cssi/SciSciGPT-SciSciNet huggingface dataset:
An in vitro technique to study penetration of hamster oocyte-cumulus complexes by using physiological numbers of sperm

We have developed an inexpensive in vitro system for studying cumulus penetration and fertilization by using physiological numbers of sperm. This system simulates conditions believed to exist in vivo more closely than any in current usage. In this system, 1–100 hamster sperm are used to challenge fresh hamster oocyte-cumulus complexes (OCC). Only fresh (nonoviducal) OCC are used, as they present the most stringent challenge to sperm. Because sperm numbers are low, OCC do not disperse, and sperm can be studied microscopically during penetration of the cumulus oophorus and corona radiata. These conditions permit microscopic assessment of the sperm acrosome. Video tapes of experiments allow easy review and analysis of experiments. Results obtained employing this technique show that, in vitro, (1) capacitated, acrosome-intact hamster sperm can penetrate the extracellular matrix between cumulus cells and bind to the zona pellucida; (2) the “figure-eight motility” characteristic of hyperactivated hamster sperm swimming in culture medium is suppressed when sperm swim in the extracellular matrix between cumulus cells; and (3) fertilization occurs in capillary tubes when low numbers of sperm are used. The in vitro system that we have described will be useful in analyzing the mechanisms used by sperm to penetrate the cumulus and corona radiata and to clarify the role of the acrosomal enzymes in fertilization.
Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblasts

Cell-cell signaling roles for reactive oxygen species (ROS) generated in response to growth factors/cytokines in nonphagocytic cells are not well defined. In this study, we show that fibroblasts isolated from lungs of patients with idiopathic pulmonary fibrosis (IPF) generate extracellular hydrogen peroxide (H2O2) in response to the multifunctional cytokine, transforming growth factor-beta1 (TGF-beta1). In contrast, TGF-beta1 stimulation of small airway epithelial cells (SAECs) does not result in detectable levels of extracellular H2O2. IPF fibroblasts independently stimulated with TGF-beta1 induce loss of viability and death of overlying SAECs when cocultured in a compartmentalized Transwell system. These effects on SAECs are inhibited by the addition of catalase to the coculture system or by the selective enzymatic blockade of H2O2 production by IPF fibroblasts. IPF fibroblasts heterogeneously express alpha-smooth muscle actin stress fibers, a marker of myofibroblast differentiation. Cellular localization of H2O2 by a fluorescent-labeling strategy demonstrated that extracellular secretion of H2O2 is specific to the myofibroblast phenotype. Thus, myofibroblast secretion of H2O2 functions as a diffusible death signal for lung epithelial cells. This novel mechanism for intercellular ROS signaling may be important in physiological/pathophysiological processes characterized by regenerating epithelial cells and activated myofibroblasts.
Demographics and microbiology of otorrhea through patent tubes failing ototopical and/or oral antibiotic therapy.

Objectives. Posttympanostomy tube otorrhea (PTTO) results in significant health care cost and decreased satisfaction with care. The authors reviewed PTTO failing initial ototopical and/or oral antibiotic therapy and microbiology/susceptibility data from cultures.Study Design. Case series with chart review.Setting. A community university satellite ambulatory clinic and the outpatient clinic of a children’s hospital.Methods. Review of 202 patients with 228 discrete episodes of culture-positive otorrhea from January 2004 to January 2009.Results. PTTO occurred an average of 13 months after tube placement. Median otorrhea duration was 21 days (mean, 42 days). A mean of 1.6 visits (range, 1-6) to the pediatric otolaryngology office was required for PTTO resolution. Ototopical therapy was reported used in 198 of 228 (87%) episodes of otorrhea prior to pediatric otolaryngology visit. Nearly 50% of patients were prescribed at least 1 or more courses of systemic antibiotics. Staphylococcus aureus accounted for 52% ...
Gender-related group dynamics in problem-based learning : a retrospective study.

As problem-based learning (PBL) techniques play an increasingly important role in medical school curricula, programs will require an understanding of which variables enhance or inhibit learning. Through a retrospective study of an "experiment" in which male and female medical students were separated into single-gender tutorial groups, the authors describe gender differences in the styles of participation and subjective experi-ence of men and women in mixed-gender and single-gender tutorial groups. The women students noted an increase in their comfort level in the all-women tutorial group and felt that learning about their own styles in this group helped them participate more effec-tively in coed groups and later on in other professional settings. The authors make rec-ommendations concerning the implementation of PBL in medical school curricula.
Gender Equality in the Ivory Tower, and How Best to Achieve It

Both statistical and qualitative interview data confirm the on-going existence of gender inequality within American academia, with women both underrepresented and underpaid compared to their male counterparts. Surprisingly, what is needed to remedy this situation is not a secret. Most of the policies outlined in this article as good workable solutions are programs that have been tested and described in more than one study. Indeed, evidence suggests that when the nine strategies we identify here are fully implemented, as they have been at a few colleges and universities, the number of women on the faculty increases dramatically. The fact that we do not adopt these policies more widely in academia suggests not a lack of knowledge so much as apathy, prejudice, gender stereotypes, and cultural cues that end by depriving society of some of its best talent and energy.
User-centric design space exploration for heterogeneous network-on-chip platforms

