The Lawmaking Congress

General guidelines for understanding how the task of framing and reviewing constitutional issues is approached by senators and representatives in Congress are presented

Developmental gene network analysis

The developmental process is controlled by the information processing functions executed by the cis-elements that regulate the expression of the participating genes. A model of the network of cis-regulatory interactions that underlies the specification of the endomesoderm of the sea urchin embryo is analyzed here. Although not all the relevant interactions have yet been uncovered, the model shows how the information processing functions executed by the cis-regulatory elements involved can control essential functions of the specification process, such as transforming the localization of maternal factors into a domain-specific program of gene expression; refining the specification pattern; and stabilizing states of specification. The analysis suggests that the progressivity of the developmental process is also controlled by the cis-regulatory interactions unraveled by the network model. Given that evolution occurs by changing the program for development of the body plan, we illustrate the potential of developmental gene network analysis in understanding the process by which morphological features are maintained and diversify. Comparison of the network of cis-regulatory interactions with a portion of that underlying the specification of the endomesoderm of the starfish illustrates how the similarities and differences provide insights into how the programs for development work and how they evolve

Competitive titration in living sea urchin embryos of regulatory factors required for expression of the CyIIIa actin gene

Previous studies have located some twenty distinct sites within the 2.3 kb 5' regulatory domain of the sea urchin CyIIIa cytoskeletal actin gene, where there occur in vitro high-specificity interactions with nuclear DNA-binding proteins of the embryo. This gene is activated in late cleavage, exclusively in cells of the aboral ectoderm cell lineages. In this study, we investigate the functional importance in vivo of these sites of DNA-protein interaction. Sea urchin eggs were coinjected with a fusion gene construct in which the bacterial chloramphenicol acetyltransferase (CAT) reporter gene is under the control of the entire CyIIIa regulatory domain, together with molar excesses of one of ten nonoverlapping competitor subfragments of this domain, each of which contains one or a few specific site(s) of interaction. The exogenous excess binding sites competitively titrate the available regulatory factors away from the respective sites associated with the CyIIIa.CAT reporter gene. This provides a method for detecting in vivo sites within the regulatory domain that are required for normal levels of expression, without disturbing the structure of the regulatory domain. We thus identify five nonoverlapping regions of the regulatory DNA that apparently function as binding sites for positively acting transcriptional regulatory factors. Competition with a subfragment bearing an octamer site results in embryonic lethality. We find that three other sites display no quantitative competitive interference with CyIIIa.CAT expression, though as shown in the accompanying paper, two of these sites are required for control of spatial expression. We conclude that the complex CyIIIa regulatory domain must assess the state of many distinct and individually necessary interactions in order to properly regulate CyIIIa transcriptional activity in development

Observations of the Crab Nebula and its pulsar in the far-ultraviolet and in the optical

We present HST/STIS far-UV observations of the Crab nebula and its pulsar. Broad, blueshifted absorption arising in the nebula is seen in C IV 1550, reaching about 2500 km/s. This can be interpreted as evidence for a fast outer shell, and we adopt a spherically symmetric model to constrain the properties of this. We find that the density appears to decrease outward in the shell. A lower limit to the mass is 0.3 solar masses with an accompanying kinetic energy of 1.5EE{49} ergs. A massive 10^{51} erg shell cannot be excluded, but is less likely if the density profile is much steeper than R^{-4} and the velocity is <6000 km/s. The observations cover the region 1140-1720 A. With the time-tag mode of the spectrograph we obtain the pulse profile. It is similar to that in the near-UV, although the primary peak is marginally narrower. Together with the near-UV data, and new optical data from NOT, our spectrum of the pulsar covers the entire region from 1140-9250 A. Dereddening the spectrum gives a flat spectrum for E(B-V)=0.52, R=3.1. This dereddened spectrum of the Crab pulsar can be fitted by a power law with spectral index alpha_{\nu} = 0.11 +/- 0.04. The main uncertainty is the amount and characteristics of the interstel- lar reddening, and we have investigated the dependence of \alpha_{\nu} on E(B-V) and R. In the extended emission covered by our 25" x 0.5" slit in the far-UV, we detect C IV 1550 and He II 1640 emission lines from the Crab nebula. Several interstellar absorption lines are detected toward the pulsar. The Ly alpha absorption indicates a column density of 3.0+/-0.5\EE{21} cm^{-2} of neutral hydrogen, which agrees well with our estimate of E(B-V)=0.52 mag. Other lines show no evidence of severe depletion of metals in atomic gas.Comment: 18 pages emulateapj style, including 10 figures. ApJ, accepte

Fractal dimension (df) as a new structural biomarker of clot microstructure in different stages of lung cancer

Venous thromboembolism (VTE) is common in cancer patients, and is the second commonest cause of death associated with the disease. Patients with chronic inflammation, such as cancer, have been shown to have pathological clot structures with modulated mechanical properties. Fractal dimension (df) is a new technique which has been shown to act as a marker of the microstructure and mechanical properties of blood clots, and can be performed more readily than current methods such as scanning electron microscopy (SEM). We measured df in 87 consecutive patients with newly diagnosed lung cancer prior to treatment and 47 matched-controls. Mean group values were compared for all patients with lung cancer vs controls and for limited disease vs extensive disease. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. Significantly higher values of df were observed in lung cancer patients compared with controls and patients with extensive disease had higher values than those with limited disease (p< 0.05), whilst conventional markers failed to distinguish between these groups. The relationship between df of the incipient clot and mature clot microstructure was confirmed by SEM and computational modelling: higher df was associated with highly dense clots formed of smaller fibrin fibres in lung cancer patients compared to controls. This study demonstrates that df is a sensitive technique which quantifies the structure and mechanical properties of blood clots in patients with lung cancer. Our data suggests that df has the potential to identify patients with an abnormal clot micro-structure and greatest VTE risk