An increase in N-Ras expression is associated with development of hormone refractory prostate cancer in a subset of patients

Protein expression of H, K and N-Ras was assessed in hormone sensitive and hormone refractory prostate tumour pairs from 61 patients by immunohistochemistry. Expression of H-Ras and K- Ras was not associated with any known clinical parameters. In contrast an increase in N-Ras membrane expression in the transition from hormone sensitive to hormone refractory prostate cancer was associated with shorter time to relapse (p=0.01) and shorter disease specific survival (p=0.008). In addition, patients with an increase in N-Ras membrane expression had lower levels of PSA at relapse (p=0.02) and expression correlated with phosphorylated MAP kinase (p=0.010) and proliferation index (Ki67, p=0.02). These results suggest that in a subgroup patients N-Ras expression is associated with development of hormone refractory prostate cancer via activation of the MAP kinase cascade

Ras/Raf-1/MAPK pathway mediates response to tamoxifen but not chemotherapy in breast cancer patients

<b>Purpose</b>: The expression and activation of the Ras/Raf-1/mitogen-activated protein kinase (MAPK) pathway plays an important role in the development and progression of cancer, and may influence response to treatments such as tamoxifen and chemotherapy. In this study we investigated whether the expression and activation of the key components of this pathway influenced clinical outcome, to test the hypothesis that activation of the MAPK pathway drives resistance to tamoxifen and chemotherapy in women with breast cancer. <b>Experimental Design</b>: Breast tumors from patients at the Glasgow Royal Infirmary and others treated within the BR9601 trial were analyzed for expression of the three Ras isoforms, total Raf-1, active and inactive forms of Raf-1 [pRaf(ser338) and pRaf(ser259), respectively], MAPK, and phospho-MAPK using an immunohistochemical approach. Analyses were done with respect to disease free-survival and overall survival. <b>Results</b>: Expression and activation of the Ras pathway was associated with loss of benefit from treatment with tamoxifen but not chemotherapy. Overexpression of pRaf(ser338) was associated with shortened disease-free and overall survival time in univariate analyses. Multivariate analysis suggested pRaf(ser338) was independent of known prognostic markers in predicting outcome following tamoxifen treatment (<i>P</i>=0.03). <b>Conclusion</b>: This study suggests that activation of the Ras pathway predicts for poor outcome on tamoxifen but not chemotherapy, and identifies pRaf(ser338) as a potential marker of resistance to estrogen receptor–targeted therapy. In addition, it suggests that expression of pRaf(ser338) could identify patients for whom tamoxifen alone is insufficient adjuvant systemic therapy, but for whom the addition of chemotherapy may be of benefit

Influence of previous crops and nematicide treatments on root lesion nematode populations and crop yields

Nous avons étudié au champ l'influence du précédent cultural, de la séquence culturelle et de traitements à l'aldicarbe sur les populations de nematodes des nodosités et sur les rendements de diverses cultures à l'île-du Prince-Édouard. La culture précédente a eu le plus grand impact sur le nombre de nematodes. Les séquences des cultures ont parfois eu une influence sur les populations de nematodes des nodosités (principalement Pratylenchus penetrans) et sur les rendements. Dans les champs commerciaux d'orge (Hordeum vulgare), les nematodes des nodosités étaient plus nombreux lorsque l'orge suivait une culture combinée de trèfle rouge (Trifolium pratense) et de fléole (Phleum pratense) et les nematodes du rabougrissement (Tylenchorynchus spp., principalement T. dubiuset Merlinius spp.) étaient plus nombreux quand l'orge était semée pendant deux années consécutives. La masse de la matière sèche combinée du feuillage et du grain était plus importante lorsque l'orge était semée auprès des pommes de terre (Solanum tuberosum) et cette masse était plus faible avec deux cultures successives d’orge ou avec un mélange de trèfle rouge et de fléole. En conditions expérimentales au champ, les populations de nématodes des nodosités étaient plus élevées dans les racines d’orge lorsque celle-ci était cultivée après des pommes de terre et les rendements en grain étaient plus faibles lorsque l’orge était cultivée pendant deux années consécutives. Les changements dans les populations de nématodes chez la pomme de terre n’étaient pas associés aux séquences débutant avec le blé (Triticum aestivum) ou l’orge que dans les séquences débutant avec les pommes de terre ou le soya (Glycine max). L’aldicarbe a réduit le nombre de nématodes des nodosités en plus d’accroître les rendements en pommes de terre et en soya.A field study assessing the influence of the previous crop, the crop sequence, and aldicarb treatments on root lesion nematode populations and crop yields was carried out in Prince-Edward-Island, Canada. The most recent crop had the greatest impact on nematode numbers. The crop sequences had an influence in some cases on root lesion nematode populations (primarily Pratylenchus penetrans) and on crop yields. In commercial barley (Hordeum vulgare) fields, root lesion nematodes in roots were greatest when barley followed a red clover (Trifolium pratense) timothy (Phleum pratense) ley, and stunt nematodes (Tylenchorhynchus spp., primarily T. dubius, and Merlinius spp.) were more common when barley followed barley. The combined dry weight of foliage and grain was larger when barley was planted after potato (Solanumtuberosum) and smaller when barley followed barley or a red clover-timothy mixture. Under experimental field conditions, root lesion nematode populations were largest in barley roots when barley followed potato and grain yields were smallest when barley followed barley. Changes in nematode populations in potato were not associated with crop sequences. Potato tuber yields were higher in the sequences that began with wheat (Triticum aestivum) or barley than in the sequences that began with potato or soybean (Glycine max). Aldicarb reduced the numbers of root lesion nematodes in roots with concomitant yield increases in potato and soybean