In this paper, we present a design methodology for automatic platform generation of future heterogeneous systems where communication happens via the Network-on-Chip (NoC) approach. As a novel contribution, we consider explicitly the information about the user experience into a design flow which aims at minimizing the workload variance; this allows the system to better adapt to different types of user needs and workload variations. More specifically, we first collect various user traces from various applications and generate specific clusters using machine learning techniques. For each cluster of such user traces, depending on the architectural parameters extracted from high-level specifications, we propose an optimization method to generate the NoC system architecture. Finally, we validate the user-centric design space exploration using realistic traces and compare it to the traditional NoC design methodology.
Localization of 2',3'-cyclic nucleotide-3'-phosphohydrolase of rabbit brain by sedimentation in a continuous sucrose gradient.

— The enzyme 2′,3′-cyclic nucleotide-3′-phosphohydrolase (CNP) has been assayed in fractions from a continuous sucrose density gradient zonal centrifugation of rabbit brain homogenates. Basic protein (BP) was also assayed by a radioimmunomethod. Fractions were examined by SDS-polyacrylamide gel electrophoresis and by electron microscopy. These studies show that the major membrane fractions in the gradient differ greatly in the content of CNP and BP, and of high molecular weight proteins (HMW). The lightest membrane fractions contained numerous multilamellae, the highest content of BP and the lowest content of CNP and HMW, while the heaviest membrane fractions contained single membrane fragments and vesicles of unknown origin, the lowest content of BP and the highest content of CNP and HMW. The fraction containing the largest amount of membrane measured by turbidity, protein content, and water-washed dry weight contained only half the CNP specific activity of a denser fraction in the gradient. CNP specific activity in the lightest fractions was insignificant compared to that of denser fractions. Thus, we conclude that this enzyme may be absent from the typical multilamellar myelin structures but present in the single-membrane structures associated with myelin, such as the glial membrane and the paranodal segments of myelin adjacent to the axon. BP appears to occupy the opposite positions, highest in the multilamellae and lowest in the single-membrane structures of myelin. These studies do not exclude the possibility that CNP may not be bound to myelin membranes, but rather to a membrane of different origin. Evidence that this enzyme is a myelin-marker enzyme is circumstantial. Our evidence indicates the enzyme could be present either in a unique portion of myelin membranes or in another membrane structure.
An analytical model for support loss in micromachined beam resonators with in-plane flexural vibrations

This paper presents an analytical model for support loss in clamped–free (C–F) and clamped–clamped (C–C) micromachined beam resonators with in-plane flexural vibrations. In this model, the flexural vibration of a beam resonator is described using the beam theory. An elastic wave excited by the shear stress of the beam resonator and propagating in the support structure is described through the 2D elastic wave theory, with the assumption that the beam thickness (h) is much smaller than the transverse elastic wavelength (λT). Through the combination of these two theories and the Fourier transform, closed-form expressions for support loss in C–F and C–C beam resonators are obtained. Specifically, closed-form expression for the support loss in a C–C beam resonator is derived for the first time. The model suggests lower support quality factor (Qsupport) for higher order resonant modes compared to the fundamental mode of a beam resonator. Through comparison with experimental data, the validity of the presented analytical model is demonstrated. © 2003 Elsevier B.V. All rights reserved.
The Role of Evolutionary Intermediates in the Host Adaptation of Canine Parvovirus

The adaptation of viruses to new hosts is a poorly understood process likely involving a variety of viral structures and functions that allow efficient replication and spread. Canine parvovirus (CPV) emerged in the late 1970s as a host-range variant of a virus related to feline panleukopenia virus (FPV). Within a few years of its emergence in dogs, there was a worldwide replacement of the initial virus strain (CPV type 2) by a variant (CPV type 2a) characterized by four amino acid differences in the capsid protein. However, the evolutionary processes that underlie the acquisition of these four mutations, as well as their effects on viral fitness, both singly and in combination, are still uncertain. Using a comprehensive experimental analysis of multiple intermediate mutational combinations, we show that these four capsid mutations act in concert to alter antigenicity, cell receptor binding, and relative in vitro growth in feline cells. Hence, host adaptation involved complex interactions among both surface-exposed and buried capsid mutations that together altered cell infection and immune escape properties of the viruses. Notably, most intermediate viral genotypes containing different combinations of the four key amino acids possessed markedly lower fitness than the wild-type viruses.
High-speed chip-to-chip optical interconnect

An intraboard chip-to-chip optical interconnect has been demonstrated as a compatible and potentially manufacturable last step in the conventional multichip module process. Chip-to-chip optical communication at 1 Gb/s NRZ was achieved using an edge emitting laser, a flip-chip p-i-n photodetector and a photodefined polymer optical waveguide. >
TECHNIQUE ESTIMATING SEA SPRAY PRODUCTION RATE FOR GLOBAL CLIMATE MODELS FROM SATELLITE-DERIVED MEASURES OF OCEANIC WHITECAP COVERAGE

