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Replication-competent viruses are being tested as tumor therapy agents. The fundamental premise of this therapy is the selective infection of the tumor cell population with the amplification of the virus. Spread of the virus in the tumor ultimately should lead to eradication of the cancer. Tumor virotherapy is unlike any other form of cancer therapy as the outcome depends on the dynamics that emerge from the interaction between the virus and tumor cell populations both of which change in time. We explore these interactions using a model that captures the salient biological features of this system in combination with in vivo data. Our results show that various therapeutic outcomes are possible ranging from tumor eradication to oscillatory behavior. Data from in vivo studies support these conclusions and validate our modeling approach. Such realistic models can be used to understand experimental observations, explore alternative therapeutic scenarios and develop techniques to optimize therapy. [ABSTRACT FROM AUTHOR]

Hurler Syndrome is corrected by allogeneic BMT by the action of donor enzyme on recipient tissue. In this paper, we describe monitoring of 39 patients transplanted in two centres to determine donor chimerism, enzyme level and residual substrate – expressed as dermatan sulphate to chondroitin sulphate ratio. We show that in fully engrafted recipients, the enzyme level, expressed as μmol/g total protein/h, post-transplant is 24.2 from an unrelated donor and 10.2 from a heterozygote family donor (P<0.0001). There is a tight relationship between mean post-transplant enzyme level and residual substrate – Spearman's rank correlation coefficient (Rho) was −0.76 and −0.80 at 12 and 24 months, respectively (P<0.0001). We propose that these differences affect patient outcome. As unrelated donor transplant outcomes improve and especially given the higher levels of donor cell engraftment following cord transplants, our data might influence donor selection where only heterozygote-matched family members are available.Bone Marrow Transplantation (2007) 39, 207–210. doi:10.1038/sj.bmt.1705569; published online 15 January 2007 [ABSTRACT FROM AUTHOR]

Echoplanar fMRI was used to measure changes in cortical activation during the performance of a simple hand movement task under three types of voluntary control. Each of three imaging series alternated a task with rest: passive (in which the experimenter moved the hand), voluntary against low resistance, and voluntary against higher resistance. Contralateral activation was observed in the supplementary motor area (SMA), the primary motor cortex (M1), and the somatosensory cortex (S1) in all three tasks in each subject, whereas ipsilateral activation differed in each cortical region for each task. SMA had the widest prevalence of ipsilateral activation in all three tasks. In the M1, ipsilateral activation was observed in all but 1 subject in the two voluntary tasks but in only a few subjects in the S1 in any of the tasks. Quantitative changes in signal intensity and spatial extent of activation differentiated the voluntary tasks from the passive task and were most pronounced in the S1. [ABSTRACT FROM AUTHOR]

Last year marked the 20th anniversary of the Foreign Corrupt Practices Act (FCPA) of 1977. The FCPA is the first and only statute prohibiting bribery and other corrupt business practices by U.S. citizens and companies conducting business overseas. This paper provides an overview of the FCPA during the two decades of its existence. More specifically, the objectives of this paper are four-fold. First, the paper provides background information about the FCPA of 1977 and subsequent amendments in 1988. Second, the paper discusses the enforcement of the FCPA since its passage by examining the number of cases prosecuted under the FCPA and the respective penalties imposed. Third, the paper discusses the economic impact of the FCPA by addressing whether the FCPA places U.S. firms at a competitive disadvantage. Fourth, the paper provides public policy recommendations to expand the reach and scope of the FCPA. It covers efforts to criminalize bribery through multilateral organizations, such as the Organization for Economic Cooperation and Development (OECD), the World Trade Organization (WTO), and the Organization of American States (OAS). It also covers bilateral arrangements and efforts by nongovernmental organizations such as Transparency International. [ABSTRACT FROM AUTHOR]

The Arabidopsis Gα subunit, GPα1, was expressedwithin Escherichia coli by co-transformation with the expressionvector and the dnaY gene which encodes tRNAArg AGA/AGG. Isolation of the recombinant GPα1 in a highly pureform could be achieved by a combination of anion exchange and dyeaffinity chromatography or by a single step affinity procedure viachromatography on 4-amino-anilido-GTP agarose. The recombinant proteinyielded by both procedures was highly active and bound GTPγS withan apparent Kd in the nM range. GTPγS binding wasstimulated two-fold in the presence of Zn2+ compared with that inthe presence of Mg2+, Mn2+ or Ca2+.Abbreviations: 4aaGTP, 4-amino-anilido-GTP; GTPγS,guanosine- 5′-(3-O-thiotriphosphate), PMSF,phenylmethylsulphonyl fluoride; PVDF, polvinylidene fluoride;rGPα1, recombinant GPα1 [ABSTRACT FROM AUTHOR]

