414 research outputs found
Efficient depletion of host DNA contamination in malaria clinical sequencing.
The cost of whole-genome sequencing (WGS) is decreasing rapidly as next-generation sequencing technology continues to advance, and the prospect of making WGS available for public health applications is becoming a reality. So far, a number of studies have demonstrated the use of WGS as an epidemiological tool for typing and controlling outbreaks of microbial pathogens. Success of these applications is hugely dependent on efficient generation of clean genetic material that is free from host DNA contamination for rapid preparation of sequencing libraries. The presence of large amounts of host DNA severely affects the efficiency of characterizing pathogens using WGS and is therefore a serious impediment to clinical and epidemiological sequencing for health care and public health applications. We have developed a simple enzymatic treatment method that takes advantage of the methylation of human DNA to selectively deplete host contamination from clinical samples prior to sequencing. Using malaria clinical samples with over 80% human host DNA contamination, we show that the enzymatic treatment enriches Plasmodium falciparum DNA up to ∼9-fold and generates high-quality, nonbiased sequence reads covering >98% of 86,158 catalogued typeable single-nucleotide polymorphism loci
Stellar Diameters and Temperatures. I. Main-Sequence A, F, and G Stars
We have executed a survey of nearby, main-sequence A-, F-, and G-type stars with the CHARA Array, successfully measuring the angular diameters of forty-four stars with an average precision of ~1.5%. We present new measures of the bolometric flux, which in turn leads to an empirical determination of the effective temperature for the stars observed. In addition, these CHARA-determined temperatures, radii, and luminosities are fit to Yonsei-Yale model isochrones to constrain the masses and ages of the stars. These results are compared to indirect estimates of these quantities obtained by collecting photometry of the stars and applying them to model atmospheres and evolutionary isochrones. We find that for most cases, the models overestimate the effective temperature by ~1.5%-4% when compared to our directly measured values. The overestimated temperatures and underestimated radii in these works appear to cause an additional offset in the star's surface gravity measurements, which consequently yield higher masses and younger ages, in particular for stars with masses greater than ~1.3 M_☉. Additionally, we compare our measurements to a large sample of eclipsing binary stars, and excellent agreement is seen within both data sets. Finally, we present temperature relations with respect to (B – V) and (V – K) colors as well as spectral type, showing that calibration of effective temperatures with errors ~1% is now possible from interferometric angular diameters of stars
Spectroscopy, MOST Photometry, and Interferometry of MWC 314: Is it an LBV or an interacting binary?
MWC 314 is a bright candidate luminous blue variable that resides in a fairly
close binary system, with an orbital period of 60.7530.003 d. We observed
MWC 314 with a combination of optical spectroscopy, broad-band ground- and
space-based photometry, as well as with long baseline, near-infrared
interferometry. We have revised the single-lined spectroscopic orbit and
explored the photometric variability. The orbital light curve displays two
minima each orbit that can be partially explained in terms of the tidal
distortion of the primary that occurs around the time of periastron. The
emission lines in the system are often double-peaked and stationary in their
kinematics, indicative of a circumbinary disc. We find that the stellar wind or
circumbinary disc is partially resolved in the K\prime-band with the longest
baselines of the CHARA Array. From this analysis, we provide a simple,
qualitative model in an attempt to explain the observations. From the
assumption of Roche Lobe overflow and tidal synchronisation at periastron, we
estimate the component masses to be M1 M and M2
M, which indicates a mass of the LBV that is extremely low. In addition
to the orbital modulation, we discovered two pulsational modes with the MOST
satellite. These modes are easily supported by a low-mass hydrogen-poor star,
but cannot be easily supported by a star with the parameters of an LBV. The
combination of these results provides evidence that the primary star was likely
never a normal LBV, but rather is the product of binary interactions. As such,
this system presents opportunities for studying mass-transfer and binary
evolution with many observational techniques.Comment: 26 pages, 7 figures, 5 tables, 2 appendices with 7 additional tables
and 2 additional figures. Accepted for publication in MNRA
Is type II diabetes mellitus (NIDDM) a surgical disease?
