cssi/SciSciGPT-SciSciNet huggingface dataset:
In Vitro and In Vivo Characterization of Full-Length rFVIII Modified with PEG Via Coupling to Primary Amino Groups.

Chemical modification of recombinant therapeutic proteins with PEG has been shown to enhance the biological half-life. Here we assess the effect of PEGylation on FVIII. Full-length rFVIII bulk drug substance from protein-free fermentation (Advate process, Baxter) was conditioned into a buffer suitable for coupling to polyethylene glycol succinimidyl succinate (linear PEG, 5 kDa PEG chain length). PEG was covalently bound by amine coupling preferentially to lysine residues of FVIII at neutral pH. PEG was removed by ion-exchange chromatography and the PEG-FVIII derivative was concentrated by ultra-diafiltration. The conjugates thus obtained retained about 30–40% of the activity of non-modified rFVIII. The specific activity decreased with the amount of PEG linked to the FVIII molecule. In SDS-PAGE and immunoblot studies PEGylated rFVIII showed a band pattern similar to unmodified FVIII with full-length, heavy chain fragments of 180 kDa and 120 kDa and the light chain fragment of 80 kDa. PEGylation also occurred to a high extent in the B domain of FVIII. All bands appeared broadened due to the attachment of polymeric PEG. The maintenance of functionality of FVIII was demonstrated by its potential to be activated and inactivated by thrombin. In the assay PEGylated and unmodified FVIII were incubated with 1 nM thrombin. Sub-samples were drawn at intervals up to 40 minutes and added to a mixture of FIXa, FX, phospholipid vesicles and Ca 2+ containing a thrombin inhibitor. After 3 minutes incubation at 37°C the amount of activated FX (FXa) was measured using a FXa-specific chromogenic substrate. Unmodified rFVIII showed a typical picture of an immediate increase in FXa activity and a subsequent decline with no further FXa generation after 15 minutes. PEGylated rFVIII was activated to the same extent as unmodified FVIII but the decay in FXa generation was slower and did not reach the zero level, even 40 minutes after incubation. The formation of the typical thrombin cleavage fragments, with unmodified as well as PEGylated rFVIII, was demonstrated in a Western blot analysis. The slower inactivation by thrombin was also seen there. The pharmacokinetic properties of PEGylated rFVIII compared with rFVIII were investigated in hemophilia A knock-out mice. Both preparations were applied at a dose of 200 IU rFVIII/kg and groups of mice (n=5) were exsanguinated at several time points up to 24 hours. Terminal half-life for PEGylated rFVIII was calculated at 4.9 hours compared with 1.9 hours for unmodified rFVIII in hemophilia A knock-out mice. AUC was approximately doubled. These results indicate that rFVIII can be biochemically modified with PEG whilst at least partly retaining its major functions, but at the same time prolonging its survival in the circulation of hemophilic mice.
Types of Male Sterility

In view of the definition of male sterility given earlier, a tentative scheme of classifying different types of naturally occurring malesteriles may be based primarily on two criteria, namely the phenotypic identity and the cause of incidence.
Association between mortality and replacement solution bicarbonate concentration in continuous renal replacement therapy: A propensity-matched cohort study.

Background Given the known deleterious effects seen with bicarbonate supplementation for acidemia, we hypothesized that utilizing high bicarbonate concentration replacement solution in continuous venovenous hemofiltration (CVVH) would be independently associated with higher mortality. Methods In a propensity score-matched historical cohort study conducted at a single tertiary care center from December 9, 2006, through December 31, 2009, a total of 287consecutive adult critically ill patients with Stage III acute kidney injury (AKI) requiring CVVH were enrolled. We excluded patients on maintenance dialysis, those who received other modalities of continuous renal replacement therapies, and patients that received a mixed of 22 and 32 mEq/L bicarbonate solution pre- and post-filter. The primary outcome was in-hospital and 90-day mortality rates. Results Among enrollees, 68 were used 32 mEq/L bicarbonate solution, and 219 received 22mEq/L bicarbonate solution for CVVH. Patients on 32 mEq/L bicarbonate solution were more often non-surgical, had lower pH and bicarbonate level but had higher blood potassium and phosphorus levels in comparison with those on 22 mEq/L bicarbonate solution. After adjustment for the baseline characteristics, the use of 32 bicarbonate solution was significantly associated with increased in-hospital (HR = 1.94; 95% CI 1.02–3.79) and 90-day mortality (HR = 1.50; 95% CI 1.03–2.14). There was a significant increase in the hospital (p = .03) and 90-day (p = .04) mortality between the 22 vs. 32 mEq/L bicarbonate solution groups following propensity matching. Conclusion Our data showed there is a strong association between using high bicarbonate solution and mortality independent of severity of illness and comorbid conditions. These findings need to be evaluated further in prospective studies.
Advances in Computational Simulation of Gravity-Induced Disproportionate Collapse of RC Frame Buildings

Abstract Current methods and practices for modeling and numerical simulation of disproportionate collapse of reinforced concrete (RC) frame buildings are reviewed. Modeling advances at the componen...
Evaluating medicinal plants for anticancer properties: testing plant extracts for cytotoxicity

