Comparison of CT ventilation imaging and hyperpolarised gas MRI: effects of breathing manoeuvre.

Image registration of lung CT images acquired at different inflation levels has been proposed as a surrogate method to map lung 'ventilation'. Prior to clinical use, it is important to understand how this technique compares with direct ventilation imaging modalities such as hyperpolarised gas MRI. However, variations in lung inflation level have been shown to affect regional ventilation distributions. Therefore, the aim of this study was to evaluate the impact of lung inflation levels when comparing CT ventilation imaging to ventilation from 3He-MRI.
 
 7 asthma patients underwent breath-hold CT at total lung capacity (TLC) and functional residual capacity (FRC). 3He-MRI and a same-breath 1H-MRI were acquired at FRC+1L and TLC. Percentage ventilated volumes (%VVs) were calculated for FRC+1L and TLC 3He-MRI. TLC-CT and registered FRC-CT were used to compute a surrogate ventilation map from voxel-wise intensity differences in Hounsfield unit values, which was thresholded at the 10th and 20th percentiles. For direct comparison of CT and 3He-MRI ventilation, FRC+1L and TLC 3He-MRI were registered to TLC-CT indirectly via the corresponding same-breath 1H-MRI data. For 3He-MRI and CT ventilation comparison, Dice similarity coefficients (DSCs) between the binary segmentations were computed.
 
 The median (range) of %VVs for FRC+1L and TLC 3He-MRI were 90.5 (54.9-93.6) and 91.8 (67.8-96.2), respectively (p=0.018). For MRI versus CT ventilation comparison, statistically significant improvements in DSCs were observed for TLC 3He MRI when compared with FRC+1L, with median (range) values of 0.93 (0.86-0.93) and 0.86 (0.68-0.92), respectively (p=0.017), for the 10-100th percentile and 0.87 (0.83-0.88) and 0.81 (0.66-0.87), respectively (p=0.027), for the 20-100th percentile.
 
 Correlation of CT ventilation imaging and hyperpolarised gas MRI is sensitive to lung inflation level. For ventilation maps derived from CT acquired at FRC and TLC, a higher correlation with gas ventilation MRI can be achieved if the MRI is acquired at TLC. &#13

Motif Discovery through Predictive Modeling of Gene Regulation

We present MEDUSA, an integrative method for learning motif models of transcription factor binding sites by incorporating promoter sequence and gene expression data. We use a modern large-margin machine learning approach, based on boosting, to enable feature selection from the high-dimensional search space of candidate binding sequences while avoiding overfitting. At each iteration of the algorithm, MEDUSA builds a motif model whose presence in the promoter region of a gene, coupled with activity of a regulator in an experiment, is predictive of differential expression. In this way, we learn motifs that are functional and predictive of regulatory response rather than motifs that are simply overrepresented in promoter sequences. Moreover, MEDUSA produces a model of the transcriptional control logic that can predict the expression of any gene in the organism, given the sequence of the promoter region of the target gene and the expression state of a set of known or putative transcription factors and signaling molecules. Each motif model is either a $k$-length sequence, a dimer, or a PSSM that is built by agglomerative probabilistic clustering of sequences with similar boosting loss. By applying MEDUSA to a set of environmental stress response expression data in yeast, we learn motifs whose ability to predict differential expression of target genes outperforms motifs from the TRANSFAC dataset and from a previously published candidate set of PSSMs. We also show that MEDUSA retrieves many experimentally confirmed binding sites associated with environmental stress response from the literature.Comment: RECOMB 200

Upper Pleistocene Stratigraphy, Paleoecology, and Archaeology of the Northern Yukon Interior, Eastern Beringia. I. Bonnet Plume Basin

New stratigraphic and chronometric data show that Bonnet Plume Basin, in northeastern Yukon Territory, was glaciated in late Wisconsinan time rather than during an earlier advance of Laurentide ice. This conclusion has important ramifications not only for the interpretation of all-time glacial limits farther north along the Richardson Mountains but also for non-glaciated basins in the Porcupine drainage to the northwest. The late Wisconsinan glacial episode in Bonnet Plume Basin is here named the Hungry Creek advance after the principal Quaternary section in the basin. Sediments beneath the till at Hungry Creek have produced well-produced pollen, plant macrofossils, insects, and a few vertebrate remains. The plant and invertebrate fossils provide a detailed, if temporally restricted, record of a portion of the mid-Wisconsinan interstadial, while the vertebrate fossils include the oldest Yukon specimen of the Yukon wild ass. Some of the mid-Wisconsinan sediments have also yielded distinctive chert flakes that represent either a previously unreported product of natural fracturing or a by-product of stone tool manufacture by human residents of Bonnet Plume Basin. In addition to presenting new data on these diverse but interrelated topics, this paper serves as an introduction to a series of reports that will treat in turn the Upper Pleistocene record of Bluefish, Old Crow, and Bell basins, respectively.&nbsp

