Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
498
result(s) for
"Heather, P. J. (Peter J.)"
Sort by:
Empires and barbarians : the fall of Rome and the birth of Europe
\"Here is a fresh, provocative look at how a recognizable Europe came into being in the first millennium AD. With sharp analytic insight, Peter Heather explores the dynamics of migration and social and economic interaction that changed two vastly different worlds--the undeveloped barbarian world and the sophisticated Roman Empire--into remarkably similar societies and states. The book's vivid narrative begins at the time of Christ, when the Mediterranean circle, newly united under the Romans, hosted a politically sophisticated, economically advanced, and culturally developed civilization--one with philosophy, banking, professional armies, literature, stunning architecture, even garbage collection. The rest of Europe, meanwhile, was home to subsistence farmers living in small groups, dominated largely by Germanic speakers. Although having some iron tools and weapons, these mostly illiterate peoples worked mainly in wood and never built in stone. The farther east one went, the simpler it became: fewer iron tools and ever less productive economies. And yet ten centuries later, from the Atlantic to the Urals, the European world had turned. Slavic speakers had largely superseded Germanic speakers in central and Eastern Europe, literacy was growing, Christianity had spread, and most fundamentally, Mediterranean supremacy was broken. The emergence of larger and stronger states in the north and east had, by the year 1000, brought patterns of human organization into much greater homogeneity across the continent. Barbarian Europe was barbarian no longer. Bringing the whole of first millennium European history together for the first time, and challenging current arguments that migration played but a tiny role in this unfolding narrative, Empires and Barbarians views the destruction of the ancient world order in the light of modern migration and globalization patterns. The result is a compelling, nuanced, and integrated view of how the foundations of modern Europe were laid\"--Provided by publisher.
Book
molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule
IRE1 couples endoplasmic reticulum unfolded protein load to RNA cleavage events that culminate in the sequence-specific splicing of the Xbp1 mRNA and in the regulated degradation of diverse membrane-bound mRNAs. We report on the identification of a small molecule inhibitor that attains its selectivity by forming an unusually stable Schiff base with lysine 907 in the IRE1 endonuclease domain, explained by solvent inaccessibility of the imine bond in the enzyme-inhibitor complex. The inhibitor (abbreviated 4μ8C) blocks substrate access to the active site of IRE1 and selectively inactivates both Xbp1 splicing and IRE1-mediated mRNA degradation. Surprisingly, inhibition of IRE1 endonuclease activity does not sensitize cells to the consequences of acute endoplasmic reticulum stress, but rather interferes with the expansion of secretory capacity. Thus, the chemical reactivity and sterics of a unique residue in the endonuclease active site of IRE1 can be exploited by selective inhibitors to interfere with protein secretion in pathological settings.
Journal Article
The restoration of Rome : barbarian popes & imperial pretenders
\"In 476 AD, the last of Rome's emperors, known as \"Augustulus\" was deposed by a barbarian general, the son of one of Attila the Hun's henchmen. With the imperial vestments dispatched to Constantinople, the curtain fell on the Roman empire in Western Europe, its territories divided among successor kingdoms constructed around barbarian military manpower. But, if the Roman Empire was dead, Romans across the old empire still lived, holding on to their lands, the values of their civilization, and their institutions. The conquering barbarians, witnessing the continuing psychological dominance of Rome, were ready to reignite the imperial flame and enjoy the benefits of its civilization. As Peter Heather shows in dazzling biographical portraits, each of the three greatest contenders-- Theoderic, Justinian, and Charlemagne-- operated with a different power base but was astonishingly successful in his own way. Though each in turn managed to put back together enough of the old Roman West to stake a plausible claim to the Western imperial title, none of their empires long outlived their founders' deaths. Not until the reinvention of the papacy in the eleventh century would Europe's barbarians find the means to establish a new Roman Empire, one that has lasted a thousand years\"-- Provided by publisher.
Book
The Data Release of the Sloan Digital Sky Survey-II Supernova Survey
This paper describes the data release of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey conducted between 2005 and 2007. Light curves, spectra, classifications, and ancillary data are presented for 10,258 variable and transient sources discovered through repeat ugriz imaging of SDSS Stripe 82, a 300 deg2 area along the celestial equator. This data release is comprised of all transient sources brighter than r 22.5 mag with no history of variability prior to 2004. Dedicated spectroscopic observations were performed on a subset of 889 transients, as well as spectra for thousands of transient host galaxies using the SDSS-III BOSS spectrographs. Photometric classifications are provided for the candidates with good multi-color light curves that were not observed spectroscopically, using host galaxy redshift information when available. From these observations, 4607 transients are either spectroscopically confirmed, or likely to be, supernovae, making this the largest sample of supernova candidates ever compiled. We present a new method for SN host-galaxy identification and derive host-galaxy properties including stellar masses, star formation rates, and the average stellar population ages from our SDSS multi-band photometry. We derive SALT2 distance moduli for a total of 1364 SN Ia with spectroscopic redshifts as well as photometric redshifts for a further 624 purely photometric SN Ia candidates. Using the spectroscopically confirmed subset of the three-year SDSS-II SN Ia sample and assuming a flat ΛCDM cosmology, we determine M = 0.315 0.093 (statistical error only) and detect a non-zero cosmological constant at 5.7 .
Journal Article
Randomized Controlled Trial Evaluating the Use of Zoledronic Acid in Duchenne Muscular Dystrophy
Abstract
Context
Patients with glucocorticoid-dependent Duchenne muscular dystrophy (DMD) have increased fracture risk and reduced bone mineral density (BMD), often precipitating mobility loss.
