Paul A. Price

BEAMING IN GAMMA-RAY BURSTS: EVIDENCE FOR A STANDARD ENERGY RESERVOIR

We present a comprehensive sample of all gamma-ray burst (GRB) afterglows with known distances, and we derive their conical opening angles based on observed broadband breaks in their light curves. Within the framework of this conical jet model, we correct for the geometry and we find that the gamma-ray energy release is narrowly clustered around 5 × 10^(50) ergs. We draw three conclusions. First, the central engines of GRBs release energies that are comparable to ordinary supernovae. Second, the broad distribution in fluence and luminosity for GRBs is largely the result of a wide variation of opening angles. Third, only a small fraction of GRBs are visible to a given observer, and the true GRB rate is several hundred times larger than the observed rate.

New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease.

gamma-Carboxyglutamic acid-containing protein of bone (BGP) is an abundant noncollagenous protein of mammalian bone. BGP has a molecular weight of 5,800 and contains three residues of the vitamin K-dependent amino acid, gamma-carboxyglutamic acid. We have applied a radioimmunoassay based on calf BGP for the measurement of the protein in the plasma of 109 normal humans and 112 patients with various bone diseases. BGP in human plasma was demonstrated to be indistinguishable from calf BGP by assay dilution studies and gel permeation chromatography. The mean (+/- SE) concentration of BGP in normal subjects was 6.78 (+/- 0.20) ng/ml, 7.89 (+/- 0.32) for males and 4.85 (+/- 0.35) for females. Plasma BGP was increased in patients with Pagets disease of bone, bone metastases, primary hyperparathyroidism, renal osteodystrophy, and osteopenia. Plasma BGP did correlate with plasma alkaline phosphatase (AP) in some instances, but there were dissociations between the two. It was additionally observed that patients with liver disease had normal plasma BGP despite increased plasma AP, a reflection of the lack of specificity of AP measurements for bone disease. Our studies indicate that the radioimmunoassay of plasma BGP can be a useful and specific procedure for evaluating the patient with bone disease.

Warfarin Causes Rapid Calcification of the Elastic Lamellae in Rat Arteries and Heart Valves

High doses of warfarin cause focal calcification of the elastic lamellae in the media of major arteries and in aortic heart valves in the rat. Aortic calcification was first seen after 2 weeks of warfarin treatment and progressively increased in density at 3, 4, and 5 weeks of treatment. By 5 weeks, the highly focal calcification of major arteries could be seen on radiographs and by visual inspection of the artery. The calcification of arteries induced by warfarin is similar to that seen in the matrix Gla protein (MGP)-deficient mouse, which suggests that warfarin induces artery calcification by inhibiting gamma-carboxylation of MGP and thereby inactivating the putative calcification-inhibitory activity of the protein. Warfarin treatment markedly increased the levels of MGP mRNA and protein in calcifying arteries and decreased the level of MGP in serum. Warfarin treatment did not affect bone growth, overall weight gain, or serum calcium and phosphorus levels, and, because of the concurrent administration of vitamin K, prothrombin times and hematocrits were normal. The results indicate that the improved warfarin plus vitamin K treatment protocol developed in this study should provide a useful model to investigate the role of MGP in preventing calcification of arteries and heart valves.

Relativistic ejecta from X-ray flash XRF 060218 and the rate of cosmic explosions

Over the past decade, long-duration γ-ray bursts (GRBs)—including the subclass of X-ray flashes (XRFs)—have been revealed to be a rare variety of type Ibc supernova. Although all these events result from the death of massive stars, the electromagnetic luminosities of GRBs and XRFs exceed those of ordinary type Ibc supernovae by many orders of magnitude. The essential physical process that causes a dying star to produce a GRB or XRF, and not just a supernova, is still unknown. Here we report radio and X-ray observations of XRF 060218 (associated with supernova SN 2006aj), the second-nearest GRB identified until now. We show that this event is a hundred times less energetic but ten times more common than cosmological GRBs. Moreover, it is distinguished from ordinary type Ibc supernovae by the presence of 1048 erg coupled to mildly relativistic ejecta, along with a central engine (an accretion-fed, rapidly rotating compact source) that produces X-rays for weeks after the explosion. This suggests that the production of relativistic ejecta is the key physical distinction between GRBs or XRFs and ordinary supernovae, while the nature of the central engine (black hole or magnetar) may distinguish typical bursts from low-luminosity, spherical events like XRF 060218.

