cssi/SciSciGPT-SciSciNet huggingface dataset:
Whole Genome Sequence Analysis Using JSpecies Tool Establishes Clonal Relationships between Listeria monocytogenes Strains from Epidemiologically Unrelated Listeriosis Outbreaks.

In an effort to build a comprehensive genomic approach to food safety challenges, the FDA has implemented a whole genome sequencing effort, GenomeTrakr, which involves the sequencing and analysis of genomes of foodborne pathogens. As a part of this effort, we routinely sequence whole genomes of Listeria monocytogenes (Lm) isolates associated with human listeriosis outbreaks, as well as those isolated through other sources. To rapidly establish genetic relatedness of these genomes, we evaluated tetranucleotide frequency analysis via the JSpecies program to provide a cursory analysis of strain relatedness. The JSpecies tetranucleotide (tetra) analysis plots standardized (z-score) tetramer word frequencies of two strains against each other and uses linear regression analysis to determine similarity (r2). This tool was able to validate the close relationships between outbreak related strains from four different outbreaks. Included in this study was the analysis of Lm strains isolated during the recent caramel apple outbreak and stone fruit incident in 2014. We identified that many of the isolates from these two outbreaks shared a common 4b variant (4bV) serotype, also designated as IVb-v1, using a qPCR protocol developed in our laboratory. The 4bV serotype is characterized by the presence of a 6.3 Kb DNA segment normally found in serotype 1/2a, 3a, 1/2c and 3c strains but not in serotype 4b or 1/2b strains. We decided to compare these strains at a genomic level using the JSpecies Tetra tool. Specifically, we compared several 4bV and 4b isolates and identified a high level of similarity between the stone fruit and apple 4bV strains, but not the 4b strains co-identified in the caramel apple outbreak or other 4b or 4bV strains in our collection. This finding was further substantiated by a SNP-based analysis. Additionally, we were able to identify close relatedness between isolates from clinical cases from 1993–1994 and a single case from 2011 as well as links between two isolates from over 30 years ago. The identification of these potential links shows that JSpecies Tetra analysis can be a useful tool in rapidly assessing genetic relatedness of Lm isolates during outbreak investigations and for comparing historical isolates. Our analyses led to the identification of a highly related clonal group involved in two separate outbreaks, stone fruit and caramel apple, and suggests the possibility of a new genotype that may be better adapted for certain foods and/or environment.
Diagnostic Shoulder Arthroscopy and Arthroscopic Anatomy

Shoulder arthroscopy is a common procedure in orthopedic surgery. It is becoming more popular with advancements in technology and instrumentation. The number of shoulder disorders being treated arthroscopically has increased steadily in recent years. Shoulder arthroscopy has many uses today, spanning from diagnostic arthroscopy to complex reconstructive procedures. In addition to glenohumeral arthroscopy, subacromial arthroscopy has also expanded in the past two decades. More recently, subdeltoid arthroscopy is being utilized as a newer way to access the anterior shoulder. As with any surgery, a thorough understanding of the normal anatomy and common variations is important, but more so in shoulder arthroscopy as fluid extravasation and swelling may distort anatomic landmarks and potentially lead to increased complications and neurologic injury. Many decisions need to be made prior to an arthroscopic shoulder procedure. These include selection of anesthesia, patient positioning, and portal use. This chapter will discuss the various options and considerations for shoulder arthroscopy. In addition, it will aid in portal selection, go over a diagnostic shoulder arthroscopy, and discuss the pertinent applied anatomy of the shoulder.
Close-coupling calculation for the 2Σu+}state of H2-

We demonstrate the utility of the close-coupling approximation, usually applied to scattering problems, for calculations of molecular bound states. Our primary test case is the $^{2}\mathrm{\ensuremath{\Sigma}}_{\mathit{u}}^{+}$ state of ${\mathrm{H}}_{2}^{\mathrm{\ensuremath{-}}}$. While limited to Hartree-Fock accuracy, our analysis of this resonant state within the bound region parallels closely the results from more precise quantum-chemical calculations. Specifically, the crossing between the neutral and negative-ion curves occurs at an internuclear separation of 3.025 a.u. in our calculation, in good agreement with a multireference configuration-interaction approach of previous authors. The shape and total energy of the anion curve, when corrected for by the correlation energy of the target at the crossing, is also in good agreement with earlier results. The method is then extended into the unbound or resonant-state region by studying the shape-resonance behavior of scattering eigenphase sums.
Instrumentation for Thin-Layer Chromatography: A Review

Description des etapes successives de la chromatographie en couche mince et tableaux pratiques recapitulatifs des fabricants d'appareillage
Small-Scale Thrust Augmentation Analysis of Cold Flow Ejector/ Diffuser Assembly

The application of an ejector fitted with a diffuser is used to transfer momentum from a high speed primary flow to an entrained secondary flow to increase the overall thrust of the system. The increase in thrust is due to a greater propulsive efficiency achieved by trading exit velocity for overall mass flow. The objective of this project was to understand the effects of varying the primary nozzle and ejector exit flow areas on overall ejector/diffuser performance. Three primary flow nozzles were tested in combination with four diffuser exit diameters. Thrust augmentation was found to increase as the ratio of the secondary to primary flow areas increased and as the ratio of diffuser exit area to mixer areas increased. A maximum thrust augmentation of 1.5 was achieved with the smallest diameter primary flow nozzle and the largest diameter diffuser exit.
The Standards by Which the Spotless Phase of Hippodamia Convergens Is Judged

