507 research outputs found
Evolutionary Analysis Of ALPL Validates And Predicts Human Mutations Leading To Hypophosphatasia
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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
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
Splitting or lumping? A conservation dilemma exemplified by the critically endangered Dama Gazelle (Nanger dama)
Managers of threatened species often face the dilemma of whether to keep populations separate to conserve local adaptations and minimize the risk of outbreeding, or whether to manage populations jointly to reduce loss of genetic diversity and minimise inbreeding. In this study we examine genetic relatedness and diversity in three of the five last remaining wild populations of dama gazelle and a number of captive populations, using mtDNA control region and cytochrome b data. Despite the sampled populations belonging to the three putative subspecies, which are delineated according to phenotypes and geographical location, we find limited evidence for phylogeographical structure within the data and no genetic support for the putative subspecies. In the light of these data we discuss the relevance of inbreeding depression, outbreeding depression, adaptive variation, genetic drift, and phenotypic variation to the conservation of the dama gazelle and make some recommendations for its future conservation management. The genetic data suggest that the best conservation approach is to view the dama gazelle as a single species without subspecific divisions
Ka-to-l-band frequency down-conversion using a micro-photonic III-V-on-silicon mode-locked laser and mach-zehnder modulator
Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia: A Danish Population-Based Cohort Study
Objective: Diabetes mellitus contributes to excessive cardiovascular deaths and reduced life expectancy in schizophrenia. This population-based cohort study investigated the endogenous risk for diabetes in antipsychotic-naive schizophrenia and evaluated the risks added by starting antipsychotic treatment in people with schizophrenia. Method: The study followed all people born in Denmark onor after Jan. 1, 1977, until Jan. 1, 2013 (N=2,736,510). The Danish Psychiatric Central Research Register ascertained schizophrenia diagnoses. The Danish National Prescription Registry provided data on prescriptions of antipsychotics. Diabetes was ascertained fromthe Danish National Patient Register and Danish National Prescription Registry. The authors estimated the endogenous and antipsychotic-related risks for diabetes by using Cox proportional hazards regression models, while accounting for potential confounders. Results: Of the cohort members, 14,118 (0.52%) developed diabetes, and 8,945 (0.33%) developed schizophrenia during follow-up (49,582,279 person-years). The adjusted hazard ratio for diabetes was 3.07 (95% confidence interval [CI], 1.71-5.41) in antipsychotic-naive schizophrenia compared with the general population. The risk for diabetes after starting antipsychotic treatment was significantly higher (adjusted hazard ratio, 3.64; 95% CI, 1.95-6.82) than the risk in antipsychotic-naive schizophrenia, after adjustment for family history of diabetes and other potential confounders. First-line treatment with either first-generation antipsy-chotics (adjusted hazard ratio, 3.06; 95% CI, 1.32-7.05) or second-generation antipsychotics (adjusted hazard ratio, 3.44; 95% CI, 1.73-6.83) increased the risk for diabetes without a statistically significant difference. Appropriate sensitivity analyses limited to type 2 diabetes corroborated these results. Conclusions: Schizophrenia confers a high endogenous risk for diabetes, and the risk is further increased by both firstgeneration and second-generation antipsychotics. Early detection and effective treatment of diabetes should be an integral part of multidisciplinary management of schizophrenia regardless of antipsychotic drug exposure
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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