We investigated patterns of within-species genetic variation for traits observed in hybrids (hybrid numbers, hybrid sex ratios, and hybrid male deformities) between two species of flour beetles, ...Tribolium castaneum and T. freemani. We found genetic variation segregating among four natural populations of T. castaneum as well as within these populations. For some hybrid traits, we observed as much variation among populations 750 km apart as between populations on different continents, suggesting genetic differentiation at a local scale. Within natural populations, the variation segregating among sires is greater than that found in an earlier study for an outbred laboratory population and comparable to that observed between inbred lines derived from the outbred stock by eight generations of brother-sister mating. When sires from T. castaneum are mated to conspecific and heterospecific females, we do not observe a significant correlation at the level of the family mean between the intraspecific and interspecific phenotypes, suggesting the independence of the hybrid traits from comparable traits within species. We discuss our findings in relation to the evolutionary genetics of speciation and the expression of epistatic genetic variance in interspecific crosses.
The aim of this study was to estimate the incidence of complications after (90)Y microsphere radioembolization for unresectable hepatic tumors and evaluate risk factors for late complications.
A ...cohort of 112 consecutive patients from two institutions underwent (90)Y microsphere radioembolization for unresectable hepatic tumors. Complications were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Symptoms secondary to postradioembolization syndrome occurring within 30 days were recorded as early complications, and all other complications were considered late complications.
Seventy-eight patients (70%) experienced postradioembolization syndrome, including fatigue, abdominal pain, nausea, vomiting, anorexia, or fever. Three patients (3%) experienced a Grade 3 early complication; no Grade 4 or 5 early toxicity occurred. Two patients (2%) experienced clinically significant liver dysfunction; 13 patients (12%), 27 patients (24%), and 9 patients (8%) had an elevation of bilirubin, aspartate aminotransferase, and alanine aminotransferase, respectively. Eleven patients (10%) experienced gastrointestinal ulceration, including two Grade 3 complications and one Grade 4 complication. Cholecystitis occurred in 7 patients (6%), including two Grade 3 complications. Grade 2 pancreatitis occurred in 1 patient (1%). No radiation pneumonitis was observed. The cumulative incidence of late Grade 3 or 4 complications at 12 months after radioembolization was 8%. No Grade 5 toxicity occurred.
(90)Y microsphere radioembolization is a well-tolerated treatment for unresectable hepatic tumors with a low risk of Grade 3 or higher early or late toxicity.
Is Digital Different? Dupuis, Marc J; Moss, Michael S; Endicott-Popovsky, Barbara
01/2017
eBook
This edited collection brings together global experts to explore the role of information professionals in the transition from an analogue to a digital environment.The contributors, including David ...Nicholas, Valerie Johnson, Tim Gollins and Scott David, focus on the opportunities and challenges afforded by this new environment that is transforming the information landscape in ways that were scarcely imaginable a decade ago and is challenging the very existence of the traditional library and archive as more and more resources become available on line and as computers and supporting networks become more and more powerful. By drawing on examples of the impact of other new and emerging technologies on the information sciences in the past, the book emphasises that information systems have always been shaped by available technologies that have transformed the creation, capture, preservation and discovery of content.
Torsional energies for rotation of an aglycon depend on the
exo-anomeric conformation.
The rotational barrier for a methyl group at the end of an anomeric system is sometimes lower than we might have ...anticipated. Thus, in the
trans–trans conformation of dimethoxymethane, the barrier to methyl rotation is calculated (B3LYP/6-311++G(2d,2p)) to be 2.22
kcal/mol, just slightly smaller than the corresponding barrier to rotation of the methyl group in methyl propyl ether of 2.32
kcal/mol. However, if the methyl being rotated in dimethoxymethane is placed into a
gauche conformation, that rotational barrier is reduced to 1.52
kcal/mol. This substantial (0.80
kcal/mol relative to methyl propyl ether) reduction in barrier height in the latter case is attributed mainly to the change in the bond order of the C–O bond to which the methyl is attached, as a function of conformation, which in turn is a result of the anomeric effect. We have called this barrier lowering the
external-anomeric torsional effect. This effect is apparently widespread in carbohydrates, and it results in the changing of conformational energies by up to about 2
kcal/mol. If polysaccharide potential surfaces are to be accurately mapped by molecular mechanics, this effect clearly needs to be accounted for.