By combining laboratory-determined values for the number of sea spray droplets, per increment of droplet radius, that are produced during the decay of an oceanic whitecap of initial unit surface area, and values determined from both laboratory experiments and field observations for the e-folding time associated with the decay of individual oceanic whitecaps, with satellite-derived measures of the fraction of the sea surface covered at any instant by spilling wave crests (Stage A whitecaps), the number of sea spray droplets, per droplet radius increment, that are produced per unit time, per unit area of the ocean surface, can be estimated. This sea spray aerosol source function can be incorporated in any global climate model where the role of spray droplets in influencing maritime cloudiness, in affecting the over-ocean radiative balance, and in contributing to the sea-air moisture flux, need be explicitly parameterized
Quasi-Geostrophic Diagnosis of the Monsoon Depression of 5–8 July 1979

Abstract Quasi-geostrophic diagnosis of the fields of vertical motion and streamfunction tendency, based on wind analysis, was undertaken for the monsoon depression of 5–8 July 1979, a uniquely well-observed case during Summer MONEX. Wind analysis, in terms of streamfunction and velocity potential, was performed for data averaged in three layers of equal pressure depth front 1000 to 100 mb. The thermal stratification near the depression above 850 mb was approximately moist-adiabatic. The wind analyses showed that the basic zonal currents, westerly in the lower troposphere and easterly in the middle levels, weakened as the depression formed. Central vorticity increased rapidly on 5–6 July to a magnitude three times the Coriolis parameter. The center tilted toward the southwest with elevation. The quasi-geostrophic omega-equation was solved at the interfaces between layers, for a range of stabilities from the full dry-adiabatic value to 1% of it. Ascent west of the center for the near-neutral stability was ...
Mitral Stenosis and Aortic Atresia--A Risk Factor for Mortality After the Modified Norwood Operation in Hypoplastic Left Heart Syndrome.

Background There are conflicting reports regarding the importance of mitral stenosis and aortic atresia as a risk factor for Norwood mortality. This study reviews outcomes of this anatomic subgroup at our institution and examines the utility of preoperative cardiac catheterization and its correlation with clinical outcomes and pathology findings. Methods This is a single-center, retrospective review of hypoplastic left heart syndrome patients who underwent modified Norwood operation between October 2005 and May 2013. Results Fourteen of 74 hypoplastic left heart syndrome patients (19%) had mitral stenosis and aortic atresia. Operative mortality for MS/AA was 29% versus 7% for all other hypoplastic left heart syndrome anatomic subgroups ( p = 0.04). Although only 19% of the entire cohort, the mitral stenosis and aortic atresia subgroup constituted 50% of the total operative mortality and the only interstage deaths. Autopsies support myocardial ischemia as the mechanism of death. Although preoperative angiography defined the presence of ventriculo-coronary connections, it did not clearly risk stratify patients in regard to operative mortality. Conclusions Mitral stenosis and aortic atresia is a risk factor for perioperative myocardial ischemia and mortality. Further exploration of myocardial reserve is warranted.
The Ethical-Political Side of Schutz: His Contributions at the 1956 Institute on Ethics concerned with Barriers to Equality of Opportunity

Four previously unpublished texts authored or co-authored by Alfred Schutz are edited and introduced with an explication of contexts and significance that also incorporates thirty-three unpublished interventions by him during the general discussions at a 1956 ethics institute. A summary sketch of his ethical-political position there is then ventured.
Preclinical Activity of the Vascular Disrupting Agent OXi4503 against Head and Neck Cancer.

Vascular disrupting agents (VDAs) represent a relatively distinct class of agents that target established blood vessels in tumors. In this study, we examined the preclinical activity of the second-generation VDA OXi4503 against human head and neck squamous cell carcinoma (HNSCC). Studies were performed in subcutaneous and orthotopic FaDu-luc HNSCC xenografts established in immunodeficient mice. In the subcutaneous model, bioluminescence imaging (BLI) along with tumor growth measurements was performed to assess tumor response to therapy. In mice bearing orthotopic tumors, a dual modality imaging approach based on BLI and magnetic resonance imaging (MRI) was utilized. Correlative histologic assessment of tumors was performed to validate imaging data. Dynamic BLI revealed a marked reduction in radiance within a few hours of OXi4503 administration compared to baseline levels. However, this reduction was transient with vascular recovery observed at 24 h post treatment. A single injection of OXi4503 (40 mg/kg) resulted in a significant (p < 0.01) tumor growth inhibition of subcutaneous FaDu-luc xenografts. MRI revealed a significant reduction (p < 0.05) in volume of orthotopic tumors at 10 days post two doses of OXi4503 treatment. Corresponding histologic (H&E) sections of Oxi4503 treated tumors showed extensive areas of necrosis and hemorrhaging compared to untreated controls. To the best of our knowledge, this is the first report, on the activity of Oxi4503 against HNSCC. These results demonstrate the potential of tumor-VDAs in head and neck cancer. Further examination of the antivascular and antitumor activity of Oxi4503 against HNSCC alone and in combination with chemotherapy and radiation is warranted.
Incorporating Developmental Principles Into Clinical Care.

