cssi/SciSciGPT-SciSciNet huggingface dataset:
Specific recruitment of circulating angiogenic cells using biomaterials as filters.

Abstract Endogenous recruitment of circulating angiogenic cells (CACs) is an emerging strategy to induce angiogenesis within a defect site, and multiple recent strategies have deployed soluble protein releasing biomaterials for this purpose. However, the way in which the design of biomaterials affects CAC recruitment and invasion are poorly understood. Here we used an enhanced-throughput cell invasion assay to systematically examine the effects of biomaterial design on CAC recruitment. The screens co-optimized hydrogel presentation of a stromal-derived factor-1α (SDF-1α) gradient, hydrogel degradability, and hydrogel stiffness for maximal CAC invasion. We also examined the specificity of this invasion by assessing dermal fibroblast, mesenchymal stem cell, and lymphocyte invasion individually and in co-culture with CACs to identify hydrogels specific to CAC invasion. These screens suggested a subset of MMP-degradable hydrogels presenting a specific range of SDF-1α gradient slopes that induced specific invasion of CACs, and we posit that the design parameters of this subset of hydrogels may serve as instructive templates for the future design of biomaterials to specifically recruit CACs. We also posit that this design concept may be applied more broadly in that it may be possible to utilize these specific subsets of biomaterials as “filters” to control which types of cell populations invade into and populate the biomaterial. Statement of Significance The recruitment of specific cell types for cell-based therapies in vivo is of great interest to the regenerative medicine community. Circulating angiogenic cells (CACs), CD133+ cells derived from the blood stream, are of particular interest for induction of angiogenesis in ischemic tissues, and recent studies utilizing soluble-factor releasing biomaterials to recruit these cells in vivo show great promise. However, these studies are largely “proof of concept” and are not systematic in nature. Thus, little is currently known about how biomaterial design affects the recruitment of CACs. In the present work, we use a high throughput cell invasion screening platform to systematically examine the effects of biomaterial design on circulating angiogenic cell (CAC) recruitment, and we successfully screened 263 conditions at 3 replicates each. Our results identify a particular subset of conditions that robustly recruit CACs. Additionally, we found that these conditions also specifically recruited CACs and excluded the other tested cells types of dermal fibroblasts, mesenchymal stem cells, and lymphocytes. This suggests an intriguing new role for biomaterials as “filters” to control the types of cells that invade and populate that biomaterial.
Unmet Expectations in Alzheimer's Family Caregiving: Interactional Characteristics Associated With Perceived Under-Contribution.

Background and objectives Perceptions about family members not contributing enough to caregiving are documented to create psychological stress among caregivers. This study investigated whether individuals' perception that family members are under-contributing in caregiving processes was associated with their psychological well-being and explored the factors that may contribute to such perception borrowing concepts from a previous study: malfeasance, nonfeasance, and uplift. Research design and methods Seventy-two members of 30 families recruited through residential and adult daycare settings provided information about 960 familial network members (e.g., family, friends). Perceived levels of participation in caregiving about each network member, whether the level met respondents' expectations, and interactions representing malfeasance, nonfeasance, and uplift were assessed. Results Number of family members respondents identified as under-contributing in caregiving was associated with higher, whereas numbers of family participating in caregiving and supportive staff were associated with lower distress (Center for Epidemiologic Studies Depression Scale [CES-D]). Factor analyses identified a set of social interactions among familial network members capturing three constructs: malfeasance, nonfeasance, and uplift. Network members for whom respondents reported higher levels of nonfeasance were more likely to be identified as under-contributing in direct care (odds ratio [OR] = 1.92), care decision making (OR = 1.89), and social support (OR = 1.74) compared with those identified as contributing enough. Members with higher levels of malfeasance were more likely to be identified as under-contributing in direct care (OR = 1.19) than those identified as contributing enough. Discussion and implications Social interactions characterized as nonfeasance may explain the perception of unmet expectations in caregiving within families and may represent a potential focus of family-level interventions.
Rational Solvent Selection for Pharmaceutical Impurity Purge

This study focuses on the development of computational impurity purge factor to enable rational solvent selection for purification of pharmaceutical compounds via recrystallization. Three purge factors have been proposed under SLE thermodynamic consideration based on two properties: impurity partition coefficient between solvent and crystalline pharmaceutical, and thermodynamic solubility of the crystalline pharmaceutical. A limited testing of the purge factors against experimental observations was performed, using COSMO-RS approach as implemented in the COSMOtherm software. Good and superior performance of the purge factor proportional to a difference between the impurity partition coefficient and the crystalline pharmaceutical solubility was demonstrated. As a result, a virtual solvent screening based on that factor is proposed to be used to guide selection of preferred solvents for impurity purge via recrystallization.
Nationalist Populism Is Not an Enemy

