DeepNose: An Equivariant Convolutional Neural Network Predictive Of Human Olfactory Percepts.

The olfactory system employs responses of an ensemble of odorant receptors (ORs) to sense molecules and to generate olfactory percepts. Here we hypothesized that ORs can be viewed as 3D spatial filters that extract molecular features relevant to the olfactory system, similarly to the spatio-temporal filters found in other sensory modalities. To build these filters, we trained a convolutional neural network (CNN) to predict human olfactory percepts obtained from several semantic datasets.

Development of a fibrin-targeted theranostic for gastric cancer.

Patients with advanced gastric cancer (GCa) have limited treatment options, and alternative treatment approaches are necessary to improve their clinical outcomes. Because fibrin is abundant in gastric tumors but not in healthy tissues, we hypothesized that fibrin could be used as a high-concentration depot for a high-energy beta-emitting cytotoxic radiopharmaceutical delivered to tumor cells. We showed that fibrin is present in 64 to 75% of primary gastric tumors and 50 to 100% of metastatic gastric adenocarcinoma cores.

Encoding innate ability through a genomic bottleneck.

Animals are born with extensive innate behavioral capabilities, which arise from neural circuits encoded in the genome. However, the information capacity of the genome is orders of magnitude smaller than that needed to specify the connectivity of an arbitrary brain circuit, indicating that the rules encoding circuit formation must fit through a "genomic bottleneck" as they pass from one generation to the next. Here, we formulate the problem of innate behavioral capacity in the context of artificial neural networks in terms of lossy compression of the weight matrix.

Simultaneous Positron Emission Tomography and Molecular Magnetic Resonance Imaging of Cardiopulmonary Fibrosis in a Mouse Model of Left Ventricular Dysfunction.

Background: Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model.

Noninvasive Quantification of Radiation-Induced Lung Injury Using a Targeted Molecular Imaging Probe.

Purpose: Radiation-induced lung injury (RILI) is a progressive inflammatory process seen after irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management.

Detection of Pulmonary Fibrosis with a Collagen-Mimetic Peptide.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology that is characterized by excessive deposition and abnormal remodeling of collagen. IPF has a mean survival time of only 2-5 years from diagnosis, creating a need to detect IPF at an earlier stage when treatments might be more effective. We sought to develop a minimally invasive probe that could detect molecular changes in IPF-associated collagen.

Noninvasive Quantification of Radiation-Induced Lung Injury using a Targeted Molecular Imaging Probe.

Rationale: Radiation-induced lung injury (RILI) is a progressive inflammatory process commonly seen following irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management.

Optimization of an Allysine-Targeted PET Probe for Quantifying Fibrogenesis in a Mouse Model of Pulmonary Fibrosis.

Purpose: Idiopathic pulmonary fibrosis (IPF) is a destructive lung disease with a poor prognosis, an unpredictable clinical course, and inadequate therapies. There are currently no measures of disease activity to guide clinicians making treatment decisions. The aim of this study was to develop a PET probe to identify lung fibrogenesis using a pre-clinical model of pulmonary fibrosis, with potential for translation into clinical use to predict disease progression and inform treatment decisions.

Biodistribution, Dosimetry, and Pharmacokinetics of Ga-CBP8: A Type I Collagen-Targeted PET Probe.

The Ga-Collagen Binding Probe #8, Ga-CBP8, is a peptide-based, type I collagen-targeted probe developed for imaging of tissue fibrosis. The aim of this study was to determine the biodistribution, dosimetry, and pharmacokinetics of Ga-CBP8 in healthy human subjects. Nine healthy volunteers (5 male and 4 female) underwent whole-body Ga-CBP8 PET/MRI using a Biograph mMR scanner.

Spatiotemporal 3D image registration for mesoscale studies of brain development.

Comparison of brain samples representing different developmental stages often necessitates registering the samples to common coordinates. Although the available software tools are successful in registering 3D images of adult brains, registration of perinatal brains remains challenging due to rapid growth-dependent morphological changes and variations in developmental pace between animals. To address these challenges, we introduce CORGI (Customizable Object Registration for Groups of Images), an algorithm for the registration of perinatal brains.

Neural Networks With Motivation.

Animals rely on internal motivational states to make decisions. The role of motivational salience in decision making is in early stages of mathematical understanding. Here, we propose a reinforcement learning framework that relies on neural networks to learn optimal ongoing behavior for dynamically changing motivation values.

Molecular MR Contrast Agents.

Molecular magnetic resonance (MR) imaging utilizes molecular probes to provide added biochemical or cellular information to what can already be achieved with anatomical and functional MR imaging. This review provides an overview of molecular MR and focuses specifically on molecular MR contrast agents that provide contrast by shortening the T1 time. We describe the requirements for a successful molecular MR contrast agent and the challenges for clinical translation.

Revisiting dithiadiaza macrocyclic chelators for copper-64 PET imaging.

