A review of pseudo-labeling for computer vision

Deep neural models have achieved state of the art performance on a wide range of problems in computer science, especially in computer vision. However, deep neural networks often require large datasets of labeled samples to generalize effectively, and an important area of active research is semi-supervised learning, which attempts to instead utilize large quantities of (easily acquired) unlabeled samples. One family of methods in this space is pseudo-labeling, a class of algorithms that use model outputs to assign labels to unlabeled samples which are then used as labeled samples during training. Such assigned labels, called pseudo-labels, are most commonly associated with the field of semi-supervised learning. In this work we explore a broader interpretation of pseudo-labels within both self-supervised and unsupervised methods. By drawing the connection between these areas we identify new directions when advancements in one area would likely benefit others, such as curriculum learning and self-supervised regularization

Development and characterization of solid lipid-based formulations (sLBFs) of ritonavir utilizing a lipolysis and permeation assay

As a high number of active pharmaceutical ingredients (APIs) under development belong to BCS classes II and IV, the need for improving bioavailability is critical. A powerful approach is the use of lipid-based formulations (LBFs) that usually consist of a combination of liquid lipids, cosolvents, and surfactants. In this study, ritonavir loaded solid LBFs (sLBFs) were prepared using solid lipid excipients to investigate whether sLBFs are also capable of improving solubility and permeability. Additionally, the influence of polymeric precipitation inhibitors (PVP-VA and HPMC-AS) on lipolysis triggered supersaturation and precipitation was investigated. One step intestinal digestion and bicompartmental permeation studies using an artificial lecithin-in-dodecane (LiDo) membrane were performed for each formulation. All formulations presented significantly higher solubility (5 to >20-fold higher) during lipolysis and permeation studies compared to pure ritonavir. In the combined lipolysis-permeation studies, the formulated ritonavir concentration increased 15-fold in the donor compartment and the flux increased up to 71 % as compared to non-formulated ritonavir. The formulation with the highest surfactant concentration showed significantly higher ritonavir solubility compared to the formulation with the highest amount of lipids. However, the precipitation rates were comparable. The addition of precipitation inhibitors did not influence the lipolytic process and showed no significant benefit over the initial formulations with regards to precipitation. While all tested sLBFs increased the permeation rate, no statistically significant difference was noted between the formulations regardless of composition. To conclude, the different release profiles of the formulations were not correlated to the resulting flux through a permeation membrane, further supporting the importance of making use of combined lipolysis-permeation assays when exploring LBFs

Exploring the use of modified in vitro digestion assays for the evaluation of ritonavir loaded solid lipid-based formulations

Solid lipid-based formulations (sLBFs) have the potential to increase the oral bioavailability of drugs with poor solubility in water, while counteracting some of the disadvantages of liquid LBFs. The most common experimental set-up to study the performance of LBFs in vitro is the lipolysis assay, during which the LBFs are digested by lipases in an environment mimicking the human small intestine. However, this assay has failed in many cases to correctly predict the performance of LBFs in vivo, highlighting the need for new and improved in vitro assays to evaluate LBFs at the preclinical stage. In this study, the suitability of three different in vitro digestion assays for the evaluation of sLBFs was assessed; the classic one-step intestinal digestion assay, a two-step gastrointestinal digestion assay and a bicompartmental assay permitting the simultaneous monitoring of digestion and permeation of the active pharmaceutical ingredient (API) across an artificial membrane (Lecithin in Dodecane – LiDo). Three sLBFs (M1-M3) with varied composition and ritonavir as model drug were prepared and examined. When comparing the ability of these formulations to keep the drug solubilized in the aqueous phase, all three assays show that M1 performs better, while M3 presents poor performance. However, the classic in vitro intestinal digestion assay fails to provide a clear ranking of the three formulations, something that is more evident when using the two modified and more physiologically relevant assays. Also, the two modified assays provide additional information about the performance of the formulations including the performance in the gastric environment and intestinal flux of the drug. These modified in vitro digestion assays are valuable tools for the development and evaluation of sLBFs to make better informed decisions of which formulations to pursue for in vivo studies

Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Neuroscience 31 (2011): 9858-9868, doi:10.1523/JNEUROSCI.0560-11.2011.Aggregated filamentous forms of hyperphosphorylated tau (a microtubule-associated protein) represent pathological hallmarks of Alzheimer's disease (AD) and other tauopathies. While axonal transport dysfunction is thought to represent a primary pathogenic factor in AD and other neurodegenerative diseases, the direct molecular link between pathogenic forms of tau and deficits in axonal transport remain unclear. Recently, we demonstrated that filamentous, but not soluble, forms of wild-type tau inhibit anterograde, kinesin-based fast axonal transport (FAT) by activating axonal protein phosphatase 1 (PP1) and glycogen synthase kinase 3 (GSK3), independent of microtubule binding. Here, we demonstrate that amino acids 2–18 of tau, comprising a phosphatase-activating domain (PAD), are necessary and sufficient for activation of this pathway in axoplasms isolated from squid giant axons. Various pathogenic forms of tau displaying increased exposure of PAD inhibited anterograde FAT in squid axoplasm. Importantly, immunohistochemical studies using a novel PAD-specific monoclonal antibody in human postmortem tissue indicated that increased PAD exposure represents an early pathogenic event in AD that closely associates in time with AT8 immunoreactivity, an early marker of pathological tau. We propose a model of pathogenesis in which disease-associated changes in tau conformation lead to increased exposure of PAD, activation of PP1-GSK3, and inhibition of FAT. Results from these studies reveal a novel role for tau in modulating axonal phosphotransferases and provide a molecular basis for a toxic gain-of-function associated with pathogenic forms of tau.This work was supported by NIH Grants T32 AG020506-07 (N.M.K.); AG09466 (L.I.B.); and NS23868, NS23320, and NS41170 (S.T.B.); as well as 2007/2008 MBL Summer Research Fellowships and an ALS/CVS Therapy Alliance grant (G.M.)

Avian Host-Selection by Culex pipiens in Experimental Trials

Evidence from field studies suggests that Culex pipiens, the primary mosquito vector of West Nile virus (WNV) in the northeastern and north central United States, feeds preferentially on American robins (Turdus migratorius). To determine the contribution of innate preferences to observed preference patterns in the field, we conducted host preference trials with a known number of adult female C. pipiens in outdoor cages comparing the relative attractiveness of American robins with two common sympatric bird species, European starling, Sternus vulgaris and house sparrow, Passer domesticus. Host seeking C. pipiens were three times more likely to enter robin-baited traps when with the alternate host was a European starling (n = 4 trials; OR = 3.06; CI [1.42–6.46]) and almost twice more likely when the alternative was a house sparrow (n = 8 trials; OR = 1.80; CI = [1.22–2.90]). There was no difference in the probability of trap entry when two robins were offered (n = 8 trials). Logistic regression analysis determined that the age, sex and weight of the birds, the date of the trial, starting-time, temperature, humidity, wind-speed and age of the mosquitoes had no effect on the probability of a choosing a robin over an alternate bird. Findings indicate that preferential feeding by C. pipiens mosquitoes on certain avian hosts is likely to be inherent, and we discuss the implications innate host preferences may have on enzootic WNV transmission