The recent history of American and European politics has been marked by the ascension of right-wing populism, evidenced in public support for Donald Trump, Marine Le Pen, several right-wing political parties throughout Europe, and the Brexit referendum. This chapter first outlines the defining traits of populism, especially in contrast to globalism, and argues that liberalism offers an insufficient response to the populist fever, as the individualism endorsed by liberals does not soothe the wounded sense of community that leaves the populist estranged. For this reason, the chapter argues, elements of communitarianism are needed to offer effective and acceptable guiding principles to quell radicalism and xenophobia, ones that would address typical populist issues: free trade, immigration, and rights. The chapter concludes by acknowledging that liberal and communitarian positions may come into conflict, and thus proposes a method to reconcile competing principles to protect individual rights and shore up the common good.
Theoretical modelling and prediction of surface roughness for hybrid additive–subtractive manufacturing processes

Hybrid additive–subtractive manufacturing processes are becoming increasingly popular as a promising solution to overcome the current limitations of Additive Manufacturing (AM) technology and impro...
Drug-eluting stents versus bare-metal stents in saphenous vein grafts: a double-blind, randomised trial

Summary Background Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions. Methods Patients were recruited to our double-blind, randomised controlled trial from 25 US Department of Veterans Affairs centres. Eligible participants were aged at least 18 years and had at least one significant de-novo SVG lesion (50–99% stenosis of a 2·25–4·5 mm diameter SVG) requiring percutaneous coronary intervention with intent to use embolic protection devices. Enrolled patients were randomly assigned, in a 1:1 ratio, by phone randomisation system to receive a DES or BMS. Randomisation was stratified by presence or absence of diabetes and number of target SVG lesions requiring percutaneous coronary intervention (one or two or more) within each participating site by use of an adaptive scheme intended to balance the two stent type groups on marginal totals for the stratification factors. Patients, referring physicians, study coordinators, and outcome assessors were masked to group allocation. The primary endpoint was the 12-month incidence of target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularisation. The DIVA trial is registered with ClinicalTrials.gov, number NCT01121224. Findings Between Jan 1, 2012, and Dec 31, 2015, 599 patients were randomly assigned to the stent groups, and the data for 597 patients were used. The patients' mean age was 68·6 (SD 7·6) years, and 595 (>99%) patients were men. The two stent groups were similar for most baseline characteristics. At 12 months, the incidence of target vessel failure was 17% (51 of 292) in the DES group versus 19% (58 of 305) in the BMS group (adjusted hazard ratio 0·92, 95% CI 0·63–1·34, p=0·70). Between-group differences in the components of the primary endpoint, serious adverse events, or stent thrombosis were not significant. Enrolment was stopped before the revised target sample size of 762 patients was reached. Interpretation In patients undergoing stenting of de-novo SVG lesions, no significant differences in outcomes between those receiving DES and BMS during 12 months of follow-up were found. The study results have important economic implications in countries with high DES prices such as the USA, because they suggest that the lower-cost BMS can be used in SVG lesions without compromising either safety or efficacy. Funding US Department of Veterans Affairs Cooperative Studies Program.
Does Reverse Triiodothyronine Testing Have Clinical Utility? An Analysis of Practice Variation Based on Order Data from a National Reference Laboratory.

Background: Clinical laboratories are under pressure to increase value by improving test utilization. The clinical utility of reverse triiodothyronine (rT3) is controversial. A study was conducted ...
Tricuspid valvulectomy without replacement: Twenty years’ experience

Since September 1970, we have operated on 55 patients with intractable right-sided endocarditis. All patients were addicted to heroin. Fifty-three underwent tricuspid valvulectomy without replacement and in addition two had pulmonic valve excision. Twenty-four patients (49%) returned to their drug addiction. Six patients (11%) required prosthetic heart valve insertion 2 days to 13 years later for medically refractory right-sided heart failure, and four of these died. Overall, 16 patients (29%) died, six (11%) within 45 days after the tricuspid valvulectomy. One (2%) of these deaths was related to the operation and five were due to uncontrollable infection. Ten (18%) deaths occurred 9 months to 13 years after the tricuspid valvulectomy. Nine were due to drug addiction and one to progressive right ventricular failure 2 months after prosthetic heart valve insertion and 10 years after the initial valve removal. Of the 39 patients who are alive, 37 (67%) have not required prosthetic heart valve insertion. From our observations we reached the following conclusions: (1) Drug addiction is a recurrent and lethal disease. Among these patients, tricuspid valvulectomy without replacement is the operation of choice for the management of intractable right-sided endocarditis; (2) after tricuspid valvulectomy without replacement, only six of 55 patients (11%) had required prosthetic heart valve insertion to control medically refractory right-sided heart failure; (3) in a small percentage of patients the absence of the tricuspid valve may lead to severe and permanent impairment of right ventricular function.
The Historical Abundance of Cod on the Nova Scotian Shelf

Only a generation ago marine scientists, fishery managers, and maritime historians shared the popular assumption that diminished fish stocks and damaged marine ecosystems were lamentable artifacts of the late twentieth century, of synthetic filaments, fish finding sonar, and electronic navigational systems. It seemed highly unlikely that historic sailing fleets could have depleted naturally abundant fish populations with simple hooks, hemp line, and handmade nets.
Causes of decreased phase transition temperature in selenite cataract model.