Since February 1, 1980, 515 morbidly obese patients have undergone
the Greenville gastric bypass (GGB) operation. Of these,
212 (41.2%) were euglycemic, 288 (55.9%) were either diabetic
or had glucose intolerance, and 15 (2.9%) were unable to complete
the evaluation. After the operation, only 30 (5.8%) patients remained
diabetic (and 20 of these improved), 457 (88.7%) became
and have remained euglycemic, and inadequate data prevented
classification of the other 28 (5.4%). The patients who failed to
return to normal glucose values were older and their diabetes
was of longer duration than those who did. The effect of the
GGB was not only limited to the correction of abnormal glucose
levels. The GGB also corrected the abnormal levels of fasting
insulin and glycosylated hemoglobin in a cohort of 52 consecutive
severely obese patients with non-insulin-dependent diabetes. The
GGB effectively controls weight. If morbid obesity is defined as
100 pounds over ideal body weight, 89% of the patients are no
longer "morbidly" obese within 2 years. In most patients, the
control of the weight has been well maintained during the 11
years of follow-up; most of the upward creep in weight of 20.8%
between 24 and 132 months was from the 49 (9.5%) patients
who had staple line breakdowns between the large and small
gastric pouches. Non-insulin-dependent diabetes, previously
considered a chronic unrelenting disease, can be controlled in
the severely obese by the gastric bypass. Whether the correction
of glucose metabolism affects the complications of diabetes is
unknown. Whether the gastric bypass should be considered for
patients with advanced non-insulin-dependent diabetes but who
are not severely obese deserves consideration. The GGB has an
unacceptably high rate of staple line failure. Accordingly, the
authors have recently changed their procedure to one that divides
the stomach rather than partitions it with staples. Originally published Annals of Surgery, Vol. 215, No. 6, June 199
Emergence of a unique group of necrotizing mycobacterial diseases.
Although most diseases due to pathogenic mycobacteria are caused by Mycobacterium tuberculosis, several other mycobacterial diseases-caused by M. ulcerans (Buruli ulcer), M. marinum, and M. haemophilum-have begun to emerge. We review the emergence of diseases caused by these three pathogens in the United States and around the world in the last decade. We examine the pathophysiologic similarities of the diseases (all three cause necrotizing skin lesions) and common reservoirs of infection (stagnant or slow-flowing water). Examination of the histologic and pathogenic characteristics of these mycobacteria suggests differences in the modes of transmission and pathogenesis, though no singular mechanism for either characteristic has been definitively described for any of these mycobacteria
Religious Factors and Hippocampal Atrophy in Late Life
Despite a growing interest in the ways spiritual beliefs and practices are reflected in brain activity, there have been relatively few studies using neuroimaging data to assess potential relationships between religious factors and structural neuroanatomy. This study examined prospective relationships between religious factors and hippocampal volume change using high-resolution MRI data of a sample of 268 older adults. Religious factors assessed included life-changing religious experiences, spiritual practices, and religious group membership. Hippocampal volumes were analyzed using the GRID program, which is based on a manual point-counting method and allows for semi-automated determination of region of interest volumes. Significantly greater hippocampal atrophy was observed for participants reporting a life-changing religious experience. Significantly greater hippocampal atrophy was also observed from baseline to final assessment among born-again Protestants, Catholics, and those with no religious affiliation, compared with Protestants not identifying as born-again. These associations were not explained by psychosocial or demographic factors, or baseline cerebral volume. Hippocampal volume has been linked to clinical outcomes, such as depression, dementia, and Alzheimer's Disease. The findings of this study indicate that hippocampal atrophy in late life may be uniquely influenced by certain types of religious factors
Convergent genetic and expression data implicate immunity in Alzheimer's disease
Background
Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis.
Methods
The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.
Results
ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05).
Conclusions
The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics
Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease
Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
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