The Long-Term Future of Extragalactic Astronomy

If the current energy density of the universe is indeed dominated by a cosmological constant, then high-redshift sources will remain visible to us only until they reach some finite age in their rest-frame. The radiation emitted beyond that age will never reach us due to the acceleration of the cosmic expansion rate, and so we will never know what these sources look like as they become older. As a source image freezes on a particular time frame along its evolution, its luminosity distance and redshift continue to increase exponentially with observation time. The higher the current redshift of a source is, the younger it will appear as it fades out of sight. For the popular set of cosmological parameters, I show that a source at a redshift z=5-10 will only be visible up to an age of 4-6 billion years. Arguments relating the properties of high-redshift sources to present-day counterparts will remain indirect even if we continue to monitor these sources for an infinite amount of time. These sources will not be visible to us when they reach the current age of the universe.Comment: Phys. Rev. D, in press (2001

Plankton lattices and the role of chaos in plankton patchiness

Spatiotemporal and interspecies irregularities in planktonic populations have been widely observed. Much research into the drivers of such plankton patches has been initiated over the past few decades but only recently have the dynamics of the interacting patches themselves been considered. We take a coupled lattice approach to model continuous-in-time plankton patch dynamics, as opposed to the more common continuum type reaction-diffusion-advection model, because it potentially offers a broader scope of application and numerical study with relative ease. We show that nonsynchronous plankton patch dynamics (the discrete analog of spatiotemporal irregularity) arise quite naturally for patches whose underlying dynamics are chaotic. However, we also observe that for parameters in a neighborhood of the chaotic regime, smooth generalized synchronization of nonidentical patches is more readily supported which reduces the incidence of distinct patchiness. We demonstrate that simply associating the coupling strength with measurements of (effective) turbulent diffusivity results in a realistic critical length of the order of 100 km, above which one would expect to observe unsynchronized behavior. It is likely that this estimate of critical length may be reduced by a more exact interpretation of coupling in turbulent flows

Renal pericytes: regulators of medullary blood flow

Regulation of medullary blood flow (MBF) is essential in maintaining normal kidney function. Blood flow to the medulla is supplied by the descending vasa recta (DVR), which arise from the efferent arterioles of juxtamedullary glomeruli. DVR are composed of a continuous endothelium, intercalated with smooth muscle-like cells called pericytes. Pericytes have been shown to alter the diameter of isolated and in situ DVR in response to vasoactive stimuli that are transmitted via a network of autocrine and paracrine signalling pathways. Vasoactive stimuli can be released by neighbouring tubular epithelial, endothelial, red blood cells and neuronal cells in response to changes in NaCl transport and oxygen tension. The experimentally described sensitivity of pericytes to these stimuli strongly suggests their leading role in the phenomenon of MBF autoregulation. Because the debate on autoregulation of MBF fervently continues, we discuss the evidence favouring a physiological role for pericytes in the regulation of MBF and describe their potential role in tubulo-vascular cross-talk in this region of the kidney. Our review also considers current methods used to explore pericyte activity and function in the renal medulla

