592 research outputs found
Numerical evidences of spin-1/2 chain approaching spin-1 chain
In this article, we study the one dimensional Heisenberg spin-1/2 alternating
bond chain in which the nearest neighbor exchange couplings are ferromagnetic
(FM) and antiferromagnetic (AF) alternatively. By using exact diagonalization
and density matrix renormalization groups (DMRG) method, we discuss how the
system approaches to the AF uniform spin-1 chain under certain condition. When
the ratio of AF to FM coupling strength}
\textit{is very small, the physical quantities of the alternating bond chain
such as the spin-spin correlation, the string correlation function and the spin
density coincide with that of the AF uniform spin-1 chain. The edge state
problem is discussed in the present model with small}\textit{limit. In
addition, the Haldane gap of the AF uniform spin-1 chain is 4-times of the gap
of the system considered.Comment: 9pages,8page
Lifetime Measurements in 120Xe
Lifetimes for the lowest three transitions in the nucleus Xe have
been measured using the Recoil Distance Technique. Our data indicate that the
lifetime for the transition is more than a factor of
two lower than the previously adopted value and is in keeping with more recent
measurements performed on this nucleus. The theoretical implications of this
discrepancy and the possible reason for the erroneous earlier results are
discussed. All measured lifetimes in Xe, as well as the systematics of
the lifetimes of the 2 states in Xe isotopes, are compared with
predictions of various models. The available data are best described by the
Fermion Dynamic Symmetry Model (FDSM).Comment: 9 pages, RevTeX, 3 figures with Postscript file available on request
at [email protected], [email protected]. Submitted to Phys.
Rev.
Switchable genome editing via genetic code expansion
Multiple applications of genome editing by CRISPR-Cas9 necessitate stringent regulation and Cas9 variants have accordingly been generated whose activity responds to small ligands, temperature or light. However, these approaches are often impracticable, for example in clinical therapeutic genome editing in situ or gene drives in which environmentally-compatible control is paramount. With this in mind, we have developed heritable Cas9-mediated mammalian genome editing that is acutely controlled by the cheap lysine derivative, Lys(Boc) (BOC). Genetic code expansion permitted non-physiological BOC incorporation such that Cas9 (Cas9BOC) was expressed in a full-length, active form in cultured somatic cells only after BOC exposure. Stringently BOC-dependent, heritable editing of transgenic and native genomic loci occurred when Cas9BOC was expressed at the onset of mouse embryonic development from cRNA or Cas9BOC transgenic females. The tightly controlled Cas9 editing system reported here promises to have broad applications and is a first step towards purposed, spatiotemporal gene drive regulation over large geographical ranges
ΔFosB Regulates Gene Expression and Cognitive Dysfunction in a Mouse Model of Alzheimer\u27s Disease.
Alzheimer\u27s disease (AD) is characterized by cognitive decline and 5- to 10-fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show that spontaneous seizures increase expression of ΔFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. ΔFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation. Acute histone deacetylase (HDAC) inhibition or inhibition of ΔFosB activity restored c-Fos induction and improved cognition in AD mice. Administration of seizure-inducing agents to nontransgenic mice also resulted in ΔFosB-mediated suppression of c-Fos, suggesting that this mechanism is not confined to AD mice. These results explain observations that c-Fos expression increases after acute neuronal activity but decreases with chronic activity. Moreover, these results indicate a general mechanism by which seizures contribute to persistent cognitive deficits, even during seizure-free periods
Hermitian quark mass matrices with four texture zeros
We provide a complete and systematic analysis of hermitian, hierarchical
quark mass matrices with four texture zeros. Using triangular mass matrices,
each pattern of texture zeros is readily shown to lead to a definite relation
between the CKM parameters and the quark masses. Nineteen pairs are found to be
consistent with present data, and one other is marginally acceptable. In
particular, no parallel structure between the up and down mass matrices is
found to be favorable with data.Comment: 18 pages, no figure, references [8] and [10] adde
Shear instabilities of freely standing thermotropic smectic-A films
In this Letter we discuss theoretically the instabilities of thermotropic
freely standing smectic-A films under shear flow\cite{re:wu}. We show that, in
Couette geometry, the centrifugal force pushes the liquid crystal toward the
outer boundary and induces smectic layer dilation close to the outer boundary.