Purpose. Lenses from selenite-treated animals develop reversible «cold cataract» at a lower temperature than is required for lenses from age-matched control animals. This unexplained, stabilized phase transition is readily observed in intact lenses 36 to 48 hours after treatment and occurs in lenses before the appearance of the irreversible nuclear opacity observed 72 to 96 hours after treatment. The objective of this study was to investigate factors that may be responsible for this difference. Methods. Preweanling rats were injected with sodium selenite. Lens extracellular water volume was measured using 14 C-inulin. Free amino acids were analyzed using precolumn derivatization and high performance liquid chromatography. Soluble protein was isolated from lenses of control, and treated animals and temperature-dependent changes in light scattering were measured at 490 nm. Results. Lens extracellular water was increased by the selenite treatment, with a concurrent 10% decrease in intracellular volume. Solutions of soluble protein from lenses of selenite-treated animals after postinjection hours 24 and 48 had higher critical phase transition temperatures (T c ) compared to similar proteins from control lenses. From 24 to 72 hours after injection, the free amino acid content of the lens increased 42%. Taurine levels were unchanged over the same period. The addition of 7 mM glycine and 7 mM proline to solutions of soluble protein (96 mg ml -1 ) decreased the phase transition temperature. Taurine (14 mM) had a similar effect. Combining taurine and the glycine plus proline solutions had an additive effect in lowering the T c . Conclusions. Increases in free amino acid concentration occur in lenses in response to the stress imposed by a systemic dose of selenite. The altered polyion content in lenses from selenite-treated animals, before nuclear cataract formation, contributes to the greater thermal stability of transparency in these lenses, thus lowering the temperature at which «cold cataract» forms
Resilience of the Brain and Body

Abstract “Resilience” can be defined as the ability to achieve a successful outcome in the face of adversity. This is particularly relevant to the brain, which is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor, which promote adaptation (“allostasis”) but also contribute to pathophysiology (“allostatic load/overload”) when overused and dysregulated. The adult, as well as developing, brain possess a remarkable ability to show structural and functional plasticity and resilience in response to stressful and other experiences, including neuronal replacement, dendritic remodeling, and synapse turnover. Yet, the life course is a “one-way street” and gene expression is continually changing via epigenetic mechanisms; and one cannot “roll back the clock.” Thus, when one speaks of “resilience,” we must think of “redirection.” The purpose of this chapter is to put the concept of resilience into the context of the reciprocal communication between the brain and the body via neuroendocrine, autonomic, immune, and metabolic mechanisms viewed over the life course and to discuss strategies in interventions to promote brain and body health.
Commercializing MEMS--too fast or too slow? (Same as Vols. 2880 and 2881, p. 12)

MEMS as a technology base is coming of age, butas in any vital process growing pains occur. Commercializing MEMS is simultaneously viewed asagonizingly slow by many ofits promoters and lightingly quick by many companies whose products are being replaced with MEMS based substitutes. This effort ties current efforts in market analysis, technology evaluations, competency based strategy in an effort to understand the pace ofMEMS commercialization.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
The Calcium Culprit: A Case of Denosumab-induced Hypocalcemia

Denosumab is a fully human monoclonal antibody which is used to treat osteoporosis and has been shown to cause hypocalcemia in patients with underlying prostatic and bone malignancies, renal impairment, postmenopausal state, and/or vitamin D deficiency. We present a case of a male patient, with a past medical history negative for the aforementioned conditions, who presented with right shoulder pain and was found to be severely hypocalcemic secondary to denosumab.
A Data-Cleaning Approach to Robust Multisensor Detection of Improper Signals

We consider the problem of detecting the presence of an improper complex-valued signal, common among two or more sensors (channels), in the presence of spatially independent, colored improper noise and additive outliers. A source of improper noise is in-phase/quadrature-phase imbalance during down-conversion of bandpass noise to baseband at the receiver. For clean data (i.e., known to be outlier free), a nonparametric binary hypothesis testing formulation in frequency-domain, utilizing the discrete Fourier transform of an augmented measurement sequence, has been proposed in the literature, and it results in a generalized likelihood ratio test (GLRT). In this paper we robustify this approach against additive outliers in the data, using a data-cleaning approach. Using some existing robust estimators of multivariate scatter, we first detect the outliers, and subsequently remove and replace them using vector median filtering to yield cleaned data. The existing GLRT is then applied to the cleaned data. The approach is illustrated via simulations. The considered problem has applications in diverse areas including spectrum sensing for cognitive radio.
Glitazone loaded fat enhances adiponectin production and inhibits breast cancer cell proliferation