Articular cartilage metabolism in patients with Kashin–Beck Disease: an endemic osteoarthropathy in China

SummaryObjectiveThe objective of this study was to investigate CD44 and proteoglycan metabolism in patients suffering from Kashin–Beck Disease (KBD), an endemic osteoarthropathy that affects 2.5 million of 30 million people living in the KBD regions of China.MethodsImmunohistochemical analyses of cluster of differentiation-44 (CD44), BC-13 and 3-B-3(−) expression were performed in cartilage sections harvested from KBD and normal patients. In addition, the serum levels of soluble CD44 (sCD44), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase-1 were determined using a sandwich enzyme linked immunosorbent assay.ResultsHematoxylin & eosin and toluidine blue staining indicated that there was cell necrosis and proteoglycan loss in cartilage from both KBD children and adult cartilage. Strong immunohistochemical staining for CD44, BC-13 and 3-B-3(−) occurred in the majority of adult KBD patients and most KBD children. Furthermore, statistically significant elevated levels of sCD44, IL-1β and TNF-α were found in the sera of both adult and child KBD patients when compared to the levels of normal adult and child controls. Interestingly, IL-1β and TNF-α serum levels were all high in normal children from KBD regions when compared to normal children from non-KBD regions suggesting that unidentified factors (e.g., a genetic predisposition) may protect some people from KBD pathology.ConclusionOur results demonstrate that altered CD44, IL-1β and TNF-α metabolism occurs in the pathogenesis of KBD and there is an increased aggrecanase-generated proteoglycan loss from KBD adult and child cartilage. These primary metabolic changes are likely to be significant contributing factor causing pathological joint formation and instability that leads to secondary osteoarthritis in KBD patients

The innovation of the symbiosome has enhanced the evolutionary stability of nitrogen fixation in legumes

Nitrogen-fixing symbiosis is globally important in ecosystem functioning and agriculture, yet the evolutionary history of nodulation remains the focus of considerable debate. Recent evidence suggesting a single origin of nodulation followed by massive parallel evolutionary losses raises questions about why a few lineages in the N2-fixing clade retained nodulation and diversified as stable nodulators, while most did not. Within legumes, nodulation is restricted to the two most diverse subfamilies, Papilionoideae and Caesalpinioideae, which show stable retention of nodulation across their core clades. We characterize two nodule anatomy types across 128 species in 56 of the 152 genera of the legume subfamily Caesalpinioideae: fixation thread nodules (FTs), where nitrogen-fixing bacteroids are retained within the apoplast in modified infection threads, and symbiosomes, where rhizobia are symplastically internalized in the host cell cytoplasm within membrane-bound symbiosomes (SYMs). Using a robust phylogenomic tree based on 997 genes from 147 Caesalpinioideae genera, we show that losses of nodulation are more prevalent in lineages with FTs than those with SYMs. We propose that evolution of the symbiosome allows for a more intimate and enduring symbiosis through tighter compartmentalization of their rhizobial microsymbionts, resulting in greater evolutionary stability of nodulation across this species-rich pantropical legume clade

Re-establishment of the genus Pseudalbizzia (Leguminosae, Caesalpinioideae, mimosoid clade): the New World species formerly placed in Albizia