Cancer describes a category of diseases which involve the uncontrolled growth of abnormal cells and the spread or metastasis of those cells to other sites in the body. Natural products derived from plants have been shown to be valuable sources for anticancer drug discovery. The long term goal of this project is to isolate potential anticancer compounds from medicinal plants through bioassay guided fractionation. Towards this purpose, we commenced our research by performing cytotoxicity assays on chemical extracts obtained from plants with medicinal properties or health benefits. The plants included in this study are commonly known as muscadine, scarlet bush, Brazilian pepper, anamu, moringa, guanabana, oyster plant, and Okinawa spinach. Plant extracts, prepared with aqueous and/or organic solvents (including dimethyl sulfoxide, ethanol and hexane), were tested on MCF-7 breast cancer cells cultured in vitro. Methylthiazol tetrazolium (MTT) assays were used to quantify cytotoxicity. Preliminary data indicated the extracts were not cytotoxic at the concentrations tested. Indeed, extracts from each type of plant improved cell viability. These data provide valuable dosing information regarding extract concentrations for upcoming experiments. In the future, extracts will be tested on other human cancer cell lines, as well as in cell-invasion assays, which model metastatic processes.
Hospital variation in mortality after emergent bowel resections: The role of failure-to-rescue

Background Hospital variation in failure-to-rescue (FTR) rates has partially explained nationwide differences in mortality after elective surgeries. To examine the role of FTR among emergency general surgery, we compared nationwide risk-adjusted mortality, complications, and FTR rates after emergent bowel resections. Methods We identified patients who underwent emergent small or large bowel resections in the 2010 to 2011 Nationwide Inpatient Sample using the American Association for the Surgery of Trauma criteria. We then calculated risk-adjusted mortality rates for each hospital using multivariable logistic regressions and postestimation, which adjusted for patient age, sex, race and ethnicity, payer status, comorbidities, and hospital clustering. After excluding hospitals with fewer than 10 resections per year, we ranked the remaining hospitals by their risk-adjusted mortality rates and divided them into five quintiles. We compared both risk-adjusted complication rates and FTR rates between the top (lowest mortality) and bottom (highest mortality) quintiles. Results We identified 21,564 emergent bowel resections, weighted to 105,925 procedures nationwide. The bottom quintile of hospitals had an overall risk-adjusted mortality rate that was 10.9 times higher than that of the top quintile of hospitals (15.3% vs. 1.4%). While risk-adjusted complication rates were similarly high for both the bottom and the top quintiles of hospitals (22.5% vs. 15.7%), the risk-adjusted FTR rates were 10.8 times higher in the bottom quintile of hospitals relative to the top quintile of hospitals (33.4% vs. 3.1%). Using larger hospital volume thresholds yielded similar findings. Furthermore, large variations existed in complication-specific FTR rates (surgical site infection [6.6%] to myocardial infarction [29.4%]). Conclusion Nationwide hospital variation in risk-adjusted mortality rates exist after emergent bowel resections. As complication rates were similar across hospitals, the significantly higher FTR rates at higher-mortality hospitals may drive this variation in mortality. System-level initiatives addressing the management of postoperative complications may improve patient care and reduce variation in outcomes. Level of evidence Prognostic and epidemiological study, level IV.
From imperial pyramids to anticolonial sundials: commemorating and contesting French geodesy in Ecuador

Abstract This article considers the marking of the Andean equatorial zone through the construction, destruction and reconstruction of pyramids and obelisks celebrating the eighteenth-century Franco-Hispanic geodesic mission to Quito. These structures, originally constructed by that mission and lauding Enlightenment rationality and European empire, have been redefined in the twentieth and twenty-first centuries as icons of Ecuadorian nationalism, within both a Eurocentric memorial and an Andean counter-memorial tradition. The article traces these traditions, from medieval orientalist fascination with ancient Egypt to contemporary disputes regarding pre-Columbian indigenous astronomy. As the geodesic pyramidal marker became a contested site of local and national identity, their location also shifted, from the points of geodesic measurements to the more visible and tourist friendly equator. Key players in this history include French academicians and military scientists, Ecuadorian radical liberal politicians, highland indigenous communities, tourist boosters and amateur equator aficionados.
Theoretical prediction and atomic kinetic Monte Carlo simulations of void superlattice self-organization under irradiation

Nano-structured superlattices may have novel physical properties and irradiation is a powerful mean to drive their self-organization. However, the formation mechanism of superlattice under irradiation is still open for debate. Here we use atomic kinetic Monte Carlo simulations in conjunction with a theoretical analysis to understand and predict the self-organization of nano-void superlattices under irradiation, which have been observed in various types of materials for more than 40 years but yet to be well understood. The superlattice is found to be a result of spontaneous precipitation of voids from the matrix, a process similar to phase separation in regular solid solution, with the symmetry dictated by anisotropic materials properties such as one-dimensional interstitial atom diffusion. This discovery challenges the widely accepted empirical rule of the coherency between the superlattice and host matrix crystal lattice. The atomic scale perspective has enabled a new theoretical analysis to successfully predict the superlattice parameters, which are in good agreement with independent experiments. The theory developed in this work can provide guidelines for designing target experiments to tailor desired microstructure under irradiation. It may also be generalized for situations beyond irradiation, such as spontaneous phase separation with reaction.
Vitamin A and the nursing mother-infant dyad: evidence for intervention.

