633 research outputs found
Everolimus dosing recommendations for tuberous sclerosis complex–associated refractory seizures
ObjectiveThe present analysis examined the exposure-response relationship by means of the predose everolimus concentration (C-min) and the seizure response in patients with tuberous sclerosis complex-associated seizures in the EXIST-3 study. Recommendations have been made for the target C-min range of everolimus for therapeutic drug monitoring (TDM) and the doses necessary to achieve this target C-min
Hysteretic Magnetotransport in SmB6 at Low Magnetic Fields
Utilizing Corbino disc structures, we have examined the magnetic field
response of resistivity for the surface states of SmB6 on different crystalline
surfaces at low temperatures. Our results reveal a hysteretic behavior whose
magnitude depends on the magnetic field sweep rate and temperature. Although
this feature becomes smaller when the field sweep is slower, a complete
elimination or saturation is not observed in our slowest sweep-rate
measurements, which is much slower than a typical magnetotransport trace. These
observations cannot be explained by quantum interference corrections such as
weak anti-localization. Instead, they are consistent with behaviors of glassy
surface magnetic ordering, whose magnetic origin is most likely from samarium
oxide (Sm2O3) forming on the surface during exposure to ambient conditions
Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity.
Breast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we use single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produces one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides insights into the cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer
An infrared integrated optic astronomical beam combiner for stellar interferometry at 3-4 microns
Integrated-optic, astronomical, two-beam and three-beam, interferometric
combiners have been designed and fabricated for operation in the L band (3 - 4
microns) for the first time. The devices have been realized in
titanium-indiffused, x-cut lithium niobate substrates, and on-chip
electro-optic fringe scanning has been demonstrated. White light fringes were
produced in the laboratory using the two-beam combiner integrated with an
on-chip Y-splitter.Comment: This paper was published in Optics Express and is made available as
an electronic reprint with the permission of OSA. The paper can be found at
the following URL on the OSA website: http://www.opticsinfobase.org/oe.
Systematic or multiple reproduction or distribution to multiple locations via
electronic or other means is prohibited and is subject to penalties under la
Size-dependent melting: Numerical calculations of the phonon spectrum
In order to clarify the relationship between the phonon spectra of
nanoparticles and their melting temperature, we studied in detail the
size-dependent low energy vibration modes. A minimum model with atoms on a
lattice and harmonic potentials for neighboring atoms is used to reveal a
general behavior. By calculating the phonon spectra for a series of
nanoparticles of two lattice types in different sizes, we found that density of
low energy modes increases as the size of nanoparticles decreases, and this
density increasing causes decreasing of melting temperature. Size-dependent
behavior of the phonon spectra accounts for typical properties of
surface-premelting and irregular melting temperature on fine scales. These
results show that our minimum model captures main physics of nanoparticles.
Therefore, more physical characteristics for nanoparticles of certain types can
be given by phonons and microscopic potential models.Comment: 5 pages, 5 figure
Genotype, haplotype and copy-number variation in worldwide human populations
Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups(1-3). Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms ( SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected-including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas-the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62552/1/nature06742.pd
Characterisation of age and polarity at onset in bipolar disorder
Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses
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