Under strong shear, this effect induces a layer buckling instability. The
critical shear rate is proportional to , where is the thickness
of the film.Comment: 12 pages, 2 figure
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Evaluation of Machine-Learning Algorithms for Predicting Opioid Overdose Risk Among Medicare Beneficiaries With Opioid Prescriptions
IMPORTANCE Current approaches to identifying individuals at high risk for opioid overdose target many patients who are not truly at high risk. OBJECTIVE To develop and validate a machine-learning algorithm to predict opioid overdose risk among Medicare beneficiaries with at least 1 opioid prescription. DESIGN, SETTING, AND PARTICIPANTS A prognostic study was conducted between September 1, 2017, and December 31, 2018. Participants (n = 560 057) included fee-for-service Medicare beneficiaries without cancer who filled 1 or more opioid prescriptions from January 1, 2011, to December 31, 2015. Beneficiaries were randomly and equally divided into training, testing, and validation samples. EXPOSURES Potential predictors (n = 268), including sociodemographics, health status, patterns of opioid use, and practitioner-level and regional-level factors, were measured in 3-month windows, starting 3 months before initiating opioids until loss of follow-up or the end of observation. MAIN OUTCOMES AND MEASURES Opioid overdose episodes from inpatient and emergency department claims were identified. Multivariate logistic regression (MLR), least absolute shrinkage and selection operator-type regression (LASSO), random forest (RF), gradient boosting machine (GBM), and deep neural network (DNN) were applied to predict overdose risk in the subsequent 3 months after initiation of treatment with prescription opioids. Prediction performance was assessed using the C statistic and other metrics (eg, sensitivity, specificity, and number needed to evaluate [NNE] to identify one overdose). The Youden index was used to identify the optimized threshold of predicted score that balanced sensitivity and specificity. RESULTS Beneficiaries in the training (n = 186 686), testing (n = 186 685), and validation (n = 186 686) samples had similar characteristics (mean [SD] age of 68.0 [14.5] years, and approximately 63% were female, 82% were white, 35% had disabilities, 41% were dual eligible, and 0.60% had at least 1 overdose episode). In the validation sample, the DNN (C statistic = 0.91; 95% CI, 0.88-0.93) and GBM (C statistic = 0.90; 95% CI, 0.87-0.94) algorithms outperformed the LASSO (C statistic = 0.84; 95% CI, 0.80-0.89), RF (C statistic = 0.80; 95% CI, 0.75-0.84), and MLR (C statistic = 0.75; 95% CI, 0.69-0.80) methods for predicting opioid overdose. At the optimized sensitivity and specificity, DNN had a sensitivity of 92.3%, specificity of 75.7%, NNE of 542, positive predictive value of 0.18%, and negative predictive value of 99.9%. The DNN classified patients into low-risk (76.2%[142 180] of the cohort), medium-risk (18.6%[34 579] of the cohort), and high-risk (5.2%[9747] of the cohort) subgroups, with only 1 in 10 000 in the low-risk subgroup having an overdose episode. More than 90% of overdose episodes occurred in the high-risk and medium-risk subgroups, although positive predictive values were low, given the rare overdose outcome. CONCLUSIONS AND RELEVANCE Machine-learning algorithms appear to perform well for risk prediction and stratification of opioid overdose, especially in identifying low-risk subgroups that have minimal risk of overdose.NIH/National Institute on Drug Abuse [R01DA044985]; Pharmaceutical Research and Manufacturers of America Foundation Research Starter AwardOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Deep learning-based survival prediction for multiple cancer types using histopathology images
Prognostic information at diagnosis has important implications for cancer
treatment and monitoring. Although cancer staging, histopathological
assessment, molecular features, and clinical variables can provide useful
prognostic insights, improving risk stratification remains an active research
area. We developed a deep learning system (DLS) to predict disease specific
survival across 10 cancer types from The Cancer Genome Atlas (TCGA). We used a
weakly-supervised approach without pixel-level annotations, and tested three
different survival loss functions. The DLS was developed using 9,086 slides
from 3,664 cases and evaluated using 3,009 slides from 1,216 cases. In
multivariable Cox regression analysis of the combined cohort including all 10
cancers, the DLS was significantly associated with disease specific survival
(hazard ratio of 1.58, 95% CI 1.28-1.70, p<0.0001) after adjusting for cancer
type, stage, age, and sex. In a per-cancer adjusted subanalysis, the DLS
remained a significant predictor of survival in 5 of 10 cancer types. Compared
to a baseline model including stage, age, and sex, the c-index of the model
demonstrated an absolute 3.7% improvement (95% CI 1.0-6.5) in the combined
cohort. Additionally, our models stratified patients within individual cancer
stages, particularly stage II (p=0.025) and stage III (p<0.001). By developing
and evaluating prognostic models across multiple cancer types, this work
represents one of the most comprehensive studies exploring the direct
prediction of clinical outcomes using deep learning and histopathology images.
Our analysis demonstrates the potential for this approach to provide prognostic
information in multiple cancer types, and even within specific pathologic
stages. However, given the relatively small number of clinical events, we
observed wide confidence intervals, suggesting that future work will benefit
from larger datasets
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