Obesity and diabetes are both associated risk factors for developing breast cancer and poor patient outcomes. Adipose cells are an important endocrine system and are the main producer of adiponectin, with lean patients having higher circulating levels. Patients with diabetes are often treated with thiazolidinediones, glitazones, which also increase adiponectin production. Importantly high circulating levels of adiponectin and treatment with glitazone are associated with increased breast cancer patient survival. This study investigates the potential of using adipose tissue laden with glitazones to act as a drug depot, increase adiponectin levels, and locally release glitazones to inhibit breast cancer cell proliferation. The breast cancer cell lines MCF-7 and MBA-MD-231, and the normal breast epithelial cell line MCF-10A were exposed to media containing a range of concentrations of recombinant adiponectin, pioglitazone, or conditioned media obtained from pioglitazone laden adipose tissue to determine the impact of the different treatments on cell proliferation. The MCF-7 cells demonstrated the greatest reduction in proliferation upon exposure to adiponectin and pioglitazone with lower reductions observed in the MDA-MD-231 and MCF-10a cell lines. All three cell lines exhibited reductions in proliferation in the presence of pioglitazone loaded adipose tissue. Additionally, adiponectin and pioglitazone levels were higher in the media from glitazone loaded adipose tissue. Drug loaded adipose tissue could potentially be used to deliver adiponectin and glitazone to breast cancer cells and inhibit proliferation. Future research will examine the potential efficacy of this treatment approach in vivo.
An Exposé of Canadian “Abandoned Vessels & Derelicts” Through a Legal Analysis of Doctrinal Silos

“Abandoned vessels and derelicts” have been on the Canadian scene since 2011 and in the past year or so, some of the most celebrated vessels such as the MV Miner, the Kathryn Spirit and the MV Farley Mowat have made their way from small online newswires to major national headlines. Although federal authorities have managed to dispose some of those vessels, the issue continues to remain at the epicentre of debate and discussion. With this exposure, followed by governmental debates and discussions, surfaced the question of responsibility for managing these so-called “abandoned vessels”, which is also sporadically referred to simply as “derelicts”. Responsibilities associated with the management of Canadian “abandoned vessel and derelict” have consistently proven to be a predicament over the last few years and a matter of debate for years among all levels of government. As all fingers point towards the federal government and how the federal authorities can lighten some of the load and relieve the taxpayers from incurring financial costs that should have been borne by the owners, it has neither been possible to undertake operations for removal nor possible to enforce preventative measures owing to the fact that the federal laws and system have proven to be somewhat less effective and efficient. As noted by MP Bernadette Jordan: “the responsibility for an abandoned vessel and derelict has been batted around for years … but now is the time for the federal government to step up and take a leadership role”. However, with the limited capacity and crucial gaps and drawbacks in the federal laws and the corresponding system, it might be quite challenging to live up to that commitment. Simply stated, the federal laws require a number of significant amendments, the commencing point being the implementation of a definition of “abandoned vessel and derelict” because the existing federal laws are devoid of a rationale “black-letter” explanation of what the term actually refers to.
Hydration Effects on the Permselectivity-Conductivity Trade-Off in Polymer Electrolytes

Polymer electrolytes, which are commonly used as separator materials in electrochemical devices, have ionic conductivity that is thought to be controlled by segmental mobility. Thus, any improvements made toward increasing ionic mobility come at the expense of mechanical integrity. However, selectively solvating the ionic domain, the region responsible for ion conduction, with water or polar organic solvents presents a potential opportunity to circumvent this physical constraint. Here, we explore the role of hydration on the transport properties of membranes formed from randomly sulfonated polystyrene (PS-r-sPS). We find that the water volume fraction underpins an intrinsic trade-off between separator permselectivity (Ψm) and ion conductivity (κ)—thus, improvements in ion diffusion because of increased water content come at the expense of charge density in the membrane which yields a reduced Ψm. We provide a summary of the Ψm–κ trade-off for a suite of commercially available separators to elucidate struct...
A long-acting 3TC ProTide nanoformulation suppresses HBV replication in humanized mice

Nowadays, there is a strong request for the treatment of chronic HBV-infection with direct acting antivirals. Furthermore, prevalent human immunodeficiency virus (HIV-1) and hepatitis B (HBV) co-infections highlight an immediate need for dual long-acting and easily administered antivirals. To this end, we modified lamivudine (3TC), a nucleoside analog inhibitor of both viruses, into a lipophilic monophosphorylated prodrug (M23TC). Prior work demonstrated that nanoformulation of M23TC (NM23TC) enhanced drug stability, controlled dissolution and improved access to sites of viral replication. The present study evaluated the efficacy of a NM23TC in HBV-infected chimeric liver humanized mice. Levels of HBV DNA and HBsAg in plasma were monitored up to 8 weeks posttreatment. A single intramuscular dose of 75 mg/kg 3TC equivalents of nanoformulated NM23TC provided sustained drug levels and suppressed HBV replication in humanized mice for 4 weeks. The results support further development of this long-acting 3TC nanoformulation for HBV treatment and prevention.
Temozolomide antagonizes oncolytic immunovirotherapy in glioblastoma.

