443 research outputs found
Hybrid Models for Learning to Branch
A recent Graph Neural Network (GNN) approach for learning to branch has been
shown to successfully reduce the running time of branch-and-bound algorithms
for Mixed Integer Linear Programming (MILP). While the GNN relies on a GPU for
inference, MILP solvers are purely CPU-based. This severely limits its
application as many practitioners may not have access to high-end GPUs. In this
work, we ask two key questions. First, in a more realistic setting where only a
CPU is available, is the GNN model still competitive? Second, can we devise an
alternate computationally inexpensive model that retains the predictive power
of the GNN architecture? We answer the first question in the negative, and
address the second question by proposing a new hybrid architecture for
efficient branching on CPU machines. The proposed architecture combines the
expressive power of GNNs with computationally inexpensive multi-linear
perceptrons (MLP) for branching. We evaluate our methods on four classes of
MILP problems, and show that they lead to up to 26% reduction in solver running
time compared to state-of-the-art methods without a GPU, while extrapolating to
harder problems than it was trained on.Comment: Preprint. Under revie
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Clozapine use in childhood and adolescent schizophrenia: A nationwide population-based study
Early onset schizophrenia (EOS) begins in childhood or adolescence. EOS is associated with poor treatment response and may benefit from timely use of clozapine. This study aimed to identify the predictors of clozapine use in EOS and characterize the clinical profile and outcome of clozapine-treated youths with schizophrenia. We conducted a nationwide population-based study using linked data from Danish medical registries. We examined all incident cases of EOS (i.e., cases diagnosed prior to their 18th birthday) between December 31st 1994 and December 31st 2006 and characterized their demographic, clinical and treatment profiles. We then used multivariable cox proportional hazard models to identify predictors of clozapine treatment in this patient population. We identified 662 EOS cases (1.9% of all schizophrenia cases), of whom 108 (17.6%) had commenced clozapine by December 31st 2008. Patients had on average 3 antipsychotic trials prior to clozapine initiation. The mean interval between first antipsychotic treatment and clozapine initiation was 3.2 (2.9) years. Older age at diagnosis of schizophrenia [HR=1.2, 95% CI (1.05-1.4), p=0.01], family history of schizophrenia [HR=2.1, 95% CI (1.1-3.04), p=0.02] and attempted suicide [HR=1.8, 95% CI (1.1-3.04), p=0.02] emerged as significant predictors of clozapine use. The majority of patients (n=96, 88.8%) prescribed clozapine appeared to have a favorable clinical response as indicated by continued prescription redemption and improved occupational outcomes. Our findings support current recommendations for the timely use of clozapine in EOS
Modulation of BACE1 Activity by Chemically Modified Aptamers
A modified DNA aptamer that binds BACE1, a therapeutic target involved in Alzheimer's disease has been developed. This ssXNA not only tightly binds to BACE1 but also inhibits its protease activity in vitro in the same range as a previously described unmodified aptamer. We report the in vitro selection of functional oligonucleotides incorporating two nucleobase modifications: 5‐chlorouracil and 7‐deazaadenine. The nucleoside analogue 5‐chloro‐2′‐deoxyuridine has already been explored as a replacement for thymidine in a chemically modified genome of a bacterium. Thus, 5‐chlorouracil modification is a good candidate to support genetic transfer in vivo as well as functional activity
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Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora
Background
The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years.
Results
Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology.
Conclusions
Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record
Florida Straits density structure and transport over the last 8000 years
Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 24 (2009): PA3209, doi:10.1029/2008PA001717.The density structure across the Florida Straits is reconstructed for the last 8000 years from oxygen isotope measurements on foraminifera in sediment cores. The oxygen isotope measurements suggest that the density contrast across the Florida Current increased over this time period. The magnitude of this change corresponds to an increase in the geostrophic transport referenced to 800 m water depth of 4 sverdrups (Sv) over the last 8000 years. The spatial and seasonal distribution of incoming solar radiation due to changes in the Earth's orbit has caused systematic changes in the atmospheric circulation, including a southward migration of the Intertropical Convergence Zone over the last 8000 years. These changes in atmospheric circulation and the associated wind-driven currents of the upper ocean could readily account for a 4 Sv increase in the strength of the Florida Current. We see no evidence in our data for dramatic changes in the strength of the Atlantic Meridional Overturning Circulation over this time period.This work was supported by NSF grants
OCE-9984989/OCE-0428803 and OCE-0096472 to J.L.-S. and NSF grants
OCE-0096469 to W.B.C
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