The role of vitamin A in improving child health and survival in vitamin A deficient regions of the works was firmly established in the early 1990’s, after a series of randomized trials showed that vitamin A supplementation decreased mortality in children 6 months to 5 years of age by around 24%.1 However the importance of vitamin A to health outcomes in women of reproductive age and infants 0–6 months of age remains a topic of debate and area of active research. The prupose of this to highlight the important questions from a public health perspective, and to discuss the latest ideas and research results related to health outcomes in lactating women an their young infants. In the process, we will make the the argument that while our understandings remain imperfect, the evidence at hand is sufficient to justify more aggressive interventions to improve the vitamin A status of prefnant and lactating mothers and young infants.
CHROMOGENIC ACID-LABILE PROTECTING GROUPS FOR USE IN PEPTIDE SYNTHESIS

Publisher Summary This chapter discusses the chromogenic acid-labile protecting groups for use in peptide synthesis. In the trityl butyl groups, the formation of the carbonium ion is assisted by conjugative electron displacement and, once formed, the carbonium ion is stabilized by conjugative mesomerism. The formation of the tertiary butyl carbonium ion is assisted by the inductive effect of the methyl groups, and the resultant ion is stabilized, to some extent, by hyperconjugative mesomerism. The relationship between the degree of heterolysis and the structure of the alkyl or aralkyl group is similar, allowing for differences in protonation. 4,4'-dimethoxy-benzhydryl; 3,3',4,4'-tetramethoxy-benzhydryl; and 2,2'-dimethyl-4,4'-dimethoxy-benzhydryl chlorides react readily with amino-acid esters in chloroform solution in the presence of triethylamine to yield the corresponding N-substituted amino-acid methyl esters. In a manner reminiscent of the trityl amino-acid series, benzhydryl-glycine methyl ester derivatives are readily saponified whereas the phenylalanine compounds show marked resistance to saponification. Saponification is slightly less hindered in the benzhydryl than in the trityl series.
Osthoff, Hermann (1847–1909)

Hermann Osthoff (b. 1847) studied Germanic philology, Sanskrit, and comparative grammar. He belonged to the Neogrammarian movement, but was nevertheless a scholar who soon came to establish his own scientific agenda. He contributed substantially to drawing practical conclusions from the theoretical teachings of the Neogrammarians by exploring in greater detail the development of the sounds and the grammatical forms in the older stages of the IE languages. His specialty, aside from the Germanic languages, included Classical Greek and Latin as well as the Old Indic languages.
Pyrosequence-based typing of alleles of the HLA-DQB1 gene.

DNA typing of alleles of the highly polymorphic HLA-DQB1 gene was performed by Pyrosequencing™ using purified DNA from the 11th International Histocompatibility Workshop human cell lines and samples from the Children’s Hospital of Pittsburgh registry of diabetics and their first-degree relatives. Pyrosequencing was optimized for genotyping exon 2 of the HLA-DQB1 gene, but the procedure should be applicable to other HLA loci. The 47 HLA-DQB1 alleles were readily identifiable, as were the 1128 potential allelic heterozygous combinations. The method required PCR conditions that specifically amplified DQB1 but not the pseudogene, DQB2. The new method of pyrosequence-based typing can be performed in 96- or 384-well format. The 61 polymorphic residues of DQB1 exon 2 were identified within four pyrosequencing reactions, obtained by a 70-nucleotide read length in each reaction, in about an hour’s time. Allelic combinations of HLA-DQB1 most frequently found in the population of diabetics and their immediate family...
Faith, Squirrels, and Artwork: The Expansive Agency of Textual Coordination in the Literate Action of Older Writers

Agency is a central concern of gerontology, age studies, and life course research, but the role of literate action in supporting and perpetuating agency in older adult writers is not well understood. A conceptual framework for the relationship between agency and literate action would provide important insight into contemporary writing research on older writers. In this study, I trace the literate practices of one writer, Frank, in order to understand how he used literate action to both negotiate his lifeworlds and support his own agency in his life after his retirement from an engineering career. Drawing on posthumanist understandings of agency, I use a combination of sociohistoric (Erickson and Roozen) and sociological (Brandt) methodologies to trace Frank’s literacy history, the chronotopes for writing that he enacts, and the agency that he develops and supports through that chronotopic work. I focus in particular on the acts of textual coordination that Frank enacts, using those data points to understand how Frank creates objects in his daily writing that bolster his agency in future social situations—a concept I refer to as expansive agency .
Performance comparisons of a PV system by monitoring Solar irradiance with different pyranometers

The use of the term "availability" to describe a photovoltaic (PV) system and power plant has been fraught with confusion for many years. A term that is meant to describe equipment operational status is often omitted, misapplied or inaccurately combined with PV performance metrics due to attempts to measure performance and reliability through the lens of traditional power plant language. This paper discusses three areas where current research in standards, contract language and performance modeling is improving the way availability is used with regards to photovoltaic systems and power plants.
Treatment failure of syringomyelia associated with Chiari I malformation following foramen magnum decompression: how should we proceed?