Matrix Gla protein, a new γ-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone

A new protein has been isolated from CaCl2/urea extracts of demineralized bovine bone matrix. This protein has five to six residues of the vitamin K-dependent amino acid, gamma-carboxyglutamic acid (Gla), and we have accordingly designated it matrix Gla protein. Matrix Gla protein is a 15,000 dalton protein whose amino acid composition includes a single disulfide bond. The absence of 4-hydroxyproline in matrix Gla protein demonstrates that it is not a precursor to bone Gla protein, 5,800 dalton protein which has a residue of 4-hydroxyproline at position 9 in its sequence. Matrix Gla protein also does not cross-react with antibodies raised against bone Gla protein.

Disaggregation of bone into crystals.

SummaryThe sizes, shapes, and organizational states of the crystals in bone are studied by systematic disaggregation of the mineral phase. This is achieved by oxidizing the organic phase with sodium hypochlorite, dispersing the resultant particles by sonication, and separating the crystal aggregates from the crystal monomers by gravity setting in ethanol. Six different bones are compared. Bones in which crystals are intimately associated with the collagen fibrils mostly disaggregate into crystal monomers. In dense bones, where the crystals are mostly located between fibrils, they tend to persist as “fused” aggregates. All the crystals are tabular or plate-shaped. In bones in which the majority of crystals are associated with the collagen fibrils, just less than 90% of the crystals are shorter than about 450 Å in length. Their widths are on the average about 250 Å, almost an order of magnitude larger than the diameters of individual gap regions within the collagen fibril. The notion that one crystal is located in one gap region is therefore untenable and a reevaluation of the relations between collagen and mineral in bone is necessary.

Bisphosphonates Alendronate and Ibandronate Inhibit Artery Calcification at Doses Comparable to Those That Inhibit Bone Resorption

Abstract—The present experiments were carried out to test the hypothesis that artery calcification is linked to bone resorption by determining whether the selective inhibition of bone resorption with the bisphosphonates alendronate and ibandronate will inhibit artery calcification. Artery calcification was first induced by treatment of 42-day-old male rats with warfarin, a procedure that inhibits the &ggr;-carboxylation of matrix Gla protein and has been shown to cause extensive calcification of the artery media within 2 weeks. These experiments revealed that ibandronate (0.05 mg · kg−1 · d−1) and alendronate (0.1 mg · kg−1 · d−1) completely inhibited calcification of all arteries and heart valves examined after 2 and 4 weeks of warfarin treatment. A 10-fold lower dose of alendronate reduced artery calcification by 50% (P <0.005). These bisphosphonate doses are comparable to those that inhibit bone resorption in rats of this age. More rapid artery calcification was induced by treatment with warfarin together with high doses of vitamin D, a procedure that causes extensive artery calcification by 84 hours. Alendronate and ibandronate again completely inhibited calcification of all arteries and heart valves examined. The subcutaneous doses of alendronate and ibandronate necessary to inhibit artery calcification are comparable to the daily subcutaneous doses of these drugs that have previously been shown to inhibit bone resorption in rats of the same age, with 50% inhibition of artery calcification at 20 &mgr;g alendronate · kg−1 · d−1 and at 1 &mgr;g ibandronate · kg−1 · d−1. Bisphosphonate treatment did not affect serum calcium and phosphate, and so the inhibition of artery calcification cannot be due to a simple lowering of the serum calcium phosphate ion product. We conclude that bisphosphonates inhibit the calcification of arteries and heart valves at doses comparable to the doses that inhibit bone resorption. These results support the hypothesis that artery calcification is linked to bone resorption. The mechanism of this linkage remains to be established, however, and an alternative explanation for the present results is also considered.