Objective
To investigate use of zoledronic acid (ZA) in DMD in improving BMD.
Methods
Two arm, parallel, randomized controlled trial, set in pediatric hospitals across Australia and New Zealand. Sixty-two (31 per arm) boys with glucocorticoid-dependent DMD between 6 and 16 years were included. Five ZA infusions (0.025 mg/kg at months 0, and 3, and 0.05 mg/kg at months 6, 12, and 18), plus calcium and vitamin D, were compared with calcium and vitamin D alone. The main outcome measures were change in lumbar spine (LS) BMD raw and Z-score by dual energy absorptiometry x-ray (DXA) at 12 and 24 months, secondary outcomes assessing mobility, fracture incidence, bone turnover, peripheral quantitative computerized (pQCT) and pain scores.
Results
At 12 and 24 months, mean difference in changes of LS BMD Z-score from baseline was 1.2 SD (95% CI 0.9-1.5), higher by 19.3% (14.6-24.0) and 1.4 SD (0.9-1.9), higher by 26.0% (17.4-34.5) in ZA than control arms respectively (both P < .001). Five controls developed Genant 3 vertebral fractures, 0 in the ZA arm. Mobility, pain, and bone turnover markers were similar between arms at 12 and 24 months. Trabecular BMC and vBMD pQCT at radius and tibia were greater at 12 months in the ZA cohort than control; the evidence for this difference remained at 24 months for radius but not tibia.
Conclusion
ZA improved BMD in glucocorticoid-dependent DMD boys. Although the small cohort precluded demonstrable fracture benefit, improved BMD might reduce incident vertebral fracture.
Journal Article
A small-cell lung cancer genome with complex signatures of tobacco exposure
Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3–8 of
CHD7
in frame, and another two lines carrying
PVT1–CHD7
fusion genes, indicating that
CHD7
may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.
Cancer genomes compared
The two cancer genome sequences presented in this issue demonstrate how next-generation sequencing technologies can inform us about mutational processes, repair pathways and gene networks associated with cancer development. First, the genome of a cell line derived from a bone marrow metastasis in a patient who had small-cell lung cancer. This cancer is typical of the type induced by smoking, and the sequence contains mutation signatures characteristic of some of the more than 60 carcinogens present in tobacco smoke. The second paper compares the whole genome sequence of a melanoma cell line to a lymphoblastoid cell line from the same individual. This, the first complete mutational analysis of a solid tumour, reveals a dominant mutational signature reflecting DNA damage due to exposure to ultraviolet light.
Tobacco smoke contains more than sixty carcinogens that bind and mutate DNA. Here, massively parallel sequencing technology is used to sequence a small-cell lung cancer cell line, exploring the mutational burden associated with tobacco smoking. Multiple mutation signatures from the cocktail of carcinogens in tobacco smoke are found, as well as evidence of transcription-coupled repair and another, more general, expression-linked repair pathway.
Journal Article
Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor
The lack of model systems has limited the preclinical discovery and testing of therapies for Wilms tumor (WT) patients who have poor outcomes. Herein, we establish 45 heterotopic WT patient-derived xenografts (WTPDX) in CB17 scid
-/-
mice that capture the biological heterogeneity of Wilms tumor (WT). Among these 45 total WTPDX, 6 from patients with diffuse anaplastic tumors, 9 from patients who experienced disease relapse, and 13 from patients with bilateral disease are included. Early passage WTPDX show evidence of clonal selection, clonal evolution and enrichment of blastemal gene expression. Favorable histology WTPDX are sensitive, whereas unfavorable histology WTPDX are resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin given singly or in combination. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool to test targeted therapies for WT patient groups with poor outcomes.
The progress in pre-clinical drug discovery for Wilms tumor (WT) is limited by a lack of disease models. Here, the authors develop 45 heterotopic WT patient-derived xenografts including several anaplastic models that recapitulate the biological heterogeneity of WT, and propose this as a resource for evaluating future therapeutics for WT.
Journal Article
Behavioral Inhibition: Linking Biology and Behavior within a Developmental Framework
Behavioral inhibition refers to a temperament or style of reacting that some infants and young children exhibit when confronted with novel situations or unfamiliar adults or peers. Research on behavioral inhibition has examined the link between this set of behaviors to the neural systems involved in the experience and expression of fear. There are strong parallels between the physiology of behaviorally inhibited children and the activation of physiological systems associated with conditioned and unconditioned fear. Research has examined which caregiving behaviors support the frequency of behavioral inhibition across development, and work on the interface of cognitive processes and behavioral inhibition reveal both how certain cognitive processes moderate behavioral inhibition and how this temperament affects the development of cognition. This research has taken place within a context of the possibility that stable behavioral inhibition may be a risk factor for psychopathology, particularly anxiety disorders in older children. The current chapter reviews these areas of research and provides an integrative account of the broad impact of behavioral inhibition research.
Journal Article
Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production
Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene
CADM1
. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total,
n
= 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was
CYP11B2
(aldosterone synthase), and biological rhythms were the most differentially expressed process.
CADM1
knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased
CYP11B2
similarly to
CADM1
mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of
CADM1
cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production.
Recurrent somatic mutations altering residues in the transmembrane domain of
CADM1
are identified in aldosterone-producing adenomas. Follow-up studies implicate a role of gap junction communication in regulating aldosterone production.
Journal Article