The preferred treatment of patients with persistent, recurrent, or progressive syringomyelia after foramen magnum decompression (FMD) for Chiari I (CMI)-associated syringomyelia is controversial, and may include redo FMD, stabilization, or shunting procedures (such as syringopleural or syringo-subarachnoid shunts). We describe our experience in treating these patients and discuss the treatment modalities for these patients. We retrospectively collected data of CMI patients with persistent, recurrent, or progressive syringomyelia after FMD. In addition to baseline characteristics, surgical treatments and neurological and radiological outcomes were assessed. Further, we assessed through uni- and multivariate analyses possible technical, surgical, and radiological factors which might lead to failed FMD. Between 1998 and 2017, 48 consecutive patients (35 females (73%), average age 16.8 ± 11.5 years) underwent FMD for a syringomyelia-Chiari complex. Twenty-four patients (50%) underwent surgical treatment for a persistent (n = 10), progressive (n = 12), or recurrent (n = 2) syringomyelia 21.4 ± 27.9 months (median 14.6 months, range 12 days–134.9 months) after FMD. Of all analyzed factors, only extradural FMD was significantly associated with lower failure rates. Two patients (8%) underwent redo FMD, 18 (75%) underwent 19 syringo-subarachnoid-shunts, and 4 (17%) had 6 cranial CSF diversion procedures. The overall follow-up time was 40.1 ± 47.4 months (median 25 months, range 3–230 months). Based on our results, 50% of the patients undergoing FMD for syringomyelia-Chiari complex may require further surgical treatment due to persistent, progressive, or recurrent syringomyelia. Treatment should be tailored to the suspected underlying pathology. A subgroup of patients may be managed conservatively; however, these patients need close clinical and radiological follow-ups. The technical aspects of FMD in CMI-syrinx complex should be the focus of larger studies, as an effort to improve failure rates.
High-throughput, label-free, single-cell photoacoustic microscopy of intratumoral metabolic heterogeneity

Intratumoral heterogeneity, which is manifested in almost all of the hallmarks of cancer, including the significantly altered metabolic profiles of cancer cells, represents a challenge to effective cancer therapy. High-throughput measurements of the metabolism of individual cancer cells would allow direct visualization and quantification of intratumoral metabolic heterogeneity, yet the throughputs of current measurement techniques are limited to about 120 cells per hour. Here, we show that single-cell photoacoustic microscopy can reach throughputs of approximately 12,000 cells per hour by trapping single cells with blood in an oxygen-diffusion-limited high-density microwell array and by using photoacoustic imaging to measure the haemoglobin oxygen change (that is, the oxygen consumption rate) in the microwells. We demonstrate the capability of this label-free technique by performing high-throughput single-cell oxygen-consumption-rate measurements of cultured cells and by imaging intratumoral metabolic heterogeneity in specimens from patients with breast cancer. High-throughput single-cell photoacoustic microscopy of oxygen consumption rates should enable the faster characterization of intratumoral metabolic heterogeneity.
House price impacts of construction quality and level of maintenance on a regional housing market: Evidence from King County, Washington

Accurately estimating the monetary value of the construction quality and the level of maintenance of a house is a significant gap in house price research. Such estimates would be valuable for vario...
Investigation of the source-detector separation in near infrared spectroscopy for healthy and clinical applications

Understanding near infrared light propagation in tissue is vital for designing next generation optical brain imaging devices. Monte Carlo (MC) simulations provide a controlled mechanism to characterize and evaluate contributions of diverse near infrared spectroscopy (NIRS) sensor configurations and parameters. In this study, we developed a multilayer adult digital head model under both healthy and clinical settings and assessed light-tissue interaction through MC simulations in terms of partial differential pathlength, mean total optical pathlength, diffuse reflectance, detector light intensity and spatial sensitivity profile of optical measurements. The model incorporated four layers: scalp, skull, cerebrospinal-fluid and cerebral cortex with and without a customizable lesion for modeling hematoma of different sizes and depths. The effect of source-detector separation (SDS) on optical measurements' sensitivity to brain tissue was investigated. Results from 1330 separate simulations [(4 lesion volumes × 4 lesion depths for clinical +3 healthy settings) × 7 SDS × 10 simulation = 1330)] each with 100 million photons indicated that selection of SDS is critical to acquire optimal measurements from the brain and recommended SDS to be 25 to 35 mm depending on the wavelengths to obtain optical monitoring of the adult brain function. The findings here can guide the design of future NIRS probes for functional neuroimaging and clinical diagnostic systems.
Selecting between two transition states by which water oxidation intermediates decay on an oxide surface

