the resulting spin current can be understood as arising from a spin Hall effect originating in the Rashba-like coupling of the electron magnetic moment to the internal electric field. The associated electrodynamics is qualitatively different from London electrodynamics, yet can be described by a small modification of the conventional London equations. The stability of the superconducting state and its macroscopic phase coherence hinge on the fact that the orbital angular momentum of the carriers of the spin current is found to be exactly $\hbar/2$, indicating a topological origin. The simplicity and universality of our theory argue for its validity, and the occurrence of superconductivity in many classes of materials can be understood within our theory.Comment: Submitted to SLAFES XX Proceeding

Maximal Net Baryon Density in the Energy Region Covered by NICA

There are several theoretical indications that the energy region covered by the proposed NICA accelerator in Dubna is an extremely interesting one. We present a review of data obtained in relativistic heavy ion collisions and show that there is a gap around 10 GeV where more and better precise measurements are needed. The theoretical interpretation can only be clarified by covering this energy region. In particular the strangeness content needs to be determined, data covering the full phase space ($4 \pi$) would be very helpful to establish the thermal parameters of a possible phase transition.Comment: 8 pages 8 figure

Global forecasting of thermal health hazards: the skill of probabilistic predictions of the Universal Thermal Climate Index (UTCI)

Although over a hundred thermal indices can be used for assessing thermal health hazards, many ignore the human heat budget, physiology and clothing. The Universal Thermal Climate Index (UTCI) addresses these shortcomings by using an advanced thermo-physiological model. This paper assesses the potential of using the UTCI for forecasting thermal health hazards. Traditionally, such hazard forecasting has had two further limitations: it has been narrowly focused on a particular region or nation and has relied on the use of single ‘deterministic’ forecasts. Here, the UTCI is computed on a global scale,which is essential for international health-hazard warnings and disaster preparedness, and it is provided as a probabilistic forecast. It is shown that probabilistic UTCI forecasts are superior in skill to deterministic forecasts and that despite global variations, the UTCI forecast is skilful for lead times up to 10 days. The paper also demonstrates the utility of probabilistic UTCI forecasts on the example of the 2010 heat wave in Russia

Comet and cytogenetic tests as tools for evaluating genomic instability in seeds of Oryza sativa L. and Phaseolus vulgaris L. from gene banks

This study aimed to assess the feasibility of comet and cytogenetic tests as tools for evaluating genomic instability in seeds of Oryza sativa L. (rice) and Phaseolus vulgaris (beans) L. from gene banks. Rice and beans were exposed to methyl methanesulfonate (MMS) as a reference DNA damaging agent. Seeds of two accessions of rice and beans were obtained from Embrapa Rice and Beans - Brazil. Seed groups were imbibed in three concentrations of MMS for three periods of time to carry out cytogenetic tests, and for one period for the comet test. At concentrations of 10 and 15 mg/L, MMS induced cytotoxic and/or mutagenic effects in the meristematic cells of roots from all the accessions of both species. In the comet test, MMS induced genotoxic effects at all the concentrations in the evaluated accessions of rice and beans, except in one accession of beans at the lowest concentration (5 mg/L). Both species showed sensitivity to MMS. The comet test can be proposed for the measurement of genomic instability in accessions of rice and beans in gene banks, as being more sensitive than the cytogenetic tests used