Background Temozolomide (TMZ) chemotherapy is a current standard of care for glioblastoma (GBM), however it has only extended overall survival by a few months. Because it also modulates the immune system, both beneficially and negatively, understanding how TMZ interacts with immunotherapeutics is important. Oncolytic herpes simplex virus (oHSV) is a new class of cancer therapeutic with both cytotoxic and immunostimulatory activities. Here, we examine the combination of TMZ and an oHSV encoding murine interleukin 12, G47Δ-mIL12, in a mouse immunocompetent GBM model generated from non-immunogenic 005 GBM stem-like cells (GSCs. Methods We first investigated the cytotoxic effects of TMZ and/or G47Δ-IL12 treatments in vitro, and then the antitumor effects of combination therapy in vivo in orthotopically implanted 005 GSC-derived brain tumors. To improve TMZ sensitivity, O6-methylguanine DNA methyltransferase (MGMT) was inhibited. The effects of TMZ on immune cells were evaluated by flow cytometery and immunohistochemistry. Results The combination of TMZ+G47Δ-IL12 kills 005 GSCs in vitro better than single treatments. However, TMZ does not improve the survival of orthotopic tumor-bearing mice treated with G47Δ-IL12, but rather can abrogate the beneficial effects of G47Δ-IL12 when the two are given concurrently. TMZ negatively affects intratumor T cells and macrophages and splenocytes. Addition of MGMT inhibitor O6-benzylguanine (O6-BG), an inactivating pseudosubstrate of MGMT, to TMZ improved survival, but the combination with G47Δ-IL12 did not overcome the antagonistic effects of TMZ treatment on oHSV therapy. Conclusions These results illustrate that chemotherapy can adversely affect oHSV immunovirotherapy. As TMZ is the standard of care for GBM, the timing of these combined therapies should be taken into consideration when planning oHSV clinical trials with chemotherapy for GBM.
Is Office Laryngoscopy an Aerosol-Generating Procedure?

Objectives/hypothesis The aims of this work were 1) to investigate whether office laryngoscopy is an aerosol-generating procedure with an optical particle sizer (OPS) during clinical simulation on healthy volunteers, and 2) to critically discuss methods for assessment of aerosolizing potentials in invasive interventions. Study design Prospective quantification of aerosol and droplet generation during clinical simulation of rigid and flexible laryngoscopy. Methods Two healthy volunteers were recruited to undergo both flexible and rigid laryngoscopy. An OPS was used to quantify aerosols and droplets generated for four positive controls relative to ambient particles (speech, breathing, /e/ phonation, and /ae/ phonation) and for five test interventions relative to breathing and phonation (flexible laryngoscopy, flexible laryngoscopy with humming, flexible laryngoscopy with /e/ phonation, rigid laryngoscopy, and rigid laryngoscopy with /ae/ phonation). Particle counts in mean diameter size range from 0.3 to >10 μm were measured with OPS placed at 12 cm from the subject's nose/mouth. Results None of the laryngoscopy interventions (n = 10 each) generated aerosols above that produced by breathing or phonation. Breathing (n = 40, 1-3 μm, P = .016) and /ae/ phonation (n = 10, 1-3 μm, P = .022; 3-5 μm. P = .083; >5 μm, P = .012) were statistically significant producers of aerosols and droplets. Neither speech nor /e/ phonation (n = 10 each) were associated with statistically significant aerosols and droplet generation. Conclusions Using OPS to detect droplets and aerosols, we found that office laryngoscopy is likely not an aerosol-generating procedure. Despite its prior use in otolaryngological literature, an OPS has intrinsic limitations. Our study should be complemented with more sophisticated methods of droplet distribution measurement. Level of evidence 3 Laryngoscope, 130:2637-2642, 2020.
Wnt-induced, TRP53-mediated Cell Cycle Arrest of Precursors Underlies Interstitial Cell of Cajal Depletion During Aging.

Background & Aims Gastric dysfunction in the elderly may cause reduced food intake, frailty, and increased mortality. The pacemaker and neuromodulator cells interstitial cells of Cajal (ICC) decline with age in humans, and their loss contributes to gastric dysfunction in progeric klotho mice hypomorphic for the anti-aging Klotho protein. The mechanisms of ICC depletion remain unclear. Klotho attenuates Wnt (wingless-type MMTV integration site) signaling. Here, we examined whether unopposed Wnt signaling could underlie aging-associated ICC loss by up-regulating transformation related protein TRP53 in ICC stem cells (ICC-SC). Methods Mice aged 1–107 weeks, klotho mice, APCΔ468 mice with overactive Wnt signaling, mouse ICC-SC, and human gastric smooth muscles were studied by RNA sequencing, reverse transcription–polymerase chain reaction, immunoblots, immunofluorescence, histochemistry, flow cytometry, and methyltetrazolium, ethynyl/bromodeoxyuridine incorporation, and ex-vivo gastric compliance assays. Cells were manipulated pharmacologically and by gene overexpression and RNA interference. Results The klotho and aged mice showed similar ICC loss and impaired gastric compliance. ICC-SC decline preceded ICC depletion. Canonical Wnt signaling and TRP53 increased in gastric muscles of klotho and aged mice and middle-aged humans. Overstimulated canonical Wnt signaling increased DNA damage response and TRP53 and reduced ICC-SC self-renewal and gastric ICC. TRP53 induction persistently inhibited G1/S and G2/M cell cycle phase transitions without activating apoptosis, autophagy, cellular quiescence, or canonical markers/mediators of senescence. G1/S block reflected increased cyclin-dependent kinase inhibitor 1B and reduced cyclin D1 from reduced extracellular signal-regulated kinase activity. Conclusions Increased Wnt signaling causes age-related ICC loss by up-regulating TRP53, which induces persistent ICC-SC cell cycle arrest without up-regulating canonical senescence markers.
Fault Propagation, EMI Propagation, and Fault Containment in Aerospace Systems