An 8-year-old is being treated for attention-deficit hyperactivity disorder (ADHD),with a positive response tomedication and behavioral management. Although the child’s academic performance has improved, the parents are concerned that the child does not appear to fully understand the importance of doing well at school, despite their parental explanations about college and careers. School assignments are done adequately, but the child spends no extra time on academic activities and refuses to participate in educationally related recreational activities, preferring to dress up and engage in imaginary play, often related to the child’s favorite movies. The scenarios are often quite involved and take considerable planning. The child often plays alone (although there is some playtime with two peers) and is uninterested in playing a team sport. Life at home has improved, with the child being less irritable and reactive. The parents state that the child has always been moody and has difficulty adjusting to change. Over the years, this has improved. The child generally seeks out the parents when distressed and responds positively to their suggestions. The parents are wondering whether the child’s ADHD is being adequately treated. They ask the psychiatrist whether there are additional treatment interventions to improve the child’s motivation and academic performance. The psychiatrist brings this case up in peer supervision for suggestions about how to respond.
PGE1 inhibited PMN attachment to air emboli in vivo during infusion of ZAP without preventing lung injury

Prostaglandin E1 (PGE1) treatment of neutrophils inhibits their adherence to substrates in vitro, including endothelial cell monolayers. Demonstration that PGE1 inhibits neutrophil adherence in vivo in the lung, however, is complicated by PGE1 effects on cells other than neutrophils, such as endothelial cells. To determine whether PGE1 inhibits neutrophil adherence properties in vivo, we used air emboli as intravascular targets for neutrophil attachment. Four experimental conditions were studied in anesthetized and awake sheep that were treated with 1) PGE1 and air emboli, 2) saline and air emboli, 3) PGE1 and zymosan-activated plasma (ZAP) + air emboli, and 4) saline and ZAP + air emboli. PGE1 (30 ng.kg-1.min-1) or saline was infused continuously 1 h before and 1 h during the infusion of air emboli (group 1; n = 13 sheep) or ZAP + air emboli (group 2; n = 13 sheep). The number of neutrophils (PMNs) attached to air emboli in four anesthetized sheep per condition was significantly less in sheep given PGE1 and ZAP + air emboli [8 +/- 3 (SD) PMNs/mm of embolus perimeter] than in the other three conditions (14–21 PMNs/mm; P less than 0.05). Repeated experiments in five awake sheep per group showed that PGE1 treatment did not prevent increased lung lymph protein clearance in either group compared with saline treatment. We conclude that PGE1 specifically inhibited attachment of ZAP-activated neutrophils to air emboli in vivo. The lack of pathophysiological protection suggests that PGE1-induced alterations in neutrophil attachment properties were independent of other cellular activation responses.
Inhibition of Heat Shock Protein 90 Prevents HIV Rebound

HIV evades eradication because transcriptionally dormant proviral genomes persist in long-lived reservoirs of resting CD4+ T cells and myeloid cells, which are the source of viral rebound after cessation of antiretroviral therapy. Dormant HIV genomes readily produce infectious virus upon cellular activation because host transcription factors activated specifically by cell stress and heat shock mediate full-length HIV transcription. The molecular chaperone heat shock protein 90 (Hsp90) is overexpressed during heat shock and activates inducible cellular transcription factors. Here we show that heat shock accelerates HIV transcription through induction of Hsp90 activity, which activates essential HIV-specific cellular transcription factors (NF-κB, NFAT, and STAT5), and that inhibition of Hsp90 greatly reduces gene expression mediated by these factors. More importantly, we show that Hsp90 controls virus transcription in vivo by specific Hsp90 inhibitors in clinical development, tanespimycin (17-(allylamino)-17-demethoxygeldanamycin) and AUY922, which durably prevented viral rebound in HIV-infected humanized NOD scid IL-2Rγ−/− bone marrow-liver-thymus mice up to 11 weeks after treatment cessation. Despite the absence of rebound viremia, we were able to recover infectious HIV from PBMC with heat shock. Replication-competent virus was detected in spleen cells from these nonviremic Hsp90 inhibitor-treated mice, indicating the presence of a tissue reservoir of persistent infection. Our novel findings provide in vivo evidence that inhibition of Hsp90 activity prevents HIV gene expression in replication-competent cellular reservoirs that would typically cause rebound in plasma viremia after antiretroviral therapy cessation. Alternating or supplementing Hsp90 inhibitors with current antiretroviral therapy regimens could conceivably suppress rebound viremia from persistent HIV reservoirs.
Children learning science through engineering: an investigation of four engineering-design-based curriculum modules

