Thrombopoietin, flt3-ligand and c-kit-ligand modulate HOX gene expression in expanding cord blood CD133(+) cells

Haemopoietic stem/progenitor cell (HSPC) development is regulated by extrinsic and intrinsic stimuli. Extrinsic modulators include growth factors and cell adhesion molecules, whereas intrinsic regulation is achieved with many transcription factor families, of which the HOX gene products are known to be important in haemopoiesis. Umbilical cord blood CD133(+) HSPC proliferation potential was tested in liquid culture with 'TPOFLK' (thrombopoietin, flt-3 ligand and c-kit ligand, promoting HSPC survival and self-renewal), in comparison to 'K36EG' (c-kit-ligand, interleukins-3 and -6, erythropoietin and granulocyte colony-stimulating factor, inducing haemopoietic differentiation). TPOFLK induced a higher CD133(+) HSPC proliferation (up to 60-fold more, at week 8) and maintained a higher frequency of the primitive colony-forming cells than K36EG. Quantitative polymerase chain reaction analysis revealed opposite expression patterns for specific HOX genes in expanding cord blood CD133(+) HSPC. After 8 weeks in liquid culture, TPOFLK increased the expression of HOX B3, B4 and A9 (associated with uncommitted HSPC) and reduced the expression of HOX B8 and A10 (expressed in committed myeloid cells) when compared to K36EG. These results suggest that TPOFLK induces CD133(+) HSPC proliferation, self-renewal and maintenance, up-regulation of HOX B3, B4 and A9 and down-regulation of HOX B8 and A10 gene expression.

The NAD(P)H : quinone oxidoreductase IC609T polymorphism modifies the risk of Barrett esophagus and esophageal adenocarcinoma

Purpose: The role of genetic susceptibility to esophageal adenocarcinorna and its precursor lesion Barrett esophagus has not been fully elucidated. This study investigated the effect of polymorphisms in the manganese superoxide dismutase (MnSOD) and NAD(P)H:quinone oxicloreductase 1 (NQO1) genes in modulating the risk of developing Barrett esophagus or esophageal adenocarcinoma. Methods: A total of 584 patients (146 esophagitis, 200 Barrett esophagus, 144 esophageal adenocarcinoma, and 94 controls) were genotyped for the MnSOD C14T and NQO1 C609T polymorphisms using polymerase chain reaction and restriction fragment length polymorphism analysis. Results: The NQO1 TT genotype was less common in Barrett esophagus (2.0%) and esophageal adenocarcinoma (1.4%) patients, compared with both esophagitis patients (7.6%) and controls (5.4%). After adjustment for sex, age, body mass index, reflux symptoms, and smoking status, patients with the homozygous TT genotype had a 4.5-fold decreased risk of developing Barrett esophagus (odds ratio = 0.22, 95% confidence interval = 0.07-0.76, P = 0.01) and a 6.2-fold decreased risk of esophageal adenocarcinorna (odds ratio = 0.16, 95% confidence intervals = 0.03-0.94, P = 0.04) compared with individuals with the TC and CC genotypes. No significant differences between groups were observed for the MnSOD polymorphism (P = 0.289). Conclusions: Overall, the results of this study suggest that the NQO1 TT genotype may offer protection from reflux complications such as Barrett esophagus and esophageal adenocarcinoma.

An R -matrix with pseudo-states calculation of electron-impact excitation in C 2 +

We have performed an R-matrix with pseudo-states (RMPS) calculation of electron-impact excitation in C2+.Collision strengths and effective collision strengths were determined for excitation between the lowest 24 terms, including all those arising from the 2s3l and 2s4l configurations. In the RMPS calculation, 238 terms (90 spectroscopic and 148 pseudo-state) were employed in the close-coupling (CC) expansion of the target. In order to investigate the significance of coupling to the target continuum and highly excited bound states, we compare the RMPS results with those from an R-matrix calculation that incorporated all 238 terms in the configuration- interaction expansion, but only the lowest 44 spectroscopic terms in the CC expansion. We also compare our effective collision strengths with those from an earlier 12-state R-matrix calculation (Berrington et al 1989 J. Phys. B: At.Mol. Opt. Phys. 22 665). The RMPS calculation was extremely large, involving (N +1)-electron Hamiltonian matrices of dimension up to 36 085, and required the use of our recently completed suite of parallel R-matrix programs. The full set of effective collision strengths fromourRMPS calculation is available at theOakRidgeNationalLaboratoryControlledFusion Atomic Data Center web site. 1.

Electron-impact ionization of the C atom

Time-dependent close-coupling (TDCC), R-matrix-with-pseudostates (RMPS), and time-independent distorted-wave (TIDW) methods are used to calculate electron-impact ionization cross sections for the carbon atom. The TDCC and RMPS results for the 1s22s22p2 ground configuration are in reasonable agreement with the available experimental measurements, while the TIDW results are 30% higher. Ionization of the 1s22s2p3 excited configuration is performed using the TDCC, RMPS, and TIDW methods. Ionization of the 1s22s22p3l (l=0–2) excited configurations is performed using the TDCC and TIDW methods. The ionization cross sections for the excited configurations are much larger than for the ground state. For example, the peak cross section for the 1s22s22p3p excited configuration is an order of magnitude larger than the peak cross section for the 1s22s22p2 ground configuration. The TDCC results are again found to be substantially lower than the TIDW results. The ionization cross-section results will permit the generation of more accurate, generalized collisional-radiative ionization coefficients needed for modeling moderately dense carbon plasmas.