The occurrence of faults in aerospace system hardware and software have consequences ranging from minor effects to catastrophic effects, and such faults can directly affect the safety of hardware and personnel. There are many origins to fault conditions, and the hardware that is capable of still meeting its performance requirements after experiencing itself a fault is said to be fault tolerant. A fault tolerant hardware is capable of detecting, isolating, and recovering from a fault condition; and this is a subfield of control engineering. An aerospace system that has been shown to have electromagnetic compatibility (EMC) in all its subsystems and systems cannot induced faults caused by electromagnetic interference (EMI). It can be proposed that the presence of EMI (or lack of EMC) is analogous to a potential fault initiator and the effects can likewise range from minor to severe. This paper starts by addressing the consequences of hardware failure in aerospace systems from a fault perspective, because the design of fault tolerant system is a major endeavor in aerospace. To arrive to this goal the paper starts with the concepts of fault, fault propagation, and a new concept called fault containment region. The paper then proceeds to provide two very recent examples in the aircraft industry of fault propagation with catastrophic effects. The paper proceeds to introduce the concept of EMI fault containment and a brief introduction to another new concept called the EMI containment region. The paper proceeds with an example of EMI fault containment region. The paper ends with a lesson learned conclusions.
Prognostic Factors of PTLD after SOT

Similar to other B-cell malignancies, the prognosis of post-transplant lymphoproliferative disorders (PTLD) subsequent to solid organ transplantation follows comparable principles. Despite remaining one of the most reliable prognostic systems, the International Prognostic Index does not fully hit the mark in regard to the complexity of PTLD and new proposed prognostic factors. Age, performance status, disease stage, and elevated LDH continue to be apropos prognostic factors in PTLD. The heterogeneous nature of PTLD and isolated single-center analyses make validation of updated risk factors difficult to ascertain. Biologic markers will undoubtedly become a backbone of prognostication once validated models become available. While wrought with limitations, when viewed as a conglomerate, certain patterns help provide clinical insight and guidance for practitioners treating PTLD. It is evident additional research in this serious complication of solid organ transplantation will be paramount to identifying future markers to help clinicians better prognosticate PTLD.
Sizing Extracellular Vesicles Using Membrane Dyes and a Single Molecule-Sensitive Flow Analyzer

Extracellular vesicles (EVs) are membranous particles released by most cells in our body, which are involved in many cell-to-cell signaling processes. Given the nanometer sizes and heterogeneity of EVs, highly sensitive methods with single-molecule resolution are fundamental to investigating their biophysical properties. Here, we demonstrate the sizing of EVs using a fluorescence-based flow analyzer with single-molecule sensitivity. Using a dye that selectively partitions into the vesicle's membrane, we show that the fluorescence intensity of a vesicle is proportional to its diameter. We discuss the constraints in sample preparation which are inherent to sizing nanoscale vesicles with a fluorescent membrane dye and propose several guidelines to improve data consistency. After optimizing staining conditions, we were able to measure the size of vesicles in the range ∼35-300 nm, covering the spectrum of EV sizes. Lastly, we developed a method to correct the signal intensity from each vesicle based on its traveling speed inside the microfluidic channel, by operating at a high sampling rate (10 kHz) and measuring the time required for the particle to cross the laser beam. Using this correction, we obtained a threefold greater accuracy in EV sizing, with a precision of ±15-25%.
Unifying Concepts in Electro- and Thermocatalysis toward Hydrogen Peroxide Production.