Decametric radio observations of Jupiter were made before, during, and after the impacts of the fragments of the comet S-L 9 with the planet, from the University of Florida Radio Observatory, the Maipu Radio Astronomy Observatory of the University of Chile, and the Owens Valley Radio Observatory of the California Institute of Technology. The decametric radiation was monitored at frequencies from 16.7 to 32 MHz. The minimum detectable flux densities were on the order of 30 kJy, except for that of the large 26.3 MHz array in Florida, which was about 1 kJy. There was no significant enhancement or suppression of the decametric L-burst or S-burst emission with respect to normal activity patterns that might be attributed to the fragment entries. However, a burst of left-hand elliptically polarized radiation having a considerably longer duration than an L-burst was observed almost simultaneously with the impact of the large fragment Q2, and another with right-hand elliptical polarization was observed simultaneously with Q1. We consider the possibility that these two bursts were emitted just above the local electron cyclotron frequencies from the southern and northern ends, respectively, of magnetic flux tubes that had been excited in some way by the proximity of fragments Q2 and Q1. In addition to the monitoring of the decametric radiation, a search was conducted for possible comet-enhanced Jovian synchrotron radiation at 45 MHz using a large dipole antenna array at the observatory in Chile. This frequency is above the cutoff of the decametric radiation, but is considerably below the lowest frequency at which the synchrotron emission has previously been detected. The minimum detectable flux density with the 45 MHz antenna was about 5 Jy. No synchrotron emission at all was found before, during, or after the entry of the comet fragments. [ABSTRACT FROM AUTHOR]

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Bone marrow transplantation (BMT) is increasingly used in an attempt to correct inborn errors of metabolism (IEM). However, little is known about effects of BMT from patients with IEM donating for non-affected recipients. We present data from a 8.5-year-old girl who underwent BMT in second remission for relapsed acute lymphoblastic leukaemia (ALL) at the age of 7 years from her HLA-identical brother who was severely affected by Hunter syndrome (Mucopolysaccharidosis type II, iduronate-2-sulphatase (IDS) deficiency). After BMT not only leukocyte but also plasma activity of IDS was absent. Mixing experiments and immunoadsorption suggest antibody-mediated enzyme inhibition. However, her urinary glycosaminoglycan excretion has not increased post BMT and clinical signs of mucopolysaccharidosis are absent 20 months after BMT. We conclude that patients with white cell enzyme deficiencies and other IEMs do not have to be excluded from bone marrow donation. Antibody production by the graft may occur and be reflected by a marked reduction in plasma enzyme levels but not tissue activity. Similar antibody responses resulting in enzyme inactivation might also affect other enzyme replacement strategies for individuals with IEM. Bone Marrow Transplantation (2000) 25, 909–911. [ABSTRACT FROM AUTHOR]

We report the case of a 10-year-old boy with congenital pure red cell aplasia (Diamond–Blackfan anaemia) who received an allogeneic bone marrow transplant (BMT) from his HLA-identical sister. The transplant was complicated by moderate veno-occlusive disease (VOD). Despite cytogenetic evidence of complete donor haemopoietic stem cell engraftment there was selective failure of red cell engraftment and he remains red cell transfusion-dependent. This is the first case of a stem cell transplant failing to correct the defect in this condition despite engraftment. [ABSTRACT FROM AUTHOR]

The desire to improve the performance of gas turbine engines has led to higher operating temperatures in the turbine sections of the engine. Materials used for hot section turbine blades and vanes are not resistant to hot corrosion, and therefore require protective coatings. This paper reviews the current art and technology of thermally sprayed MCrAlY and TB coatings onto hot section components. The issues in applying such coatings will be discussed, along with references to manufacturing issues on the shop floor. The difficulties inherent in applying a line-of-sight coating to complex geometries will be discussed. The testing, evaluation, and performance characteristics of typical coatings are discussed. [ABSTRACT FROM AUTHOR]

A monoclonal antibody (RBU/01) was raised against human thyroglobulin and its suitability for the immunohistochemical staining of thyroglobulin was determined on fixed, wax-embedded tissue, using the peroxidase anti-peroxidase (PAP) method. The antibody was then used to demonstrate the expression of human thyroglobulin in sections of a human follicular carcinoma of the thyroid which had been grown in immunodeficient mice. It is concluded that the immunohistochemical evaluation of the xenografts with the antibody provides useful information on this xenograft system as a potential model for thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Liquid biopsies offer the potential to monitor cancer response and resistance to therapeutics in near real-time. However, the plasma cell free DNA (cfDNA) level can be low and the fraction of circulating tumour DNA (ctDNA) bearing a mutation – lower still. Detection of tumour-derived mutations in ctDNA is thus challenging and requires highly sensitive and specific assays. Droplet digital PCR (ddPCR) is a technique that enables exquisitely sensitive detection and quantification of DNA/RNA markers from very limiting clinical samples, including plasma. The Bio-Rad QX200 ddPCR system provides absolute quantitation of target DNA molecules using fluorescent dual-labelled probes. Critical to accurate sample analysis are validated assays that are highly specific, reproducible, and with known performance characteristics, especially with respect to false positives. We present a systematic approach to the development and optimisation of singleplex and multiplex ddPCR assays for the detection of point mutations with a focus on ensuring extremely low false positives whilst retaining high sensitivity. We also present a refined method to determine cfDNA extraction efficiency allowing for more accurate extrapolation of mutational levels in source samples. We have applied these approaches to successfully analyse many ctDNA samples from multiple clinical studies and generated exploratory data of high quality. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor on bone marrow transplantation.