Racial/Ethnic and Age Differences in the Direct and Indirect Effects of the COVID-19 Pandemic on US Mortality

Objectives. To estimate the direct and indirect effects of the COVID-19 pandemic on overall, race/ ethnicity-specific, and age-specific mortality in 2020 in the United States. Methods. Using surveillance data, we modeled expected mortality, compared it to observed mortality, and estimated the share of "excess" mortality that was indirectly attributable to the pandemic versus directly attributed to COVID-19. We present absolute risks and proportions of total pandemic-related mortality, stratified by race/ethnicity and age. Results. We observed 16.6 excess deaths per 10 000 US population in 2020; 84% were directly attributed to COVID-19. The indirect effects of the pandemic accounted for 16% of excess mortality, with proportions as low as 0% among adults aged 85 years and older and more than 60% among those aged 15 to 44 years. Indirect causes accounted for a higher proportion of excess mortality among racially minoritized groups (e.g., 32% among Black Americans and 23% among Native Americans) compared with White Americans (11%). Conclusions. The effects of the COVID-19 pandemic on mortality and health disparities are underestimated when only deaths directly attributed to COVID-19 are considered. An equitable public health response to the pandemic should also consider its indirect effects on mortality

Optimizing SARS-CoV-2 Pooled Testing Strategies Through Differentiated Pooling for Distinct Groups

Pooled testing has been successfully used to expand SARS-CoV-2 testing, especially in settings requiring high volumes of screening of lower-risk individuals, but efficiency of pooling declines as prevalence rises. We propose a differentiated pooling strategy that independently optimizes pool sizes for distinct groups with different probabilities of infection to further improve the efficiency of pooled testing. We compared the efficiency (results obtained per test kit used) of the differentiated strategy with a traditional pooling strategy in which all samples are processed using uniform pool sizes under a range of scenarios. For most scenarios, differentiated pooling is more efficient than traditional pooling. In scenarios examined here, an improvement in efficiency of up to 3.94 results per test kit could be obtained through differentiated versus traditional pooling, with more likely scenarios resulting in 0.12 to 0.61 additional results per kit. Under circumstances similar to those observed in a university setting, implementation of our strategy could result in an improvement in efficiency between 0.03 to 3.21 results per test kit. Our results can help identify settings, such as universities and workplaces, where differentiated pooling can conserve critical testing resources

Parity nonconservation in heavy atoms: The radiative correction enhanced by the strong electric field of the nucleus

Parity nonconservation due to the nuclear weak charge is considered. We demonstrate that the radiative corrections to this effect due to the vacuum fluctuations of the characteristic size larger than the nuclear radius $r_0$ and smaller than the electron Compton wave-length $\lambda_C$ are enhanced because of the strong electric field of the nucleus. The parameter that allows one to classify the corrections is the large logarithm $\ln(\lambda_C/r_0)$. The vacuum polarization contribution is enhanced by the second power of the logarithm. Although the self-energy and the vertex corrections do not vanish, they contain only the first power of the logarithm. The value of the radiative correction is 0.4% for Cs and 0.9% for Tl, Pb, and Bi. We discuss also how the correction affects the interpretation of the experimental data on parity nonconservation in atoms.Comment: 4 pages, 3 figures, RevTe

Structure factor of polymers interacting via a short range repulsive potential: application to hairy wormlike micelles

We use the Random Phase Approximation (RPA) to compute the structure factor, S(q), of a solution of chains interacting through a soft and short range repulsive potential V. Above a threshold polymer concentration, whose magnitude is essentially controlled by the range of the potential, S(q) exhibits a peak whose position depends on the concentration. We take advantage of the close analogy between polymers and wormlike micelles and apply our model, using a Gaussian function for V, to quantitatively analyze experimental small angle neutron scattering profiles of semi-dilute solutions of hairy wormlike micelles. These samples, which consist in surfactant self-assembled flexible cylinders decorated by amphiphilic copolymer, provide indeed an appropriate experimental model system to study the structure of sterically interacting polymer solutions