3,260 research outputs found

    On parameter estimation with the Wasserstein distance

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    Statistical inference can be performed by minimizing, over the parameter space, the Wasserstein distance between model distributions and the empirical distribution of the data. We study asymptotic properties of such minimum Wasserstein distance estimators, complementing results derived by Bassetti, Bodini and Regazzini in 2006. In particular, our results cover the misspecified setting, in which the data-generating process is not assumed to be part of the family of distributions described by the model. Our results are motivated by recent applications of minimum Wasserstein estimators to complex generative models. We discuss some difficulties arising in the approximation of these estimators and illustrate their behavior in several numerical experiments. Two of our examples are taken from the literature on approximate Bayesian computation and have likelihood functions that are not analytically tractable. Two other examples involve misspecified models.Comment: 29 pages (+18 pages of appendices), 6 figures. To appear in Information and Inference: A Journal of the IMA. A previous version of this paper contained work on approximate Bayesian computation with the Wasserstein distance, which can now be found at arxiv:1905.0374

    Linear response functions for a vibrational configuration interaction state

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    Linear response functions are implemented for a vibrational configuration interaction state allowing accurate analytical calculations of pure vibrational contributions to dynamical polarizabilities. Sample calculations are presented for the pure vibrational contributions to the polarizabilities of water and formaldehyde. We discuss the convergence of the results with respect to various details of the vibrational wave function description as well as the potential and property surfaces. We also analyze the frequency dependence of the linear response function and the effect of accounting phenomenologically for the finite lifetime of the excited vibrational states. Finally, we compare the analytical response approach to a sum-over-states approac

    Rapid and Deep Remission Induced by Blinatumomab for CD19-Positive Chronic Myeloid Leukemia in Lymphoid Blast Phase

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    In summary, we show rapid and deep remission induced by blinatumomab in CD19(+) blast phase CML. Clinicians may consider the use of bispecific T-cell engager therapy as a bridge to transplant. Additional studies are needed before expanding the US Food and Drug Administration indication of blinatumomab to include lymphoid blast phase CML

    Leucine Rich α-2 Glycoprotein: A Novel Neutrophil Granule Protein and Modulator of Myelopoiesis

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    Leucine-rich α2 glycoprotein (LRG1), a serum protein produced by hepatocytes, has been implicated in angiogenesis and tumor promotion. Our laboratory previously reported the expression of LRG1 in murine myeloid cell lines undergoing neutrophilic granulocyte differentiation. However, the presence of LRG1 in primary human neutrophils and a role for LRG1 in regulation of hematopoiesis have not been previously described. Here we show that LRG1 is packaged into the granule compartment of human neutrophils and secreted upon neutrophil activation to modulate the microenvironment. Using immunofluorescence microscopy and direct biochemical measurements, we demonstrate that LRG1 is present in the peroxidase-negative granules of human neutrophils. Exocytosis assays indicate that LRG1 is differentially glycosylated in neutrophils, and co-released with the secondary granule protein lactoferrin. Like LRG1 purified from human serum, LRG1 secreted from activated neutrophils also binds cytochrome c. We also show that LRG1 antagonizes the inhibitory effects of TGFβ1 on colony growth of human CD34+ cells and myeloid progenitors. Collectively, these data invoke an additional role for neutrophils in innate immunity that has not previously been reported, and suggest a novel mechanism whereby neutrophils may modulate the microenvironment via extracellular release of LRG1

    Data-driven honeybee antennal lobe model suggests how stimulus-onset asynchrony can aid odour segregation

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    Insects have a remarkable ability to identify and track odour sources in multi-odour backgrounds. Recent behavioural experiments show that this ability relies on detecting millisecond stimulus asynchronies between odourants that originate from different sources. Honeybees, Apis mellifera , are able to distinguish mixtures where both odourants arrive at the same time (synchronous mixtures) from those where odourant onsets are staggered (asynchronous mixtures) down to an onset delay of only 6 ms. In this paper we explore this surprising ability in a model of the insects' primary olfactory brain area, the antennal lobe. We hypothesize that a winner-take-all inhibitory network of local neurons in the antennal lobe has a symmetry-breaking effect, such that the response pattern in projection neurons to an asynchronous mixture is different from the response pattern to the corresponding synchronous mixture for an extended period of time beyond the initial odourant onset where the two mixture conditions actually differ. The prolonged difference between response patterns to synchronous and asynchronous mixtures could facilitate odour segregation in downstream circuits of the olfactory pathway. We present a detailed data-driven model of the bee antennal lobe that reproduces a large data set of experimentally observed physiological odour responses, successfully implements the hypothesised symmetry-breaking mechanism and so demonstrates that this mechanism is consistent with our current knowledge of the olfactory circuits in the bee brain

    Comprehensive Review of Acute Pancreatitis Pain Syndrome

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    Pancreatitis is a condition that causes inflammation in the pancreas, an organ located behind the stomach. This condition often presents as neuropathic, inflammatory, and/or visceral pain. Acute pancreatitis is typically characterized by sudden and severe abdominal pain, often in the upper right part of the abdomen. The pain from pancreatitis can be caused by different mechanisms, such as abnormal activation of pancreatic zymogens or NF-κB mediated inflammation in the pancreas. The treatment of pancreatitis depends on its type, severity, and underlying cause. Hospitalization and medications are typically necessary, while in others, surgery may be required. Proper management of pancreatitis is essential, as it can help reduce the risk of complications and improve the patient’s quality of life. The literature on pancreatitis pain management evaluates systematic approaches and the effectiveness of various treatments, such as lidocaine, opioid agonists, ketamine, magnesium, endoscopic methods, spinal cord stimulation, and other novel treatments present opportunities for exploration in pancreatitis pain management

    Tinkering Evolution of Post-Transcriptional RNA Regulons: Puf3p in Fungi as an Example

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    Genome-wide studies of post-transcriptional mRNA regulation in model organisms indicate a “post-transcriptional RNA regulon” model, in which a set of functionally related genes is regulated by mRNA–binding RNAs or proteins. One well-studied post-transcriptional regulon by Puf3p functions in mitochondrial biogenesis in budding yeast. The evolution of the Puf3p regulon remains unclear because previous studies have shown functional divergence of Puf3p regulon targets among yeast, fruit fly, and humans. By analyzing evolutionary patterns of Puf3p and its targeted genes in forty-two sequenced fungi, we demonstrated that, although the Puf3p regulon is conserved among all of the studied fungi, the dedicated regulation of mitochondrial biogenesis by Puf3p emerged only in the Saccharomycotina clade. Moreover, the evolution of the Puf3p regulon was coupled with evolution of codon usage bias in down-regulating expression of genes that function in mitochondria in yeast species after genome duplication. Our results provide a scenario for how evolution like a tinker exploits pre-existing materials of a conserved post-transcriptional regulon to regulate gene expression for novel functional roles
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