74 research outputs found
Nondestructive SEM for surface and subsurface wafer imaging
The scanning electron microscope (SEM) is considered as a tool for both failure analysis as well as device characterization. A survey is made of various operational SEM modes and their applicability to image processing methods on semiconductor devices
Association Mining of Folk Music Genres and Toponyms
This paper demonstrates how association rule mining can be applied to discover relations between two ontologies of folk music: a genre and a region ontology. Genre– region associations have been widely studied in folk music research but have been neglected in music information retrieval. We present a method of association rule min- ing with constraints consisting of rule templates and rule evaluation measures to identify different, musicologically motivated, categories of genre–region associations. The method is applied to a corpus of 1902 Basque folk tunes, and several interesting rules and rule sets are discovere
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence
The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A–HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a “lock and key” interaction is typical of innate receptor–ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors
Quantitation of ortho-cresyl phosphate adducts to butyrylcholinesterase in human serum by immunomagnetic-UHPLC-MS/MS
Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids and gasoline. The neurotoxic effects of ToCP arise fromthe liver-activatedmetabolite 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP),which inhibits esterase enzymes including butyrylcholinesterase (BChE). Following BChE adduction, CBDP undergoes hydrolysis to formthe aged adduct ortho-cresyl phosphoserine (oCP-BChE), thus providing a biomarker of CBDP exposure. Previous studies have identified ToCP in aircraft cabin and cockpit air, but assessing human exposure has been hampered by the lack of a laboratory assay to confirm exposure. This work presents the development of an immunomagnetic- UHPLC-MS/MSmethod for the quantitation of unadducted BChE and the long-term CBDP biomarker, oCP-BChE, in human serum. Themethod has a reportable range from 2.0ng/ml to 150 ng/ml,which is consistent with the sensitivity ofmethods used to detect organophosphorus nerve agent protein adducts. The assay demonstrated high intraday and interday accuracy (≥85%) and precision (RSD≤ 15%) across the calibration range. The method was developed for future analyses of potential human exposure to CBDP. Analysis of human serum inhibited in vitro with CBDP demonstrated that the oCP-BChE adduct was stable for at least 72h at 4, 22 and 37 °C. Compared to a previously reported assay, this method requires 75% less sample volume, reduces analysis time by a factor of 20 and demonstrates a threefold improvement in sensitivity
Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study
Background Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute
neurological illness with high mortality among children occur annually in Muzaffarpur, the country’s largest litchi
cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness.
Methods In this hospital-based surveillance and nested age-matched case-control study, we did laboratory
investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were
children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or
altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals
for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood,
cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious
pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or
methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic
derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness
were expressed as matched odds ratios and odds ratios (unmatched analyses).
Findings Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral
hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration
of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched
odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness
onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis
on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal).
Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in
48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens
had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi
arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged
from 44·9 μg/g to 220·0 μg/g.
Interpretation Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both
hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising
litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected
illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations,
underscoring the importance of using systematic methods in other unexplained illness outbreaks
Acute mountain sickness.
Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days
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
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Classifying the evolutionary and ecological features of neoplasms
The consensus conference was supported by Wellcome Genome Campus Advanced Courses and Scientific Conferences. C.C.M. is supported in part by US NIH grants P01 CA91955, R01 CA149566, R01 CA170595, R01 CA185138 and R01 CA140657 as well as CDMRP Breast Cancer Research Program Award BC132057. M.J. is supported by NIH grant K99CA201606. K.S.A. is supported by NCI 5R21 CA196460. K. Polyak is supported by R35 CA197623, U01 CA195469, U54 CA193461, and the Breast Cancer Research Foundation. K.J.P. is supported by NIH grants CA143803, CA163124, CA093900 and CA143055. D.P. is supported by the European Research Council (ERC-617457- PHYLOCANCER), the Spanish Ministry of Economy and Competitiveness (BFU2015-63774-P) and the Education, Culture and University Development Department of the Galician Government. K.S.A. is supported in part by the Breast Cancer Research Foundation and NCI R21CA196460. C.S. is supported by the Royal Society, Cancer Research UK (FC001169), the UK Medical Research Council (FC001169), and the Wellcome Trust (FC001169), NovoNordisk Foundation (ID 16584), the Breast Cancer Research Foundation (BCRF), the European Research Council (THESEUS) and Marie Curie Network PloidyNet. T.A.G. is a Cancer Research UK fellow and a Wellcome Trust funded Investigator. E.S.H. is supported by R01 CA185138-01 and W81XWH-14-1-0473. M.Gerlinger is supported by Cancer Research UK and The Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre. M.Ge., M.Gr., Y.Y., and A.So. were also supported in part by the Wellcome Trust [105104/Z/14/Z]. J.D.S. holds the Edward B. Clark, MD Chair in Pediatric Research, and is supported by the Primary Children's Hospital (PCH) Pediatric Cancer Research Program, funded by the Intermountain Healthcare Foundation and the PCH Foundation. A.S. is supported by the Chris Rokos Fellowship in Evolution and Cancer. Y.Y. is a Cancer Research UK fellow and supported by The Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre. E.S.H. was supported in part by PCORI grants 1505–30497 and 1503–29572, NIH grants R01 CA185138, T32 CA093245, and U10 CA180857, CDMRP Breast Cancer Research Program Award BC132057, a CRUK Grand Challenge grant, and the Breast Cancer Research Foundation. A.R.A.A. was funded in part by NIH grant U01CA151924. A.R.A.A., R.G. and J.S.B. were funded in part by NIH grant U54CA193489
- …