This research investigates the use of engineering design challenges as the basis for primary school science learning environments. We used pre-post tests to compare engineering-based students' science content gains to those of students using their district's typical science curriculum. Across the domains of animal adaptations, simple machines, material properties, and sound, the engineering-based science students showed significant pre-post learning gains, and for all domains except sound, their gains were significantly higher than those of comparison students.
Serum Protein Electrophoresis: A Comparison of the Use of Thin-layer Agarose Gel and Cellulose Acetate

Thin-layer agarose gel is a relatively new support medium for electrophoresis of serum proteins, but has not been critically evaluated or compared with any other medium. In this report, data for replicate and individual specimen analyses are compared with those obtained on cellulose acetate membranes. The data compare very well. Thin-layer agarose gel offers an advantage in the more distinct separation between beta-globulin and gammaglobulin.
Endothelium-dependent regulation of cerebrovascular tone by extracellular and intracellular ATP

ATP receptors and ATP-sensitive potassium channels (KATP) are expressed in vascular smooth muscle (VSM) and endothelial cells (EC). In isolated penetrating vessels, ATP caused a dilatation when applied intraluminally but not extraluminally. The actions of ATP were blocked by the nitric oxide (NO) synthesis inhibitor N omega-nitro-L-arginine (0.1 mM) but were only reduced by N-monomethyl-L-arginine (0.1 mM); responses to intraluminal ATP were also prevented by thapsigargin. The KATP opener (KCO) nicorandil (1 microM) caused an NO-independent vasodilatation when applied extraluminally and an NO-dependent response when applied intraluminally. Both responses were blocked by glibenclamide. EC-mediated responses to nicroandil were prevented by blockade of guanylate cyclase by LY-83583 (10 microM). The effects of nicorandil were mimicked by pinacidil (1-10 microM). Exposure of the endothelium to 500 microM cyanide and 0 mM glucose ("in vitro ischemia") caused a vasodilatation that was reduced by exposure to glibenclamide (5 microM). Blockade of NO synthase produced similar effects, suggesting that the ischemic dilation is mediated by KATP and NO. Our results suggest that both VSM and EC mediate the vascular responses induced by KCOs, whereas the dilatation induced by intraluminal ATP is mediated by the endothelium. The endothelium-dependent component of the in vitro ischemic vasodilatation is mediated by opening of endothelial KATP and subsequent release of NO.
Detergent Isolation Stabilizes and Activates the Shigella Type III Secretion System Translocator Protein IpaC

Abstract Shigella rely on a type III secretion system as the primary virulence factor for invasion and colonization of human hosts. Although there are an estimated 90 million Shigella infections, annually responsible for more than 100,000 deaths worldwide, challenges isolating and stabilizing many type III secretion system proteins have prevented a full understanding of the Shigella invasion mechanism and additionally slowed progress toward a much needed Shigella vaccine. Here, we show that the non-denaturing zwitterionic detergent N, N -dimethyldodecylamine N -oxide (LDAO) and non-ionic detergent n -octyl-oligo-oxyethylene efficiently isolated the hydrophobic Shigella translocator protein IpaC from the co-purified IpaC/IpgC chaperone-bound complex. Both detergents resulted in monomeric IpaC that exhibits strong membrane binding and lysis characteristics while the chaperone-bound complex does not, suggesting that the stabilizing detergents provide a means of following IpaC "activation" in vitro . Additionally, biophysical characterization found that LDAO provides significant thermal and temporal stability to IpaC, protecting it for several days at room temperature and brief exposure to temperatures reaching 90°C. In summary, this work identified and characterized conditions that provide stable, membrane active IpaC, providing insight into key interactions with membranes and laying a strong foundation for future vaccine formulation studies taking advantage of the native immunogenicity of IpaC and the stability provided by LDAO.
A Review of Methodologies for Analyzing Websites

This chapter is an overview of the process of Web analytics for Websites. It outlines how basic visitor information such as number of visitors and visit duration can be collected using log files and page tagging. This basic information is then combined to create meaningful key performance indicators that are tailored not only to the business goals of the company running the Website, but also to the goals and content of the Website. Finally, this chapter presents several analytic tools and explains how to choose the right tool for the needs of the Website. The ultimate goal of this chapter is to provide methods for increasing revenue and customer satisfaction through careful analysis of visitor interaction with a Website.
The next-generation nicotine vaccine: a novel and potent hybrid nanoparticle-based nicotine vaccine

Owing to the urgent need for more effective treatment against nicotine addiction, a hybrid nanoparticle-based nicotine vaccine (NanoNiccine) was developed in this study. NanoNiccine was composed of a poly(lactide-co-glycolide) acid (PLGA) core, keyhole limpet hemocyanin (KLH) as an adjuvant protein enclosed within the PLGA core, a lipid layer, and nicotine haptens conjugated to the outer surface of the lipid layer. In contrast to the traditional nicotine vaccine, NanoNiccine is not a nicotine-protein conjugate vaccine. Instead, the nicotine hapten and protein are separately located in the nanostructure to minimize antibody production towards KLH. The cellular uptake study demonstrated that NanoNiccine was ideal for internalization and processing by dendritic cells (DCs). Mice immunized with NanoNiccine produced much lower IgG level against KLH as compared to that immunized with the traditional nicotine-KLH (Nic-KLH) vaccine. In addition, NanoNiccine achieved up to a 400% higher titer of anti-nicotine IgG than the positive control, Nic-KLH. Additionally, the Th1/Th2 index of NanoNiccine suggested that the immune response induced by NanoNiccine was antibody response dominant. Furthermore, NanoNiccine was found to be safe in mice.
The Reality of "Real-World" Data: More Questions Than Answers.