We examine relationships between H2O2 and H2O formation on metal nanoparticles by the electrochemical oxygen reduction reaction (ORR) and the thermochemical direct synthesis of H2O2. The similar mechanisms of such reactions suggest that these catalysts should exhibit similar reaction rates and selectivities at equivalent electrochemical potentials (μi), determined by reactant activities, electrode potential, and temperature. We quantitatively compare the kinetic parameters for 12 nanoparticle catalysts obtained in a thermocatalytic fixed-bed reactor and a ring-disk electrode cell. Koutecky-Levich and Butler-Volmer analyses yield electrochemical rate constants and transfer coefficients, which informed mixed-potential models that treat each nanoparticle as a short-circuited electrochemical cell. These models require that the hydrogen oxidation reaction (HOR) and ORR occur at equal rates to conserve the charge on nanoparticles. These kinetic relationships predict that nanoparticle catalysts operate at potentials that depend on reactant activities (H2, O2), H2O2 selectivity, and rate constants for the HOR and ORR, as confirmed by measurements of the operating potential during the direct synthesis of H2O2. The selectivities and rates of H2O2 formation during thermocatalysis and electrocatalysis correlate across all catalysts when operating at equivalent μi values. This analysis provides quantitative relationships that guide the optimization of H2O2 formation rates and selectivities. Catalysts achieve the greatest H2O2 selectivities when they operate at high H atom coverages, low temperatures, and potentials that maximize electron transfer toward stable OOH* and H2O2* while preventing excessive occupation of O-O antibonding states that lead to H2O formation. These findings guide the design and operation of catalysts that maximize H2O2 formation, and these concepts may inform other liquid-phase chemistries.
Integrating big data and cloud computing topics into the computing curricula: A modular approach

Abstract Big data and cloud computing collectively offer a paradigm shift in the way businesses are now acquiring, using, and managing information technology. This creates the need for every CS student to be equipped with foundational knowledge in this collective paradigm and possess some hands-on experience in deploying and managing big data applications in the cloud. This study argues that, for substantial coverage of big data and cloud computing concepts and skills, the relevant topics need to be integrated into multiple core courses across the CS curriculum rather than creating additional courses and performing a major overhaul of the curriculum. Our approach to including these topics is to develop autonomous competency-based learning modules for specific core courses in which their coverage might find an appropriate context. In this paper, four such modules are discussed, and our classroom experiences during these interventions are documented. Student performance data and survey results show reasonable success in attaining student learning outcomes, enhanced engagement, and interests.
Numerical error analysis for an energy-stable HDG method for the Allen–Cahn equation

Abstract This paper presents an energy-stable hybridizable interior penalty discontinuous Galerkin method for the Allen–Cahn equation. To obtain an unconditionally energy stable scheme, the energy potential is split into a sum of a convex and concave function. Energy stability for the proposed scheme is proven to hold for arbitrary time. Existence and uniqueness for the scheme is also established. Under standard assumptions on the energy potential (Lipschitz continuity), we demonstrate rigorously that the method converges optimally for symmetric schemes, and suboptimally for nonsymmetric schemes. Several examples are provided which numerically verify and validate the method.
Development of infants’ neural speech processing and its relation to later language skills: an MEG study

The 9sensitive period9 for phonetic learning (~6-12 months) is one of the earliest milestones in language acquisition where infants start to become specialized in processing speech sounds in their native language. In the last decade, advancements in neuroimaging technologies for infants are starting to shed light on the underlying neural mechanisms supporting this important learning period. The current study reports on the largest longitudinal dataset to date with the aim to replicate and extend on two important questions: 1) what are the developmental changes during the 9sensitive period9 for native and nonnative speech processing? 2) how does native and nonnative speech processing in infants predict later language outcomes? Fifty-four infants were recruited at 7 months of age and their neural processing of speech was measured using Magnetoencephalography (MEG). Specifically, the neural sensitivity to a native and a nonnative speech contrast was indexed by the mismatch response (MMR). They repeated the measurement again at 11 months of age and their language development was further tracked from 12 months to 30 months of age using the MacArthur-Bates Communicative Development Inventory (CDI). Using an a prior Region-of-Interest (ROI) approach, we observed significant increases for the Native MMR in the left inferior frontal region (IF) and superior temporal region (ST) from 7 to 11 months, but not for the Nonnative MMR. Complementary whole brain comparison revealed more widespread developmental changes for both contrasts. However, only individual differences in the left IF and ST for the Nonnative MMR at 11 months of age were significant predictors of individual vocabulary growth up to 30 months of age. An exploratory machine-learning based analysis further revealed that whole brain MMR for both Native and Nonnative contrasts can robustly predict later outcomes, but with very different underlying spatial-temporal patterns. The current study extends our current knowledge and suggests that native and nonnative speech processing may follow different developmental trajectories and utilize different mechanisms that are relevant for later language skills.
Fractal Concepts and the Analysis of Atmospheric Inhomogeneities

The concepts of fractal and fractal dimension are reviewed in the context of atmospheric turbulent diffusion processes. Examples from the literature show how fractal dimension serves as a measure of the degree to which the turbulent cascade is space-filling and how this relates to the classical Kolmogorov description. A qualitative description of shear-layer turbulence is used to illustrate some of the concepts. Finally, two methods for calculating fractal dimension are described, along with ways in which these methods might be applied to lidar observations of smoke plume cross sections.
Analysis of distributed thermopiezoelectric sensors and actuators inadvanced intelligent structures

