The Magnitude of Lift Forces Acting on Drops and Bubbles in Liquids Flowing Inside Microchannels

Hydrodynamic lift forces offer a convenient way to manipulate particles in microfluidic applications, but there is little quantitative information on how non-inertial lift mechanisms act and compete with each other in the confined space of microfluidic channels. This paper reports measurements of lift forces on nearly spherical drops and bubbles, with diameters from one quarter to one half of the width of the channel, flowing in microfluidic channels, under flow conditions characterized by particle capillary numbers CaP = 0.0003–0.3 and particle Reynolds numbers ReP = 0.0001–0.1. For CaP < 0.01 and ReP < 0.01 the measured lift forces were much larger than predictions of deformation-induced and inertial lift forces found in the literature, probably due to physicochemical hydrodynamic effects at the interface of drops and bubbles, such as the presence of surfactants. The measured forces could be fit with good accuracy using an empirical formula given herein. The empirical formula describes the power-law dependence of the lift force on hydrodynamic parameters (velocity and viscosity of the carrier phase; sizes of channel and drop or bubble), and includes a numerical lift coefficient that depends on the fluids used. The empirical formula using an average lift coefficient of [similar]500 predicted, within one order of magnitude, all lift force measurements in channels with cross-sectional dimensions below 1 mm.Chemistry and Chemical Biolog

Methods & proposal for metadata guiding principles for scholarly communications

This article describes an international community-based effort to create metadata guiding principles for adopting and using richer metadata and advancing its application in scholarly communications. These principles can facilitate the dissemination, discoverability and use/reuse of many types of research and scholarly outputs. While much work remains to be done, these principles serve as a starting point for the evolution of processes that span communities including publishers, researchers, scholars, authors and other creators, librarians, curators, custodians, and consumers of scholarly works. These aspirational Metadata 2020 Principles are designed to encompass the needs of our entire community while ensuring thoughtful, purposeful, and reusable metadata resources. They provide a framework for all of us to be good metadata citizens. They also provide a foundation for considering related work from Metadata 2020 and must be interpreted within the legal and practical context in which we operate. They are intended to guide the broadest possible cross-section of our community in improving research communications, publishing, and discoverability

PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication

DNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (PrimPol; CCDC111), an archaeal-eukaryotic primase (AEP) in eukaryotic cells, is involved in chromosomal DNA replication. PrimPol is required for replication fork progression on ultraviolet (UV) lightdamaged DNA templates, possibly mediated by its ability to catalyze translesion synthesis (TLS) of these lesions. This PrimPol UV lesion bypass pathway is not epistatic with the Pol h-dependent pathway and, as a consequence, protects xeroderma pigmentosum variant (XP-V) patient cells from UV-induced cytotoxicity. In addition, we establish that PrimPol is also required for efficient replication fork progression during an unperturbed S phase. These and other findings indicate that PrimPol is an important player in replication fork progression in eukaryotic cells

Annexin A8 identifies a subpopulation of transiently quiescent c-kit positive luminal progenitor cells of the ductal mammary epithelium

We have previously shown that Annexin A8 (ANXA8) is strongly associated with the basal-like subgroup of breast cancers, including BRCA1-associated breast cancers, and poor prognosis; while in the mouse mammary gland AnxA8 mRNA is expressed in low-proliferative isolated pubertal mouse mammary ductal epithelium and after enforced involution, but not in isolated highly proliferative terminal end buds (TEB) or during pregnancy. To better understand ANXA8’s association with this breast cancer subgroup we established ANXA8’s cellular distribution in the mammary gland and ANXA8’s effect on cell proliferation. We show that ANXA8 expression in the mouse mammary gland was strong during pre-puberty before the expansion of the rudimentary ductal network and was limited to a distinct subpopulation of ductal luminal epithelial cells but was not detected in TEB or in alveoli during pregnancy. Similarly, during late involution its expression was found in the surviving ductal epithelium, but not in the apoptotic alveoli. Double-immunofluorescence (IF) showed that ANXA8 positive (+ve) cells were ER-alpha negative (−ve) and mostly quiescent, as defined by lack of Ki67 expression during puberty and mid-pregnancy, but not terminally differentiated with ~15% of ANXA8 +ve cells re-entering the cell cycle at the start of pregnancy (day 4.5). RT-PCR on RNA from FACS-sorted cells and double-IF showed that ANXA8+ve cells were a subpopulation of c-kit +ve luminal progenitor cells, which have recently been identified as the cells of origin of basal-like breast cancers. Over expression of ANXA8 in the mammary epithelial cell line Kim-2 led to a G0/G1 arrest and suppressed Ki67 expression, indicating cell cycle exit. Our data therefore identify ANXA8 as a potential mediator of quiescence in the normal mouse mammary ductal epithelium, while its expression in basal-like breast cancers may be linked to ANXA8’s association with their specific cells of origin

Sheathless hydrodynamic positioning of buoyant drops and bubbles inside microchannels