In this issue of the Journal , Chan et al. [(1)][1] compare the real-world efficacy and safety of 2 non–vitamin K antagonist oral anticoagulant agents (NOACs), rivaroxaban and dabigatran, with warfarin and with each other in Asian patients with atrial fibrillation (AF) in a retrospective cohort
A theoretical basis for a nanomolar critical oxygen concentration

When aerobic microbes deplete oxygen sufficiently, anaerobic metabolisms activate, driving losses of fixed nitrogen from marine oxygen minimum zones. Biogeochemical models commonly prescribe a 1–10 μM critical oxygen concentration for this transition, a range consistent with previous empirical and recent theoretical work. However, the recently developed STOX sensor has revealed large regions with much lower oxygen concentrations, at or below its 1–10 nM detection limit. Here, we develop a simplified metabolic model of an aerobic microbe to provide a theoretical interpretation of this observed depletion. We frame the threshold as O2*, the subsistence oxygen concentration of an aerobic microbial metabolism, at which anaerobic metabolisms can coexist with or outcompete aerobic growth. The framework predicts that this minimum oxygen concentration varies with environmental and physiological factors and is in the nanomolar range for most marine environments, consistent with observed concentrations. Using observed grazing rates to calibrate the model, we predict a minimum oxygen concentration of order 0.1–10 nM in the core of a coastal anoxic zone. We also present an argument for why anammox may be energetically favorable at a higher oxygen concentration than denitrification, as some observations suggest. The model generates hypotheses that could be tested in the field and provides a simple, mechanistic, and dynamic parameterization of oxygen depletion for biogeochemical models, without prescription of a fixed critical oxygen concentration.
Predictors of extracapsular extension in HPV-associated oropharyngeal cancer treated surgically

Abstract Objectives Extracapsular extension (ECE) in cervical metastatic lymph nodes remains an indication for adding chemotherapy for patients with oropharyngeal squamous cell carcinoma (OPSCC). The aim of this study is to identify specific imaging characteristics on computed tomography (CT) scan that are predictive of ECE in order to better risk stratify patients preoperatively. Materials and methods A single cohort study was performed using a prospectively collected database of patients with HPV-related OPSCC who underwent transoral robotic surgery with cervical lymphadenectomy. CT scans were assessed for the presence of multiple imaging characteristics, including lymph node size, number of nodes positive, cystic appearance, and border irregularity. Univariable and multivariable analyses were performed to analyze each variable’s predictability of pathologic ECE. Results 100 patients underwent TORS with cervical lymphadenectomy for OPSCC from 2010 to 2015. Ninety-one percent (21/23) of patients with 3 or more radiologically suspicious nodes were found to have pathologic ECE, which was a significantly greater proportion than patients with fewer suspicious nodes (p Conclusion and relevance The presence of 3 or more radiologically suspicious lymph nodes on CT scan has a 91% PPV for any histologic evidence of ECE. The absolute number of radiographically suspicious lymph node metastases may be a useful method for risk-stratifying patients for the presence of ECE.
Bone Weathering of Juvenile-Sized Remains in the North Carolina Piedmont

In decomposition studies, soft tissue decay and the effects of the environment on its processes and timing have been the primary focus. Decompositional changes to skeletal material, often called bone weathering, have been observed in far fewer research studies, most notably Behrensmeyer’s (Paleobiology 4:150–162, 1978) foundational project that first described the process and time frame for hard tissue decay. While other studies have followed, all have noted that the rate and the process of decay are dependent on the local environmental factors affecting the skeletal material, an issue that is also well known in soft tissue decomposition research. While much of the bone weathering studies are long-term and often use adult elements, this study adds to the literature by focusing on short-term changes occurring within a year to juvenile domestic pigs in the central Piedmont region of North Carolina. In this study, juvenile domestic pigs, Sus scrofa (n = 7), were used as proxies for human children because of their similarity in size and immaturity of the skeletal elements. Observations took place over an 8-month period; two fleshed pigs (n = 2) were placed at the beginning of the observational period, while the other five (n = 5) had been in the research field for at least 3 months prior to the beginning of the project. The study found that, while all skeletal elements remained largely intact, specific elements were more affected by different types of weathering. Long, tubular bones, including long bones, metacarpals, metatarsals, and phalanges, were more prone to flaking of the outer layers of cortical bone, while long bones, vertebrae, and ribs were more likely to have loss of bone at the articular facets, leading to exposure of interior trabecular bone. The location of the project, largely underutilized in forensic research, shares similar environmental factors with other large areas of the American South. Consequently, the results could be applied to the broader southeastern United States.
Peptide Inhibitors Targeting the Neisseria gonorrhoeae Pivotal Anaerobic Respiration Factor AniA.

Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which is highly prevalent worldwide and has a major impact on reproductive and neonatal health. The superbug status of N. gonorrhoeae necessitates the development of drugs with different mechanisms of action. Here, we focused on targeting the nitrite reductase AniA, which is a pivotal component of N. gonorrhoeae anaerobic respiration and biofilm formation. Our studies showed that gonococci expressing AniA containing the altered catalytic residues D137A and H280A failed to grow under anaerobic conditions, demonstrating that the nitrite reductase function is essential. To facilitate the pharmacological targeting of AniA, new crystal structures of AniA were refined to 1.90-A and 2.35-A resolutions, and a phage display approach with libraries expressing randomized linear dodecameric peptides or heptameric peptides flanked by a pair of cysteine residues was utilized. Biopanning experiments led to the identification of 29 unique peptides, with 1 of them, C7-3, being identified multiple times. Evaluation of their ability to interact with AniA using enzyme-linked immunosorbent assay and computational docking studies revealed that C7-3 was the most promising inhibitor, binding near the type 2 copper site of the enzyme, which is responsible for interaction with nitrite. Subsequent enzymatic assays and biolayer interferometry with a synthetic C7-3 and its derivatives, C7-3m1 and C7-3m2, demonstrated potent inhibition of AniA. Finally, the MIC50 value of C7-3 and C7-3m2 against anaerobically grown N. gonorrhoeae was 0.6 mM. We present the first peptide inhibitors of AniA, an enzyme that should be further exploited for antigonococcal drug development.
Stem cell therapy for reconstruction of alveolar cleft and trauma defects in adults: A randomized controlled, clinical trial.

Background Stem cell therapy with bone marrow-derived mesenchymal stem cells is a promising tissue engineering strategy to promote regeneration of craniofacial bone. Purpose To determine whether cell therapy with ex vivo expanded stem cell populations would be safe and efficacious in the regeneration of large alveolar defects in patients with a history of cleft palate or craniofacial trauma. Materials and Methods Eighteen patients (10 patients with traumatic injury and 8 patients with cleft palate) presenting with missing teeth associated with horizontal alveolar bone deficiencies were included in this randomized controlled clinical trial. Patients were randomized to receive either conventional autogenous block grafts or stem cell therapy. After a healing period of 4 months the treated sites were re-entered and the bone width re-assessed prior to implant placement. Implant stability was evaluated through torque testing of the implant upon insertion and at 6 months postloading. Results The mean gain in bone width was 1.5 ± 1.5 mm in the stem cell therapy group and 3.3 ± 1.4 mm in the control group. Overall, bone gain was higher in trauma patients as compared to patients with cleft palate, for both the control and the stem cell therapy groups. Most postoperative complications were wound dehiscences and incision line openings. Implants were placed successfully in 5 out of 10 patients in the stem cell therapy group and in all 8 patients in the control group. One implant from the control/cleft palate group failed before loading, while the rest of the implants were loaded successfully and remained stable at 6 months. The patients who did not receive implants were re-treated with autogenous block bone graft. Conclusion The ability of stem cells to treat large alveolar defects is safe, yet, their ability to completely reconstitute large alveolar defects is limited. This approach requires further optimization to meet the outcomes seen using current methods to treat large defects, particularly those resultant of cleft palate.
Effect of BST film thickness on the performance of tunable interdigital capacitors grown by MBE

Voltage-tunable, interdigital capacitors (IDCs) were fabricated on Ba0.29Sr0.71TiO3 grown by hybrid molecular beam epitaxy (MBE). In this growth technique, we utilize the metal-organic precursor titanium tetraisopropoxide rather than solid-source Ti as with conventional MBE. Two samples of varying BaxSr(1−x)TiO3 (BST) thicknesses were fabricated and analyzed. High-quality, epitaxial Pt electrodes were deposited by sputtering from a high-purity Pt target at 825 °C. The Pt electrodes were patterned and etched by argon ion milling, passivated with reactively sputtered SiO2, and then metallized with lift-off Ti/Au. The fabricated devices consisted of two-port IDCs embedded in ground-signal-ground, coplanar waveguide (CPW) transmission lines to enable radio-frequency (RF) probing. The sample included open and thru de-embedding structures to remove pad and CPW parasitic impedances. Two-port RF scattering (S) parameters were measured from 100 MHz to 40 GHz while DC bias was stepped from 0 V to 100 V. The IDCs ex...
A reformulated model of barriers to parental involvement in education: comment on Hornby and Lafaele (2011)