Although catalytic mechanisms on electrode surfaces have been proposed for decades, the pathways by which the product’s chemical bonds evolve from the initial charge-trapping intermediates have not been resolved. Here, we discover a reactive intermediate population with states in the middle of a semiconductor’s bandgap that reveal the dynamics of two parallel transition state pathways for their decay. After phototriggering the water oxidation reaction from the n-SrTiO3 surface, the microsecond decay of the intermediates affirms transition state theory through two distinct time constants, the primary kinetic salt and H/D kinetic isotope effects, realistic activation barrier heights and transition state theory pre-factors. Furthermore, we show that the reaction conditions can be adjusted to allow selection between the two pathways, one characterized by a labile intermediate facing the electrolyte (the oxyl), and the other by a lattice oxygen (the bridge). In summary, we experimentally isolate an important activation barrier in multi-electron transfer water oxidation and, in doing so, identify competing mechanisms for O2 evolution at surfaces. Elucidating reaction mechanisms on electrode surfaces is of utmost importance. Now, using canonical transition state theory, Cuk and colleagues show the competing pathways by which the charge-trapping intermediates of the water oxidation reaction on n-SrTiO3 decay towards the next step in the reaction.
Determination of U-bolt connection load capacities in overhead sign support structures

Abstract The load capacities of the U-bolt connections used in steel overhead sign trusses for the Iowa Department of Transportation (DOT) are not known because the bolts are used in ways that do not match available manufacturer data. Although these U-bolt connections appear to have performed satisfactorily in the past, there has been a growing safety concern in recent years because of the need for overhead sign trusses to support larger signs with greater span lengths. The objective of this project is to develop effective and efficient methodologies to realistically estimate the capacity of the U-bolt connections specified in the actual Steel Overhead Sign Truss (SOST) design standards. To achieve this objective, a literature search on the utilization and modeling techniques for U-bolt connections was first conducted. Three laboratory tests were then performed on two types of specimens with loading directions of 0° and 90° for the Type-A specimen and 0° for the Type-B specimen. The data collected from the tests were used to calibrate finite element models (FEM). Finally, the calibrated models were then used in a parametric study to calculate the yield and ultimate capacity of both types of specimens with various material properties and load resultant directions.
Knockout of the circadian clock protein PER1 results in sex-dependent alterations of ET-1 production in mice in response to a high-salt diet plus mineralocorticoid treatment.

Previously, we showed that global knockout (KO) of the circadian clock transcription factor PER1 in male, but not female, mice fed a high-salt diet plus mineralocorticoid treatment (HS/DOCP) result...
Chromatin potential identified by shared single cell profiling of RNA and chromatin

Cell differentiation and function are regulated across multiple layers of gene regulation, including the modulation of gene expression by changes in chromatin accessibility. However, differentiation is an asynchronous process precluding a temporal understanding of the regulatory events leading to cell fate commitment. Here, we developed SHARE-seq, a highly scalable approach for measurement of chromatin accessibility and gene expression within the same single cell. Using 34,774 joint profiles from mouse skin, we develop a computational strategy to identify cis-regulatory interactions and define Domains of Regulatory Chromatin (DORCs), which significantly overlap with super-enhancers. We show that during lineage commitment, chromatin accessibility at DORCs precedes gene expression, suggesting changes in chromatin accessibility may prime cells for lineage commitment. We therefore develop a computational strategy (chromatin potential) to quantify chromatin lineage-priming and predict cell fate outcomes. Together, SHARE-seq provides an extensible platform to study regulatory circuitry across diverse cells within tissues.
Parametric g-formula implementations for causal survival analyses.

The g-formula can be used to estimate the survival curve under a sustained treatment strategy. Two available estimators of the g-formula are noniterative conditional expectation and iterative conditional expectation. We propose a version of the iterative conditional expectation estimator and describe its procedures for deterministic and random treatment strategies. Also, because little is known about the comparative performance of noniterative and iterative conditional expectation estimators, we explore their relative efficiency via simulation studies. Our simulations show that, in the absence of model misspecification and unmeasured confounding, our proposed iterative conditional expectation estimator and the noniterative conditional expectation estimator are similarly efficient, and that both are at least as efficient as the classical iterative conditional expectation estimator. We describe an application of both noniterative and iterative conditional expectation to answer "when to start" treatment questions using data from the HIV-CAUSAL Collaboration.
Trans-trigeminal transport of masseter-derived neprilysin to hippocampus

Abstract Objective To show the possible occurrence of exosomal transport of neprilysin from masseter muscle to hippocampus via trigeminal nerve in the living mouse. Design Mouse C2C12 myotube-derived exosomes were labeled with near-infrared (NIR) dye and injected into the masseter muscle to track their fluorescence from masseter muscle to hippocampus via trigeminal nerve. A plasmid vector encoding green fluorescent protein (GFP)-tagged neprilysin (GFP-neprilysin) was transfected into masseter muscle of C57BL/6 J mice. Expression of mRNA and encoded protein of the transgene was identified in masseter muscle, trigeminal nerve and hippocampus by RT-PCR and Western blot, respectively. Results Peak of exosomal NIR in masseter muscle at time 0 rapidly reduced at 3 h and 6 h along with the subsequent increases in trigeminal nerve and hippocampus. Expression of GFP-neprilysin mRNA was detected in masseter muscle, but not trigeminal nerve and hippocampus. On the other hand, the corresponding protein of GFP-neprilysin was identified in the three tissues on day 3 after transfection into masseter muscle as a single band on Western blots with anti-GFP and anti-neprilysin antibodies. Conclusion The appearance of GFP-neprilysin protein in trigeminal nerve and hippocampus without a corresponding mRNA expression indicated the protein’s origin from the masseter muscle. Concomitant migration of NIR-exosomes from masseter muscle to hippocampus via trigeminal nerve suggested the possible occurrence of exosomal transport of neprilysin.
A New Sustainability Model – A Four Essential Quadrants Framework