Synthesis and characterisation of a dithiadiaza chelator NSNS2A, as well as copper complexes thereof are reported in this paper. Solution structures of copper(i/ii) complexes were calculated using density functional theory (DFT) and validated by both NMR and EPR spectroscopy. DFT calculations revealed a switch in the orientation of tetragonal distortion upon protonation, which might be responsible for poor stability of the Cu(II)NSNS2A complex in aqueous media, whilst the same switch in tetragonal distortion was experimentally observed by changing the solvent.

Addressing prosthetic joint infections via gentamicin-eluting UHMWPE spacer.

Aims: We propose a state-of-the-art temporary spacer, consisting of a cobalt-chrome (CoCr) femoral component and a gentamicin-eluting ultra-high molecular weight polyethylene (UHMWPE) tibial insert, which can provide therapeutic delivery of gentamicin, while retaining excellent mechanical properties. The proposed implant is designed to replace conventional spacers made from bone cement.

Methods: Gentamicin-loaded UHMWPE was prepared using phase-separated compression moulding, and its drug elution kinetics, antibacterial, mechanical, and wear properties were compared with those of conventional gentamicin-loaded bone cement.

Click histochemistry for whole-mount staining of brain structures.

Labeling of the replicating DNA with synthetic thymidine analogs is commonly used for marking the dividing cells. However, until now this method has only been applied to histological sections. A growing number of current approaches for three-dimensional visualization of large tissue samples requires detection of dividing cells within whole organs.

Peroxidase Sensitive Amplifiable Probe for Molecular Magnetic Resonance Imaging of Pulmonary Inflammation.

An amplifiable magnetic resonance imaging (MRI) probe that combines the stability of the macrocyclic Gd-DOTAGA core with a peroxidase-reactive 5-hydroxytryptamide (5-HT) moiety is reported. The incubation of the complex under enzymatic oxidative conditions led to a 1.7-fold increase in at 1.

Network cloning using DNA barcodes.

The connections between neurons determine the computations performed by both artificial and biological neural networks. Recently, we have proposed SYNSeq, a method for converting the connectivity of a biological network into a form that can exploit the tremendous efficiencies of high-throughput DNA sequencing. In SYNSeq, each neuron is tagged with a random sequence of DNA-a "barcode"-and synapses are represented as barcode pairs.

Suppressed neurogenesis without cognitive deficits: effects of fast neutron irradiation in mice.

This study assessed the effects of combined low-dose neutron and γ-ray irradiation on hippocampal neurogenesis and hippocampal-dependent memory. Neural progenitor cell division and survival were evaluated in brain sections and whole hippocampal preparations following head irradiation at a dose of 0.34 Gy for neutron radiation and 0.

A near-IR luminescent ratiometric ytterbium pH probe.

The hypersensitive 2F5/2 to 2F7/2 transition of Yb3+ can be used to monitor perturbations of the coordination sphere in ytterbium(iii) complexes. An envelope of Stark components gives rise to a relatively broad and asymmetric emission band, whilst changes in their relative intensity and energy enable a ratiometric response. We report a new ytterbium complex with a sulphonamide arm that binds reversibly to Yb3+ as a function of pH, giving rise to significant pH dependent changes in the Yb emission spectrum.

Selective signalling of glyphosate in water using europium luminescence.

A series of four emissive europium complexes has been evaluated for the binding of glyphosate in various aqueous media, including river water and grain extracts. Binding selectivity toward inorganic phosphate and bicarbonate was enhanced by measuring samples at pH 5.9, above the pKa of glyphosate itself.

Chiral probes for α-AGP reporting by species-specific induced circularly polarised luminescence.

Luminescence spectroscopy has been used to monitor the selective and reversible binding of pH sensitive, macrocyclic lanthanide complexes, , to the serum protein α-AGP, whose concentration can vary significantly in response to inflammatory processes. On binding α-AGP, a very strong induced circularly-polarised europium luminescence signal was observed that was of opposite sign for human and bovine variants of α-AGP - reflecting the differences in the chiral environment of their drug-binding pockets. A mixture of and complexes allowed the ratiometric monitoring of α-AGP levels in serum.

Monitoring of the ADP/ATP Ratio by Induced Circularly Polarised Europium Luminescence.

A series of three europium complexes bearing picolyl amine moieties was found to possess differing binding affinities towards Zn and three nucleotides: AMP, ADP, and ATP. A large increase in the total emission intensity was observed upon binding Zn , followed by signal amplification upon the addition of nucleotides. The resulting adducts possessed strong induced circularly polarised emission, with ADP and ATP signals of opposite sign.

DALMATIAN: An Algorithm for Automatic Cell Detection and Counting in 3D.

Current 3D imaging methods, including optical projection tomography, light-sheet microscopy, block-face imaging, and serial two photon tomography enable visualization of large samples of biological tissue. Large volumes of data obtained at high resolution require development of automatic image processing techniques, such as algorithms for automatic cell detection or, more generally, point-like object detection. Current approaches to automated cell detection suffer from difficulties originating from detection of particular cell types, cell populations of different brightness, non-uniformly stained, and overlapping cells.