In a 2011 article in this journal, Hornby and Lafaele provided a comprehensive model to understand barriers that may adversely impact effectiveness of parental involvement (PI) in education. The pr...
Clustering: Some Nonstandard Approaches

The notion of clusters sparks interest in many scientists, leading the way to numerous taxonomies relevant to the descriptive part of science. Attribute correlations produce clusters of variables. Local spatial autocorrelation statistics produce clusters of hot and cold spots on a geographic map. Agglomeration economies and spatial externalities produce clusters of economic activities in a region/nation. But contemporary cluster analysis is more an art than a science. For example, a standard deck of playing cards can be clustered in various equally meaningful ways: by suits, by faces/non-faces, or by values. This chapter seeks to establish a more trustworthy foundation for cluster analysis in spatial statistics/econometrics.
Towards 20-watt continuous wave quantum cascade lasers

Significant increase in continuous wave optical power from a single quantum cascade laser (QCL), beyond its current record of 5W, will likely require power scaling with active region lateral dimensions. Active region overheating presents a major technical problem for such broad area devices. Laser thermal resistance can be reduced and laser self-heating can be suppressed by significantly reducing active region thickness, i.e. by reducing number of active region stages and by reducing thickness of each stage in the cascade. The main challenge for quantum cascade lasers with a “thin” active region is to ensure that optical power emitted per active region unit area stays high despite the reduction in active region thickness, a condition critical for the power scaling. Experimental data demonstrating a multi-watt continuous wave operation for broad area QCLs, as well as various aspects of bandgap engineering, waveguide design, and thermal design pertinent to the broad area configuration, are discussed in this manuscript. The critical differences in broad-area laser design between mid-wave and long-wave QCLs is highlighted. Finally, semi-empirical model projections showing that the goal of reaching 20W from a single emitter is realistic is presented.
Finite element modeling of contact conditions in multibody system dynamics

In this paper a new method is developed for the dynamic analysis of contact conditions in flexible multibody systems undergoing a rolling type of motion. The relative motion between the two contacting bodies is treated as a constraint condition describing their kinematic and geometric relations. Equations of motion of the system are presented in a matrix form making use of Kane's equations and finite element method. The method developed has been implemented in a general purpose program called DARS and applied to the simulation and analysis of a rotating wheel on a track. Both the bodies are assumed flexible and discretized using a three dimensional 8-noded isoparametric elements. The time variant constraint conditions are imposed on the nodal points located at the peripheral surfaces of the bodies under consideration. The simulation is carried out under two different boundary conditions describing the support of the track. The subsequent constraint forces associated with the generalized coordinates of the system are computed and plotted. The effects of friction are also discussed.
Interface Separation in Residually-Stressed Thin-Film Structures

Plasticity is a significant contributor to the interfacial fracture resistance of multilayer thin-film structures containing ductile layers. Salient parameters affecting plasticity contributions to interfacial fracture energy including the ductile layer thickness, yield strength, and the maximum cohesive stress governing interface separation, have been reported. However, the effects of residual stresses in the thin-film layers on such plasticity contributions have not been considered. We explore the effect of residual stresses on debonding with particular attention to the relationship between the stress state in both ductile and elastic layers and the resulting macroscopic debond energy. Using multiscale simulations it is shown that residual thin-film stresses can alter plasticity in the ductile layer and significantly influence the macroscopic fracture energy. A simple yield-based model to account for this behavior is proposed.
Sticky hydrophobic behavior of cellulose substrates impregnated with alkyl ketene dimer (AKD) via sub- and supercritical carbon dioxide

Abstract Cellulose fibers were impregnated with alkyl ketene dimer (AKD) dissolved in n-heptane and carbon dioxide via sub- and supercritical impregnation techniques. The mechanistic pathways and hydrophobic performance at short and long times were investigated by contact angle (CA) analysis, scanning electron microscopy (SEM) with micrographs analyzed using Image-Pro Premier, and Fourier Transform Infrared (FTIR) analysis. The sizing development was significant after two days of treatment, and hydrophobic performance became uniform after two weeks regardless of the impregnation conditions investigated. Samples prepared at 100 and 200 bar produced more rapid development than those at higher and lower impregnation pressures, with the average CA at 200 bar and 21 °C being 140 ± 5°. ‘Sticky’ hydrophobicity was observed on surfaces treated at 200 and 250 bar at long times (> 140 days), and adhesive forces between the droplet (>20 μL) and surface were observed at surface tilt angles between 0 – 180°. SEM micrographs of the impregnated samples showed a reduction in substrate pore-size area (PSA) as hydrophobicity developed with time. There was little evidence of reaction-based sizing as the characteristic ketone and ester peaks were not observed in FTIR studies. The lactone ring remained intact. The 200 bar sample showed highest peak intensity for various hydrocarbon bonds observed – suggesting the optimal solubility of AKD in supercritical carbon dioxide (scCO2). Spreading of AKD across the fiber surfaces appeared to be the main sizing pathway, and identification of hydrogen bonding between AKD and cellulose fibers suggested a possible attachment method.