Research purpose. This paper will present contemporary ideas on how, when, and where the four quadrants are vital to the sustainability of an organization and central to the future of the entity. There have long been suppositions and actual operational level models featuring three primary rudiments. Much of the prior research and modeling has centered on Economic, Social, and Environmental as the basis for sustainability within business models. This particular research brought new perspectives and addressed some deficiencies in the existing sustainability models.
A novel function for Rab1 and Rab11 during secretory granule maturation

Regulated exocytosis is an essential process whereby specific cargo proteins are secreted in a stimulus-dependent manner. Cargo-containing secretory granules are synthesized in the trans-Golgi network (TGN); after budding from the TGN, granules undergo modifications, including an increase in size. These changes occur during a poorly understood process called secretory granule maturation. Here, we leverage the Drosophila larval salivary glands as a model to characterize a novel role for Rab GTPases during granule maturation. We find that secretory granules increase in size ∼300-fold between biogenesis and release, and loss of Rab1 or Rab11 reduces granule size. Surprisingly, we find that Rab1 and Rab11 localize to secretory granule membranes. Rab11 associates with granule membranes throughout maturation, and Rab11 recruits Rab1. In turn, Rab1 associates specifically with immature granules and drives granule growth. In addition to roles in granule growth, both Rab1 and Rab11 appear to have additional functions during exocytosis; Rab11 function is necessary for exocytosis, while the presence of Rab1 on immature granules may prevent precocious exocytosis. Overall, these results highlight a new role for Rab GTPases in secretory granule maturation.
Characterizing learner behavior from touchscreen data

Abstract As educational approaches increasingly adopt digital formats, data logs create a newfound wealth of information about student behaviors in those learning environments for educators and researchers. Yet making sense of that information, particularly to inform pedagogy, remains a significant challenge. Data from digital sensors that sample at the millisecond level of granularity, such as computer mouses or touchscreens, is notoriously difficult to computationally process and mine for patterns. Adding to the challenge is the limited domain knowledge of this biological sensor level of interaction which prohibits a comprehensive manual feature engineering approach to utilize those data streams. In this paper, we attempt to enhance the assessment capability of a touchscreen-based tutoring system by using Recurrent Neural Networks (RNNs) to predict students’ strategies from their 60hz data streams. We hypothesize that the ability of neural networks to learn representations automatically, instead of relying on human feature engineering, may benefit this classification task. Our classification models (including majority class) were trained and cross-validated at several levels on historical data which had been human coded with learners’ strategies. Our RNN approach to this difficult classification task moderately advances performance above logistic regression. We discuss the implications of this performance for enabling greater tutoring system autonomy. We also present visualizations that illustrate how this neural network approach to modeling sensor data can reveal patterns detected by the RNN. The surfaced patterns, regularized from a larger superset of mostly uncoded data, underscore the mix of normative and seemingly idiosyncratic behavior that characterizes the state space of learning at this high frequency level of observation.
Screening Computed Tomography Angiography to Identify Patients at Low Risk for Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage

Introduction Delayed cerebral ischemia (DCI) occurs during a risk period of 3-21 days following aneurysmal subarachnoid hemorrhage (aSAH) and is associated with worse outcomes. The identification of patients at low risk for DCI might permit triage to less intense monitoring and management. While large-vessel vasospasm (LVV) is a distinct clinical entity from DCI, the presence of moderate-to-severe LVV is associated with a higher risk of DCI. Our hypothesis was that the absence of moderate-to-severe LVV on screening Computed Tomographic Angiography (CTA) performed within the first few days of the DCI risk period will accurately identify patients at low risk for subsequent DCI. Methods This was a retrospective cohort study. Our institutional SAH outcomes registry was queried for all aSAH patients admitted 2016 – 2019 who underwent screening CTA brain between days 4-8 following ictus. We excluded patients diagnosed with DCI prior to the first CTA performed during this time period. All variables are prospectively entered into the registry, and outcomes including DCI and LVV are prospectively adjudicated. We evaluated the predictive value and accuracy of moderate-to-severe LVV on CTA performed 4-8 days following ictus for the prediction of subsequent DCI. Results A total of 243 aSAH patients were admitted during the study timeframe. Of 54 patients meeting eligibility criteria, 11 (20%) had moderate-to-severe LVV on the screening CTA study performed during the risk period. Seven of 11 (64%) patients with moderate-to-severe LVV on the day 4-8 screening CTA, vs. 6 of 43 (14%) patients without, subsequently developed DCI. On multivariate analysis, the presence of LVV on day 4-8 screening CTA was an independent predictor of DCI (Odds Ratio 10.26, 95%CI 1.69-62.24, p=0.011). NPV for the subsequent development of DCI was 86% (95%CI 77-92%). Sensitivity was 54% (25-81%), Specificity 90% (77-97%), and Positive Predictive Value 64% (38-83%). Conclusions The presence of moderate-to-severe LVV on screening CTA performed between days 4-8 following aSAH was an independent predictor of DCI, but achieved only moderate diagnostic accuracy, with NPV 86% and sensitivity 54%. Complementary risk-stratification strategies are likely necessary.
Disaggregating the Power Generation Sector for Input-Output Life Cycle Assessment