Electron-impact ionization of C+ in both ground and metastable states

Electron-impact ionization cross sections are calculated for the ground and metastable states of C+. Com- parisons between perturbative distorted-wave and nonperturbative time-dependent close-coupling calculations find reductions in the peak direct ionization cross sections due to electron coupling effects of approximately 5% for ground state C+ and approximately 15% for metastable state C+. Fairly small excitation-autoionization contributions are found for ground state C+, while larger excitation-autoionization contributions are found for metastable state C+. Comparisons between perturbative distorted-wave and nonperturbative R-matrix with pseudostates calculations find reductions in the peak total ionization cross sections due to electron coupling effects of approximately 15–20 % for ground state C+ and approximately 25–35 % for metastable state C+. Finally, comparisons between theory and experiment find that present and previous C+ crossed-beam measure- ments are in excellent agreement with ground state nonperturbative R-matrix with pseudostates calculations for total ionization cross sections. Combined with previous non-perturbative calculations for C, C2+, and C3+, accurate ionization cross sections and rate coefficients are now available for the ground and metastable states of all carbon ion stages.

Generalized collisional radiative model for light elements: C: Data for the B isonuclear sequence

A first stage collision database is assembled which contains electron-impact excitation, ionization,\r and recombination rate coefficients for B, B + , B 2+ , B 3+ , and B 4+ . The first stage database\r is constructed using the R-matrix with pseudostates, time-dependent close-coupling, and perturbative\r distorted-wave methods. A second stage collision database is then assembled which contains\r generalized collisional-radiative ionization, recombination, and power loss rate coefficients as a\r function of both temperature and density. The second stage database is constructed by solution of\r the collisional-radiative equations in the quasi-static equilibrium approximation using the first\r stage database. Both collision database stages reside in electronic form at the IAEA Labeled Atomic\r Data Interface (ALADDIN) database and the Atomic Data Analysis Structure (ADAS) open database.

Direction repulsion goes global

When viewing two superimposed, translating sets of dots moving in different directions, one overestimates the direction difference. This phenomenon of direction repulsion is thought to be driven by inhibitory interactions between directionally tuned motion detectors [1, 2]. However, there is disagreement on where this occurs — at early stages of motion processing [1, 3], or at the later, global motion-processing stage following “pooling” of these measures [4–6]. These two stages of motion pro - cessing have been identified as occurring in area V1 and the human homolog of macaque MT/V5, respectively[7, 8]. We designed experiments in which local and global predictions of repulsion are pitted against one another. Our stimuli contained a target set of dots, moving at a uniform speed, superimposed on a “mixed-speed” distractor set. Because the perceived speed of a mixed-speed stimulus is equal to the dots’ average speed [9], a global-processing account of direction repulsion predicts that repulsion magnitude induced by a mixed-speed distractor will be indistinguishable from that induced by a single-speed distractor moving at the same mean speed. This is exactly what we found. These results provide compelling evidence that global-motion interactions play a major role in driving direction repulsion.

Speed tuning of direction repulsion describes an inverted U-function

Direction repulsion describes the phenomenon in which observers typically overestimate the direction difference between two superimposed motions moving in different directions (Marshak & Sekuler, Science 205(1979) 1399). Previous research has found that, when a relatively narrow range of distractor speeds is considered, direction repulsion of a target motion increases monotonically with increasing speed of the distractor motion. We sought to obtain a more complete measurement of this speed-tuning function by considering a wider range of distractor speeds than has previously been used. Our results show that, contrary to previous reports, direction repulsion as a function of distractor speed describes an inverted U-function. For a target of 2.5deg/s, we demonstrate that the attenuation of repulsion magnitude with high-speed disractors can be largely explained in terms of the reduced apparent contrast of the distractor. However, when we reduce target motion speed, this no longer holds. When considered from the perspective of Edwards et al.s (Edwards, Badcock, & Smith, Vision Research 38 (1998) 1573) two global-motion channels, our results suggest that direction repulsion is speed dependent when the distractor and target motions are processed by different globalmotion channels, but is not speed dependent when both motions are processed by the same, high-speed channel. The implications of these results for models of direction repulsion are discussed.

Test stimulus characteristics determine the perceived speed of the dynamic motion aftereffect

Using a speed-matching task, we measured the speed tuning of the dynamic motion aftereVect (MAE). The results of our Wrst experiment, in which we co-varied dot speed in the adaptation and test stimuli, revealed a speed tuning function. We sought to tease apart what contribution, if any, the test stimulus makes towards the observed speed tuning. This was examined by independently manipulating dot speed in the adaptation and test stimuli, and measuring the eVect this had on the perceived speed of the dynamic MAE. The results revealed that the speed tuning of the dynamic MAE is determined, not by the speed of the adaptation stimulus, but by the local motion characteristics of the dynamic test stimulus. The role of the test stimulus in determining the perceived speed of the dynamic MAE was conWrmed by showing that, if one uses a test stimulus containing two sources of local speed information, observers report seeing a transparent MAE; this is despite the fact that adaptation is induced using a single-speed stimulus. Thus while the adaptation stimulus necessarily determines perceived direction of the dynamic MAE, its perceived speed is determined by the test stimulus. This dissociation of speed and direction supports the notion that the processing of these two visual attributes may be partially independent.