The afterglow and elliptical host galaxy of the short gamma-ray burst GRB 050724.

Despite a rich phenomenology, γ-ray bursts (GRBs) are divided into two classes based on their duration and spectral hardness—the long-soft and the short-hard bursts. The discovery of afterglow emission from long GRBs was a watershed event, pinpointing their origin to star-forming galaxies, and hence the death of massive stars, and indicating an energy release of about 1051 erg. While theoretical arguments suggest that short GRBs are produced in the coalescence of binary compact objects (neutron stars or black holes), the progenitors, energetics and environments of these events remain elusive despite recent localizations. Here we report the discovery of the first radio afterglow from the short burst GRB 050724, which unambiguously associates it with an elliptical galaxy at a redshift z = 0.257. We show that the burst is powered by the same relativistic fireball mechanism as long GRBs, with the ejecta possibly collimated in jets, but that the total energy release is 10–1,000 times smaller. More importantly, the nature of the host galaxy demonstrates that short GRBs arise from an old (> 1 Gyr) stellar population, strengthening earlier suggestions and providing support for coalescing compact object binaries as the progenitors.

Vitamin K-Dependent Formation of Bone Gla Protein (Osteocalcin) and Its Function

Publisher Summary This chapter discusses the vitamin K–dependent formation of bone γ-carboxyglutamic acid (Gla) protein (BGP, osteocalcin) and its function. The bone Gla protein (BGP, osteocalcin) is the best characterized noncollagenous bone protein. Characteristic chemical features are small size—typically 49 or 50 residues—and existence within the molecule of three residues of the vitamin K–dependent amino acid, Gla. BGP is among the most abundant noncollagenous bone proteins and appears to be a universal constituent of the skeleton and tooth dentin of all vertebrates. As its synthesis is regulated by 1,25-dihydroxyvitamin D 3 , it is likely that BGP plays a role in the action of this hormone on bone. BGP has been detected in the calcified tissues of all vertebrates examined to date. The molecular weights of calf and chicken BGP have been determined by sedimentation equilibrium centrifugation and are 5800 and 6500, respectively. Both molecular weight values agree well with those computed from the corresponding covalent structures. In contrast, the apparent molecular weight of BGP determined by gel filtration and by SDS-gel electrophoresis is about 12,000.

Serum YKL-40, A New Prognostic Biomarker in Cancer Patients?

YKL-40, a member of the “mammalian chitinase–like proteins,” is expressed and secreted by several types of solid tumors. The exact function of YKL-40 in cancer diseases is unknown and is an important objective of future studies. YKL-40 exhibits growth factor activity for cells involved in tissue remodeling processes. YKL-40 may have a role in cancer cell proliferation, survival, and invasiveness, in the inflammatory process around the tumor, angiogenesis, and remodeling of the extracellular matrix. YKL-40 is neither organ- nor tumor-specific. However, the present retrospective clinical studies of patients with eight different types of primary or advanced solid tumors suggest that serum concentration of YKL-40 may be a new biomarker in cancer patients used as a “prognosticator.” Elevated serum YKL-40 is found in a subgroup of patients with different types of solid tumors, including several types of adenocarcinomas, small cell lung carcinoma, glioblastoma, and melanoma. The highest serum YKL-40 is detected in patients with advanced cancer and with the poorest prognosis. In many cases, serum YKL-40 provides independent information of survival. Serum YKL-40 cannot be used as a single screening test for cancer. The use of serum YKL-40 has not received Food and Drug Administration approval for use as a biomarker for cancer or any other disease. Large multicenter retrospective and prospective studies of patients with different types of cancer are required to determine: (a) if serum YKL-40 is a useful prognostic cancer biomarker, (b) if serum YKL-40 can be of value in monitoring patients with cancer in order to provide information about metastases before these are detected by routine methods, and (c) if serum YKL-40 can be useful for screening of cancer together with a panel of other cancer biomarkers and imaging techniques. (Cancer Epidemiol Biomarkers Prev 2006;15(2):194–202)