The electric power industry plays a critical role in the economy and the environment, and it is important to examine the economic, environmental, and policy implications of current and future power generation scenarios. However, the tools that exist to perform the life cycle assessments are either too complex or too aggregated to be useful for these types of activities. In this work, we build upon the framework of existing input-output (I-O) models by adding data about the electric power industry and disaggregating this single sector into additional sectors, each representing a specific portion of electric power industry operations. For each of these disaggregated sectors, we create a process-specific supply chain and a set of emission factors that allow calculation of the environmental effects of that sector's output. This new model allows a much better fit for scenarios requiring more specificity than is possible with the current I-O model.
Effective thermal property improves phase change paint data

The phase-change coating technique presents itself as a valuable tool in determining the heat transfer rate over the surface of small complex wind tunnel models. A numerical technique is described which shows that an effective thermophysical property - the square root of the product of thermal conductivity, density, and specific heat - may significantly improve the accuracy of the phase-change coating technique with allowance for model inhomogeneity and temperature dependency in a transient environment. Results of the measured steady-state variation of the effective thermophysical property with temperature and the effect of surface heating rate on the effective thermophysical property are plotted for a representative homogeneous model material and for an extreme nonhomogeneous model material. The use of an effective thermophysical property to reduce phase-change paint data is recommended. The analysis also confirms that the apparatus described by Corwin and Kramer (1975) can be used to measure directly this effective thermophysical property for use in wind tunnel model heat-transfer measurements.
INTRODUCTION: REFLECTIONS ON DECADENCE IN THE LATE MING DYNASTY

The late Ming dynasty continues to fascinate, for its strange combination of prosperity and catastrophe. While it may indeed be a certain morbidity in our historical hindsight that compels us to re...
An argument for a runtime layer SPARTA design

Researchers have used advances in hardware technology to design larger and more complex real-time applications. Larger applications require new integration techniques while more complex applications require a restructuring of the underlying system support. We examine the system design issues of supporting SPARTAs (Soft Parallel Real-Time Applications). There exists a gap between hard real-time kernel mechanisms and the functionality desired by a SPARTA programmer. Thus, an integral part of supporting SPARTA design will be providing an intermediate runtime layer. We describe our experiences building Ephor, including what motivated its conception and development, and the resulting separation of responsibilities both easing SPARTA design and improving their performance. >
Parameterization of an effective potential for protein–ligand binding from host–guest affinity data

Force field accuracy is still one of the "stalemates" in biomolecular modeling. Model systems with high quality experimental data are valuable instruments for the validation and improvement of effective potentials. With respect to protein-ligand binding, organic host-guest complexes have long served as models for both experimental and computational studies because of the abundance of binding affinity data available for such systems. Binding affinity data collected for cyclodextrin (CD) inclusion complexes, a popular model for molecular recognition, is potentially a more reliable resource for tuning energy parameters than hydration free energy measurements. Convergence of binding free energy calculations on CD host-guest systems can also be obtained rapidly, thus offering the opportunity to assess the robustness of these parameters. In this work, we demonstrate how implicit solvent parameters can be developed using binding affinity experimental data and the binding energy distribution analysis method (BEDAM) and validated using the Grid Inhomogeneous Solvation Theory analysis. These new solvation parameters were used to study protein-ligand binding in two drug targets against the HIV-1 virus and improved the agreement between the calculated and the experimental binding affinities. This work illustrates how benchmark sets of high quality experimental binding affinity data and physics-based binding free energy models can be used to evaluate and optimize force fields for protein-ligand systems. Copyright © 2015 John Wiley & Sons, Ltd.
Reactions of cobalt clusters with deuterium

The kinetics of chemical reactions of cobalt clusters Con with deuterium are described. Absolute rate constants have been measured in the size range n=7–68 at 293 K. The rate constants are found to be a strong function of cluster size, varying by a factor of 400. This size dependence is most prominent for n=7 to 25: Co15 is the most reactive cluster, and Co7–9 and Co19–20 are particularly unreactive. Abrupt changes in the rate constants from one cluster size to the next are observed. For the clusters above n=25, the rate constants show several less prominent maxima and minima superimposed on a slow, nearly monotonic increase with cluster size.
Brunner's gland adenoma of the duodenum.

