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We describe a first reported case of shape-sensing robotic-assisted bronchoscopy using ION-intuitive platform done successfully under moderate sedation. A 76-year-old woman was found to have a right upper lobe mass measuring 3 × 2.9 cm. Diagnostic robotic navigational bronchoscopy was successfully performed under moderate sedation. Pathologic examination later revealed adenocarcinoma consistent with primary pulmonary malignancy. Conscious sedation allows the use of robotic bronchoscopy with minimal CT-to-body divergence and systems error. Robotic bronchoscopy under moderate sedation is feasible and seems to be safe and can be done without immediate complications.

Semiconductiong polymer nanoparticles (Pdots) have a wide range of applications in biomedical fields including biomolecular probes, tumor imaging, and therapy. However, there are few systematic studies on the biological effects and biocompatibility of Pdots in vitro and in vivo. The physicochemical properties of Pdots, such as surface modification, are very important in biomedical applications. Focusing on the central issue of the biological effects of Pdots, we systematically investigated the biological effects and biocompatibility of Pdots with different surface modifications and revealed the interactions between Pdots and organisms at the cellular and animal levels. The surfaces of Pdots were modified with different functional groups, including thiol, carboxyl, and amino groups, named Pdots@SH, Pdots@COOH, and Pdots@NH2, respectively. Extracellular studies showed that the modification of sulfhydryl, carboxyl, and amino groups had no significant effect on the physicochemical properties of Pdots, except that the amino modification affected the stability of Pdots to a certain extent. At the cellular level, Pdots@NH2 reduced cellular uptake capacity and increased cytotoxicity due to their instability in solution. At the in vivo level, the body circulation and metabolic clearance of Pdots@SH and Pdots@COOH were superior to those of Pdots@NH2. The four kinds of Pdots had no obvious effect on the blood indexes of mice and histopathological lesions in the main tissues and organs. This study provides important data for the biological effects and safety assessment of Pdots with different surface modifications, which pave the way for their potential biomedical applications.

Histone variants expand chromatin functions in eukaryote genomes. H2A.B genes are testis-expressed short histone H2A variants that arose in placental mammals. Their biological functions remain largely unknown. To investigate their function, we generated a knockout (KO) model that disrupts all 3 H2A.B genes in mice. We show that H2A.B KO males have globally altered chromatin structure in postmeiotic germ cells. Yet, they do not show impaired spermatogenesis or testis function. Instead, we find that H2A.B plays a crucial role postfertilization. Crosses between H2A.B KO males and females yield embryos with lower viability and reduced size. Using a series of genetic crosses that separate parental and zygotic contributions, we show that the H2A.B status of both the father and mother, but not of the zygote, affects embryonic viability and growth during gestation. We conclude that H2A.B is a novel parental-effect gene, establishing a role for short H2A histone variants in mammalian development. We posit that parental antagonism over embryonic growth drove the origin and ongoing diversification of short histone H2A variants in placental mammals.

Abstract Background Numerous empirical studies suggest that hosts and microbes exert reciprocal selective effects on their ecological partners. Nonetheless, we still lack an explicit framework to model the dynamics of both hosts and microbes under selection. In a previous study, we developed an agent-based forward-time computational framework to simulate the neutral evolution of host-associated microbial communities in a constant-sized, unstructured population of hosts. These neutral models allowed offspring to sample microbes randomly from parents and/or from the environment. Additionally, the environmental pool of available microbes was constituted by fixed and persistent microbial OTUs and by contributions from host individuals in the preceding generation. Methods In this paper, we extend our neutral models to allow selection to operate on both hosts and microbes. We do this by constructing a phenome for each microbial OTU consisting of a sample of traits that influence host and microbial fitnesses independently. Microbial traits can influence the fitness of hosts (“host selection”) and the fitness of microbes (“trait-mediated microbial selection”). Additionally, the fitness effects of traits on microbes can be modified by their hosts (“host-mediated microbial selection”). We simulate the effects of these three types of selection, individually or in combination, on microbiome diversities and the fitnesses of hosts and microbes over several thousand generations of hosts. Results We show that microbiome diversity is strongly influenced by selection acting on microbes. Selection acting on hosts only influences microbiome diversity when there is near-complete direct or indirect parental contribution to the microbiomes of offspring. Unsurprisingly, microbial fitness increases under microbial selection. Interestingly, when host selection operates, host fitness only increases under two conditions: (1) when there is a strong parental contribution to microbial communities or (2) in the absence of a strong parental contribution, when host-mediated selection acts on microbes concomitantly. Conclusions We present a computational framework that integrates different selective processes acting on the evolution of microbiomes. Our framework demonstrates that selection acting on microbes can have a strong effect on microbial diversities and fitnesses, whereas selection on hosts can have weaker outcomes.