Following recent mimosoid phylogenetic and phylogenomic studies demonstrating the non-monophyly of the genus Albizia, we present a new molecular phylogeny focused on the neotropical species in the genus, with much denser taxon sampling than previous studies. Our aims were to test the monophyly of the neotropical section Arthrosamanea, resolve species relationships, and gain insights into the evolution of fruit morphology. We perform a Bayesian phylogenetic analysis of sequences of nuclear internal and external transcribed spacer regions and trace the evolution of fruit dehiscence and lomentiform pods. Our results find further support for the non-monophyly of the genus Albizia, and confirm the previously proposed segregation of Hesperalbizia, Hydrochorea, Balizia and Pseudosamanea. All species that were sampled from section Arthrosamanea form a clade that is sister to a clade composed of Jupunba, Punjuba, Balizia and Hydrochorea. We find that lomentiform fruits are independently derived from indehiscent septate fruits in both Hydrochorea and section Arthrosamanea. Our results show that morphological adaptations to hydrochory, associated with shifts into seasonally flooded habitats, have occurred several times independently in different geographic areas and different lineages within the ingoid clade. This suggests that environmental conditions have likely played a key role in the evolution of fruit types in Albizia and related genera. We resurrect the name Pseudalbizzia to accommodate the species of section Arthrosamanea, except for two species that were not sampled here but have been shown in other studies to be more closely related to other ingoid genera and we restrict the name Albizia s.s. to the species from Africa, Madagascar, Asia, Australia, and the Pacific. Twenty-one new nomenclatural combinations in Pseudalbizzia are proposed, including 16 species and 5 infraspecific varietal names. In addition to the type species Pseudalbizzia berteroana, the genus has 17 species distributed across tropical regions of the Americas, including the Caribbean. Finally, a new infrageneric classification into five sections is proposed and a distribution map of the species of Pseudalbizzia is presented

A single-center, observational study of 607 children & young people presenting with Differences in Sex Development (DSD)

Context Differences in sex development (DSD) represent a wide range of conditions presenting at different ages to various health professionals. Establishing a diagnosis, supporting the family and developing a management plan are important. Objective We aimed to better understand the presentation and prevalence of pediatric DSD. Design A retrospective, observational cohort study was undertaken of all children and young people (CYP) referred to a DSD multi-disciplinary team over 25 years (1995-2019). Setting A single tertiary paediatric center. Participants In total, 607 CYP (520 regional referrals) were included. Main Outcome Measures Data were analyzed for diagnosis, sex-assignment, age and mode of presentation, additional phenotypic features, mortality, and approximate point prevalence. Results Amongst the three major DSD categories, sex chromosome DSD was diagnosed in 11.2% (68/607) (most commonly 45, X/46, XY mosaicism), 46, XY DSD in 61.1% (371/607) (multiple diagnoses often with associated features), while 46, XX DSD occurred in 27.7% (168/607) (often 21-hydroxylase deficiency). Most children (80.1%) presented as neonates, usually with atypical genitalia, adrenal insufficiency, undescended testes or herniae. Those presenting later had diverse features. Rarely, the diagnosis was made antenatally (3.8%, n = 23) or following incidental karyotyping/family history (n = 14). Mortality was surprisingly high in 46, XY children, usually due to complex associated features (46, XY girls, 8.3%; 46, XY boys, 2.7%). The approximate point prevalence of neonatal referrals for investigation of DSD was 1 in 6,347 births, and 1 in 5,101 overall throughout childhood. Conclusions DSD represent a diverse range of conditions that can present at different ages. Pathways for expert diagnosis and management are important to optimize care

Probing Lorentz and CPT violation with space-based experiments

Space-based experiments offer sensitivity to numerous unmeasured effects involving Lorentz and CPT violation. We provide a classification of clock sensitivities and present explicit expressions for time variations arising in such experiments from nonzero coefficients in the Lorentz- and CPT-violating Standard-Model Extension.Comment: 15 page

The Origins of Bagan: The archaeological landscape of Upper Burma to AD 1300.

The archaeological landscape of Upper Burma from the middle of the first millennium BC to the Bagan period in the 13th-14th century AD is a landscape of continuity. Finds of polished stone and bronze artifacts suggest the existence of early metal-using cultures in the Chindwin and Samon River Valleys, and along parts of the Ayeyarwady plain. Increasing technological and settlement complexity in the Samon Valley suggests that a distinctive culture whose agricultural and trade success can be read in the archaeological record of the Late Prehistoric period developed there. The appearance of the early urban "Pyu" system of walled central places during the early first millennium AD seems to have involved a spread of agricultural and management skills and population from the Samon. The leaders of the urban centres adopted Indic symbols and Sanskrit modes of kingship to enhance and extend their authority. The early urban system was subject over time to a range of stresses including siltation of water systems, external disruption and social changes as Buddhist notions of leadership eclipsed Brahmanical ones. The archaeological evidence indicates that a settlement was forming at Bagan during the last centuries of the first millennium AD. By the mid 11th century Bagan began to dominate Upper Burma, and the region began a transition from a system of largely autonomous city states to a centralised kingdom. Inscriptions of the 11th to 13th centuries indicate that as the Bagan Empire expanded it subsumed the agricultural lands that had been developed by the Pyu