Three cases of large, polypoid Brunner's gland adenoma are reported. These tumors arise from glandular tissue in the duodenum and often are associated with bleeding and abdominal discomfort. The radiologic, clinical, and pathologic features are reviewed.
Abstract A3: Facilitating epithelial to mesenchymal transition through inhibition of senescence checkpoint functions

Transforming growth factor (TGF)‐β is a potent inducer of epithelial to mesenchymal transition (EMT). However, EMT is not a sole consequence of TGF‐β mediated stimulation. It remains unclear as to what determines the underlying cellular capacity to undergo EMT in response to TGF‐β. Overexpression of epidermal growth factor receptor (EGFR) and mutations in tumor suppressor p53 are common in the early stage of esophageal carcinogenesis and required for transformation and invasive growth of human esophageal epithelial cells. EGFR overexpression and mutant p53 appear to be key determinants in facilitating TGF‐β-induced EMT. EGFR tyrosine kinase activity was dispensable for EMT. However, EGFR overexpression fated the esophageal cells to EMT through induction of ZEB1 and ZEB2, zinc finger E‐box binding proteins which evade EGFR‐mediated oncogenic as well as the TGF‐β-activated senescence responses by inhibiting p15 INK4b and p16 INK4a . Mutant p53 limits TGF‐β-induced senescence by suppressing the p53‐dependent senescence checkpoint function. When senescence was negated, TGF‐β prompted EMT through induction of ZEB1 and ZEB2 along with concomitant downregulation of the microRNA‐200 family. Thus, genetic lesions may involve not only suppression of senescence checkpoint functions but also reactivation of the cellular EMT program in the early stages of carcinogenesis. Citation Information: Cancer Res 2009;69(23 Suppl):A3.
Immunodiffusion systematics of the primates. III. The strepsirhini.

Immunodiffusion comparisons have been run using 26 antisera including seven made to strepsirhine species. Spur size data resulting from these comparisons have been analyzed by computer and depict Stre
New Particle Formation and Growth in the Troposphere

The formation and growth of nanoparticles in the atmosphere has important implications for human health and global climate. Understanding the chemistry behind these processes requires development and deployment of innovative analytical methods.
The Americanisation of George Washington

(1992). The Americanisation of George Washington. History of European Ideas: Vol. 15, No. 1-3, pp. 419-425.
The relative contributions of non-enzymatic glycation and cortical porosity on the fracture toughness of aging bone

The risk of fracture increases with age due to the decline of bone mass and bone quality. One of the age-related changes in bone quality occurs through the formation and accumulation of advanced glycation end-products (AGEs) due to non-enzymatic glycation (NEG). However as a number of other changes including increased porosity occur with age and affect bone fragility, the relative contribution of AGEs on the fracture resistance of aging bone is unknown. Using a high-resolution nonlinear finite element model that incorporate cohesive elements and micro-computed tomography-based 3d meshes, we investigated the contribution of AGEs and cortical porosity on the fracture toughness of human bone. The results show that NEG caused a 52% reduction in propagation fracture toughness (R-curve slope). The combined effects of porosity and AGEs resulted in an 88% reduction in propagation toughness. These findings are consistent with previous experimental results. The model captured the age-related changes in the R-curve toughening by incorporating bone quantity and bone quality changes, and these simulations demonstrate the ability of the cohesive models to account for the irreversible dynamic crack growth processes affected by the changes in post-yield material behavior. By decoupling the matrix-level effects due to NEG and intracortical porosity, we are able to directly determine the effects of NEG on fracture toughness. The outcome of this study suggests that it may be important to include the age-related changes in the material level properties by using finite element analysis towards the prediction of fracture risk.
Determination of 3'-azido-2',3'-dideoxyuridine in maternal plasma, amniotic fluid, fetal and placental tissues by high-performance liquid chromatography.

Abstract 3′-Azido-2′,3′-dideoxyuridine (AZDU, Azddu, CS-87) is a nucleoside analog of 3′-azido-3′-deoxythymidine (zidovudine, AZT) that has been shown to inhibit human immunodeficiency virus (HIV-1). AZDU is a potential candidate for treatment of pregnant mothers to prevent prenatal transmission of HIV/AIDS to their unborn children. A rapid and efficient high-performance liquid chromatography (HPLC) method for the determination of AZDU concentrations in rat maternal plasma, amniotic fluid, placental and fetal tissue samples has been developed and validated. Tissue samples were homogenized in distilled water, protein precipitated and extracted using a C-18 solid-phase extraction (SPE) method prior to analysis. Plasma and amniotic fluid samples were protein precipitated with 2 M perchloric acid prior to analysis. Baseline resolution was achieved using a 4.5% acetonitrile in 40 m M sodium acetate (pH 7) buffer mobile phase for amniotic fluid, placenta and fetus samples and with a 5.5% acetonitrile in buffer solution for plasma at flow-rates of 2.0 ml/min. The HPLC system consists of a Hypersil ODS column (150×4.6 mm) with a Nova-Pak C-18 guard column with detection at 263 nm. The method yields retention times of 6.2 and 12.2 min for AZDU and AZT in plasma and 8.3 and 17.6 min for AZDU and AZT in amniotic fluid, fetal and placental tissues. Limits of detection ranged from 0.01 to 0.075 μg/ml. Recoveries ranged from 81 to 96% for AZDU and from 82 to 96% for AZT in the different matrices. Intra-day ( n =6) and inter-day ( n =9) precision (% RSD) and accuracy (% Error) ranged from 1.48 to 6.25% and from 0.50 to 10.07%, respectively.