Traditional approaches to differential privacy assume a fixed privacy requirement ε for a computation, and attempt to maximize the accuracy of the computation subject to the privacy constraint. As differential privacy is increasingly deployed in practical settings, it may often be that there is instead a fixed accuracy requirement for a given computation and the data analyst would like to maximize the privacy of the computation subject to the accuracy constraint. This raises the question of how to find and run a maximally private empirical risk minimizer subject to a given accuracy requirement. We propose a general “noise reduction” framework that can apply to a variety of private empirical risk minimization (ERM) algorithms, using them to “search” the space of privacy levels to find the empirically strongest one that meets the accuracy constraint, and incurring only logarithmic overhead in the number of privacy levels searched. The privacy analysis of our algorithm leads naturally to a version of differential privacy where the privacy parameters are dependent on the data, which we term ex-post privacy, and which is related to the recently introduced notion of privacy odometers. We also give an ex-post privacy analysis of the classical AboveThreshold privacy tool, modifying it to allow for queries chosen depending on the database. Finally, we apply our approach to two common objective functions, regularized linear and logistic regression, and empirically compare our noise reduction methods to (i) inverting the theoretical utility guarantees of standard private ERM algorithms and (ii) a stronger, empirical baseline based on binary search.

Enantioseparation is largely based on the formation of transitional complexes, the solvation species, the stationary phase configurations or the diastereomeric complexes formed by analytes and the chiral stationary phase. Temperature and the chemical nature and composition of the eluent play significant roles during that process. In this study; unique temperature-induced behaviors were observed during the enantioseparation of Koga tetraamines, also known as Koga bases, on polysaccharide chiral stationary phases, in which van’t Hoff plots were acquired over a temperature range of 10 °C to 40 °C with 5 °C increments. Koga bases were eluted by a mixture of methanol and 2-propanol with 0.03% triethylamine as a modifier. The van’t Hoff plots are linear in the case of eluent containing equal volumes of methanol and 2-propanol. Increasing 2-propanol concentration from 50% to 85% in volume led to non-linear van’t Hoff plots over the entire temperature range studied. Examination of the individual non-linear plots revealed two linear regions of 10 °C–20 °C and 20 °C–40 °C. Transition from one linear region to the other at 20 °C indicates alterations of chiral stationary phase conformation and/or enantioseparation mechanism as a result of temperature changes.

Apart from its role in axon guidance, netrin-1 is also known to be pro-angiogenic. The aim of this study is to determine whether adeno-associated viral (AAV) mediated overexpression of netrin-1 improves post-stroke neurovascular structure and recovery of function. AAV-Netrin-1 or AAV-LacZ of 1×1010 genome copies each was injected medial and posterior to ischemic lesion at one hour following reperfusion using the distal middle cerebral artery occlusion (MCAO) method. Quantitative RT-PCR revealed that the expression of netrin-1 transgene began as early as one day and increased dramatically about 3 weeks following vector injection. Western blot analysis and confocal microscopy suggested that both the endogenous and transduced netrin-1 were expressed in the neurons of the peri-infarct cortex after MCAO. AAV-mediated netrin-1 overexpression significantly increased vascular density in the peri-infarct cortex and promoted the migration of immature neurons into the peri-infarct white matter, but it did not significantly reduce infarct size. Netrin-1 overexpression also enhanced post-stroke locomotor activity, improved exploratory behavior, and reduced ischemia-induced motor asymmetry in forelimb usage. However, it had little effect on post-stroke spatial learning and memory. Our results suggest that AAV mediated netrin-1 overexpression improves peri-infarct vascular density and post stroke motor function.

There has been an explosion of research on host-associated microbial communities (i.e.,microbiomes). Much of this research has focused on surveys of microbial diversities across a variety of host species, including humans, with a view to understanding how these microbiomes are distributed across space and time, and how they correlate with host health, disease, phenotype, physiology and ecology. Fewer studies have focused on how these microbiomes may have evolved. In this paper, we develop an agent-based framework to study the dynamics of microbiome evolution. Our framework incorporates neutral models of how hosts acquire their microbiomes, and how the environmental microbial community that is available to the hosts is assembled. Most importantly, our framework also incorporates a Wright-Fisher genealogical model of hosts, so that the dynamics of microbiome evolution is studied on an evolutionary timescale. Our results indicate that the extent of parental contribution to microbial availability from one generation to the next significantly impacts the diversity of microbiomes: the greater the parental contribution, the less diverse the microbiomes. In contrast, even when there is only a very small contribution from a constant environmental pool, microbial communities can remain highly diverse. Finally, we show that our models may be used to construct hypotheses about the types of processes that operate to assemble microbiomes over evolutionary time.