Particles, bubbles, and drops carried by a fluid in a confined environment such as a pipe can be subjected to hydrodynamic lift forces, i.e., forces that are perpendicular to the direction of the flow. We investigated the positioning effect of lift forces acting on buoyant drops and bubbles suspended in a carrier fluid and flowing in a horizontal microchannel. We report experiments on drops of water in fluorocarbon liquid, and on bubbles of nitrogen in hydrocarbon liquid and silicone oil, inside microchannels with widths on the order of 0.1–1 mm. Despite their buoyancy, drops and bubbles could travel without contacting with the walls of channels; the most important parameters for reaching this flow regime in our experiments were the viscosity and the velocity of the carrier fluid, and the sizes of drops and bubbles. The dependencies of the transverse position of drops and bubbles on these parameters were investigated. At steady state, the trajectories of drops and bubbles approached the center of the channel for drops and bubbles almost as large as the channel, carried by rapidly flowing viscous liquids; among our experiments, these flow conditions were characterized by larger capillary numbers and smaller Reynolds numbers. Analytical models of lift forces developed for the flow of drops much smaller than the width of the channel failed to predict their transverse position, while computational fluid dynamic simulations of the experiments agreed better with the experimental measurements. The degrees of success of these predictions indicate the importance of confinement on generating strong hydrodynamic lift forces. We conclude that, inside microfluidic channels, it is possible to support and position buoyant drops and bubbles simply by flowing a single-stream (i.e., “sheathless”) carrier liquid that has appropriate velocity and hydrodynamic properties.Chemistry and Chemical Biolog

Risk‐Treatment Paradox in the Selection of Transradial Access for Percutaneous Coronary Intervention

Background: Access site complications contribute to morbidity and mortality during percutaneous coronary intervention (PCI). Transradial arterial access significantly lowers the risk of access site complications compared to transfemoral arteriotomy. We sought to develop a prediction model for access site complications in patients undergoing PCI with femoral arteriotomy, and assess whether transradial access was selectively used in patients at high risk for complications. Methods and Results: We analyzed 17 509 patients who underwent PCI without circulatory support from 2008 to 2011 at 5 institutions. Transradial arterial access was used in 17.8% of patients. In those who underwent transfemoral access, 177 (1.2%) patients had access site complications. Using preprocedural clinical and demographic data, a prediction model for femoral arteriotomy complications was generated. The variables retained in the model included: elevated age (P<0.001), female gender (P<0.001), elevated troponin (P<0.001), decreased renal function or dialysis (P=0.002), emergent PCI (P=0.01), prior PCI (P=0.005), diabetes (P=0.008), and peripheral artery disease (P=0.003). The model showed moderate discrimination (optimism‐adjusted c‐statistic=0.72) and was internally validated via bootstrap resampling. Patients with higher predicted risk of complications via transfemoral access were less likely to receive transradial access (P<0.001). Similar results were seen in patients presenting with and without ST‐segment myocardial infarction and when adjusting for individual physician operator. Conclusions: We generated and validated a model for transfemoral access site complications during PCI. Paradoxically, patients most likely to develop access site complications from transfemoral access, and therefore benefit from transradial access, were the least likely to receive transradial access

Enhancement of Immune Response Against Bordetella spp. by Disrupting Immunomodulation

Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the respiratory tract of mice, its natural host, but did increase activation of the inflammasome pathway, and recruitment of inflammatory cells. The mutant lacking btrS recruited many more B and T cells into the lungs, where they rapidly formed highly organized and distinctive Bronchial Associated Lymphoid Tissue (BALT) not induced by any wild type Bordetella species, and a much more rapid and strong antibody response than observed with any of these species. Immunity induced by the mutant was measurably more robust in all respiratory organs, providing completely sterilizing immunity that protected against challenge infections for many months. Moreover, the mutant induced sterilizing immunity against infection with other classical bordetellae, including B. pertussis and B. parapertussis, something the current vaccines do not provide. These findings reveal profound immunomodulation by bordetellae and demonstrate that by disrupting it much more robust protective immunity can be generated, providing a pathway to greatly improve vaccines and preventive treatments against these important pathogens

Witnessed violence and youth behavior problems: A multi‐informant study.

Witnessed violence has significant negative consequences for youth behavior and mental health. However, many findings on the impact of witnessed violence have been based on a single informant. There is a general lack of consistency between caregiver and youth reports on both witnessed violence and behavioral problems. This study included data from both caregivers and youth and incorporated a multi-source analytic approach to simultaneously examine the association between youth witnessed violence and externalizing and internalizing behavior problems. Data from 875 caregivers and 812 youth were collected as part of the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). Findings showed that youth reported more witnessed violence than did their caregivers, and caregivers reported more externalizing and internalizing behavior problems than did youth. Further, the source of information had a significant impact on the association between witnessed violence and internalizing behaviors. These findings highlight the need to incorporate multiple sources and multi-informant analytic techniques to eliminate methodological limitations to understanding the effect of witnessed violence on youth behavioral problems

Alternative Oxidase Attenuates Cigarette Smoke-induced Lung Dysfunction and Tissue Damage

Cigarette smoke (CS) exposure is the predominant risk factor for the development of chronic obstructive pulmonary disease (COPD) and the third leading cause of death worldwide. We aimed to elucidate whether mitochondrial respiratory inhibition and oxidative stress are triggers in its etiology. In different models of CS exposure, we investigated the effect onlung remodeling and cell signaling of restoring mitochondrial respiratory electron flow using alternative oxidase (AOX), which bypasses the cytochrome segment of the respiratory chain. AOX attenuated CS-induced lung tissue destruction and loss of function in mice exposed chronically to CS for 9 months. It preserved the cell viability of isolated mouse embryonic fibroblasts treated with CS condensate, limited the induction of apoptosis, and decreased the production of reactive oxygen species (ROS). In contrast, the earlyphase inflammatory response induced by acute CS exposure of mouse lung, i.e., infiltration by macrophages and neutrophils and adverse signaling, was unaffected. The use of AOX allowed us to obtain novel pathomechanistic insights into CS-induced cell damage,mitochondrial ROS production, and lung remodeling. Our findings implicate mitochondrial respiratory inhibition as a key pathogenicmechanism of CS toxicity in the lung. We propose AOX as a novel tool to study CS-related lung remodeling and potentially to counteract CS-induced ROS production and cell damage