The quasistatic equations of piezoelectricity and thermopiezoelectricity are used to develop a finite element formulation of distributed piezoelectric and thermopiezoelectric media. The formulation is then integrated with the distributed sensing and control of advanced intelligent structure design. The procedure is illustrated with the help of two example problems. The purpose of the first example, which consists of two piezoelectric layers used as a bimorph robotic finger, is to check the accuracy of the finite element solution with the analytical one. As a second example, an aluminum beam is utilized along with two polyvinylidene fluoride layers acting as distributed actuator and sensor to study the distributed control of the beam when thermal effects are present. It is concluded that the thermal effects are important in the precision distributed control of intelligent structures.
Case studies using graphically enhanced computer software to improve technology assessments and enhance clinical decisions

This paper describes how clinical engineers and healthcare CIOs, CTOs, and IT/IS specialists can use the Analytic Hierarchy Process (AHP) to improve the quality of diverse and important decisions that hospitals face today. AHP is a versatile and proven decision support tool that allows the user to design a hierarchical structure for decision-making and weighs the trade-offs between decision criteria and alternatives (Saaty 1977, Saaty 1996).
Supercontinuum Generation in Condensed Matter

Supercontinuum generation, the production of intense ultrafast broadband "white light" pulses, arises from the propagation of intense picosecond or shorter laser pulses through condensed or gaseous media. Various processes are responsible for continuum generation. These are called self-, induced-, and cross-phase modulations and four-photon parametric generation. Whenever an intense laser pulse propagates through a medium, it changes the refractive index, which in turn changes the phase, amplitude, and frequency of the incident laser pulse. A phase change can cause a frequency sweep within the pulse envelope. This process has been called self-phase modulation (SPM) (Alfano and Shapiro, 1970a). Nondegenerate four-photon parametric generation (FPPG) usually occurs simultaneously with the SPM process (Alfano and Shapiro, 1970a). Photons at the laser frequency parametrically generate photons to be emitted at Stokes and anti-Stokes frequencies in an angular pattern due to the required phase-matching condition. When a coherent vibrational mode is excited by a laser, stimulated Raman scattering (SRS) occurs. SRS is an important process that competes and couples with SPM. The interference between SRS and SPM causes a change in the emission spectrum resulting in stimulated Raman scattering cross-phase modulation (SRS-XPM) (Gersten et al., 1980). A process similar to SRS-XPM occurs when an intense laser pulse propagates through a medium possessing a large second-order χ2 and third-order χ 3 susceptibility. Both second harmonic generation (SHG) and SPM occur and can be coupled together. The interference between SHG and SPM alters the emission spectrum and is called second harmonic generation cross-phase modulation (SHG-XPM) (Alfano et al., 1987). A process closely related to XPM, called induced phase modulation (IPM) (Alfano, 1986), occurs when a weak pulse at a different frequency propagates through a disrupted medium whose index of refraction is changed by an intense laser pulse. The phase of the weak optical field can be modulated by the time variation of the index of refraction originating from the primary intense pulse.
DESIGNING FOR SITUATION AWARENESS AND TRUST IN AUTOMATION

Abstract In this paper, we synthesize data from the laboratory, from pilot surveys and from accident and incident analysis, to identify five problem areas in flight deck automation, related to overtrust (complacency), mistrust, workload, situation awareness and perceived control. Causes of these problems are identified, and four categories of solutions are proposed in seeking the goal of pilot-centered automation: these solutions relate to simplification, display design, training, and corporate policy.
Archaeology, Politics of

Most people do not think of archaeology as political, but issues focused on the repatriation of human remains and sacred objects have made archaeology a very political discipline. Repatriation of human remains and sacred objects has become a focus of concern in the United States, Canada, Australia, and other countries over the last 20 years. This article examines the definitions and nature of repatriation, the history of repatriation laws and approaches, the politics of the issues, international vs US laws, key issues and foci of current debate, and potential future issues associated with repatriation. There has been a marked culture change among archaeologists and museums concerning these issues, and this shift will have a lasting impact on archaeology, on indigenous peoples, and on the nature of museums. Archaeology can no longer claim to exist outside politics.
The Sensory Control of the White Rat in the Maze Habit

*Received for publication by Walter S. Hunter of the Editorial Board, August 17, 1928. 1Received for publication by Walter S. Hunter of the Editorial Board, August 17, 1928.
Data Salmon: a greedy mobile basestation protocol for efficient data collection in wireless sensor networks

Our work addresses the spatiotemporally varying nature of data traffic in environmental monitoring and surveillance applications. By employing a network-controlled mobile basestation (MB), we present a simple energy-efficient data collection protocol for wireless sensor networks (WSNs). In contrast to the existing MB-based solutions where WSN nodes buffer data passively until visited by an MB, our protocol maintains an always-on multihop connectivity to the MB by means of an efficient distributed tracking mechanism. This allows the nodes to forward their data in a timely fashion, avoiding latencies due to long-term buffering. Our protocol progressively relocates the MB closer to the regions that produce higher data rates and reduces the average weighted multihop traffic, enabling energy savings. Using the convexity of the cost function, we prove that our local and greedy protocol is in fact optimal.
Elementary Theory of Holomorphic Functions

In this chapter, we shall develop the classical theory of holomorphic functions. The Looman—Menchoff theorem, proved in §1.6, is less standard than the rest of the material.