Loss of E-cadherin (CDH1) function is thought to contribute to progression in breast cancer and other solid tumors by increasing proliferation, invasion, and/or metastasis. In some cases, the ...restoration of CDH1 function may be an important therapeutic option. This possibility will depend on the mechanism by which CDH1 is inactivated. Here we present analyses of CDH1 expression, genetic mutation, and promoter methylation in CDH1 in 10 commonly used breast cancer cell lines. Five cell lines (BT-474, MCF-7, MDA-MB-361, MDA-MB-468, and T-47D) expressed CDH1 and were genetically normal. Five others (SK-BR-3, 600 MPE, MDA-MB-134 IV, CAMA1, and MDA-MB-435) did not express CDH1. Fluorescence in situ hybridization analyses of each of these cell lines showed evidence for the physical deletion of one allele of CDH1, and three cell lines were found to carry homozygous deletions. SK-BR-3 was deleted from exon 12 through the promoter; exon 6 was deleted in MDA-MB-134 IV cells, and 600 MPE cells carried a 21-bp deletion in the splicing acceptor site for exon 9. CAMA1 seemed to have been inactivated through promoter methylation. No explanation was found for the inactivation of CDH1 in MDA-MB-435.
Long-acting formulations of recombinant human growth hormone (rhGH) were prepared by stabilizing and encapsulating the protein into three different injectable, biodegradable microsphere formulations ...composed of polymers of lactic and glycolic acid. The formulations were compared in juvenile rhesus monkeys by measuring the serum levels of rhGH and two proteins induced by hGH, insulin-like growth factor-I and IGF binding protein-3 (IGFBP-3) after single s.c. administration. All three formulations, which differed principally in the composition of the polymer, provided sustained elevated levels of all three proteins for several weeks, and the rate of release of rhGH differed among the formulations consistent with the molecular weight of the polymer used. All three formulations induced a higher level of insulin-like growth factor-I and insulin-like growth factor binding protein than was induced by daily injections of the same amount of rhGH in solution. After three monthly injections of one of the formulations, both the rhGH and IGF-I levels remained elevated for nearly 90 days. Immunogenicity of the rhGH released from this formulation, as assessed by the incidence of seroconversion to hGH and the titer of anti-hGH antibody in both the rhesus monkeys and transgenic mice expressing rhGH, was no greater than that of the unencapsulated protein. In addition, the microsphere injection sites appeared normal by macroscopic evaluation between 1 to 2 mo after microsphere administration and by microscopic evaluation between 2 to 3 mo. These results show that serum levels of a therapeutic protein can be sustained for an extended period when encapsulated into different formulations of injectable, biodegradable microspheres.
We report the discovery of chroman 28, a potent and selective antagonist of human, nonhuman primate, rat, and rabbit bradykinin B1 receptors (0.4−17 nM). At 90 mg/kg s.c., 28 decreased plasma ...extravasation in two rodent models of inflammation. A novel method to calculate entropy is introduced and ascribed ∼30% of the gained affinity between “flexible” 4 (K i = 132 nM) and “rigid” 28 (K i = 0.77 nM) to decreased conformational entropy.
OBJECTIVE--To investigate the prevalence of Mycobacterium tuberculosis DNA in granulomatous tissues from patients with sarcoidosis and from controls matched for age, sex, and tissue by using the ...polymerase chain reaction. DESIGN--Single blind control trial. SUBJECTS--16 patients with sarcoidosis who had undergone diagnostic biopsy of lung, skin, or lymph node and 16 patients with squamous cell carcinoma or Hodgkin's disease to act as controls. In addition, four lung specimens infected with M tuberculosis were included as positive controls. RESULTS--M tuberculosis DNA was present in sarcoid tissues containing granulomas from seven of the 16 patients and one of the 16 matched controls. Two of the four specimens known to be infected with M tuberculosis were positive in the controlled experiment. CONCLUSION--These figures suggest that M tuberculosis DNA is detected as readily in patients with sarcoidosis as in patients with frankly tuberculous tissues and imply that M tuberculosis may be linked to the cause of sarcoidosis.
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