It has been suggested by a specialist in the Coleoptera that the sizes of spots used in my ratings of the pattern of Hippodamia convergens (Coccinellidae) (Shull, 1944) should be put on record in order that others may more effectively distinguish the spotless phase in their collections. Students of this species will know, and others will easily understand, that the so-called “spotless” beetles often have spots. They could hardly have expected, until genetic work was done on the contrasted patterns, that spotless beetles (possessors of the dominant spotless gene) of certain lines of descent could as closely resemble the spotted ones as they were found to do.
On the Er Ren Tai Pai Zi Qu

Er Ren Tai Pai Zi Qu is the folk Sizhu music of the west part of Inner Mongolia with the most influence and popularity and it is earlier than the formation of Er Ren Tai.The melody patterns were multi-originated with both the remains of ancient music and the evolution from Mongolian folk songs and Chinese folk music together with the absorbing of some religious music.It is the art crystal of both the Central plain Chinese immigration music culture and the local Mongolian folk music culture.
A swollen thumb.

A 78-year-old man with a history of diabetes mellitus and hypertension presented with a four-month history of progressively worsen- ing, painless swelling at the base of his left thumbnail. The swelling was accompanied by a serosanguineous discharge at the cuticle. There was no history of trauma to the area. Treatment with levofloxacin (Levaquin), 500 mg, for 10 days was ineffective. Physical examination revealed hyperpig- mented skin just below the cuticle of the left thumb with swelling (see accompanying figure). The base of the nail appeared fleshy with loss of the cuticle and dystrophy of the nail plate. Question
Cartilage Therapy and Repair in Equine Athletes

The status of articular cartilage often defines the level, progression, and subsequent prognosis of joint disease in both human and equine athletes. Although methods to diagnose equine cartilage defects have significantly improved over the past decade, articular cartilage damage and ensuing osteoarthritis remain a challenge to treat. The following 2 categories of surgical options for cartilage repair in the horse are typically considered: palliative and reparative or restorative. Palliative surgical care consists of arthroscopic debridement and lavage, whereas reparative options involve the use of marrow stimulation techniques. Restorative or reparative surgical options are an area of active research, including the use of osteochondral grafting, autologous chondrocyte implantation (ACI), and augmentation with mesenchymal stem cells (MSCs). Subchondral bone microfracture coupled with intra-articular stem cell injection is currently considered to be the optimal treatment combination for equine patients with articular cartilage defects. Following arthroscopic surgery, the rehabilitative goals are to provide support to the affected limb, restore joint flexibility, stability, and manage perioperative pain. In addition, biologic therapy for the treatment of equine joint disease continues to be clinically employed and of investigational interest. With the large amount of ongoing in vitro research in bioprinted osteochondral constructs and potential extracellular matrix components, and the advantages of the in vivo equine model of articular cartilage repair as well as naturally occurring disease, it seems inevitable that the horse would be used to develop these novel techniques.
Impact of Flap Reconstruction on Radiotoxicity After Salvage Surgery and Reirradiation for Recurrent Head and Neck Cancer

Background Recurrent head and neck malignancies remain a therapeutic challenge. Tissue transfer, in addition to defect coverage and prevention of wound complications, may potentially decrease radiotoxicity. We evaluated radiation toxicity and survival outcomes of patients who underwent salvage surgery with reirradiation, comparing primary closure to flap reconstruction.
SOME THEORIES THAT HAVE BEEN ADVANCED TO EXPLAIN THE POLARITY OF THE SMALL BOWEL

This chapter discusses some theories that have been advanced to explain the polarity of the small bowel. The bowel is polarized in that it transmits fluids and solids more easily in one direction than in the other. The currently accepted explanation of the polarity of the bowel is found in Bayliss and Starling's “law of the intestine,” or the myenteric reflex. The idea is that food goes down the bowel because, when cerebrospinal reflexes are excluded, excitation at any point excites contraction above and inhibition below. The animal used should be a dog, purged with castor oil, with the bowel denervated and with balloons in it. In several thousand experiments it was found that, in the small bowel of the rabbit stimulated electrically on its serous surface, the response in both longitudinal and circular muscle is almost always contraction locally, above and below. Contraction above and relaxation below is a rare occurrence.
Highly compact fiber Fabry-Perot interferometer: A new instrument design

This paper presents the design, construction, and characterization of a new optical-fiber-based, low-finesse Fabry-Perot interferometer with a simple cavity formed by two reflecting surfaces (the end of a cleaved optical fiber and a plane, reflecting counter-surface), for the continuous measurement of displacements of several nanometers to several tens of millimeters. No beam collimation or focusing optics are required, resulting in a displacement sensor that is extremely compact (optical fiber diameter 125 μm), is surprisingly tolerant of misalignment (more than 5°), and can be used over a very wide range of temperatures and environmental conditions, including ultra-high-vacuum. The displacement measurement is derived from interferometric phase measurements using an infrared laser source whose wavelength is modulated sinusoidally at a frequency f. The phase signal is in turn derived from changes in the amplitudes of demodulated signals, at both the modulation frequency, f, and its harmonic at 2f, coming from a photodetector that is monitoring light intensity reflected back from the cavity as the cavity length changes. Simple quadrature detection results in phase errors corresponding to displacement errors of up to 25 nm, but by using compensation algorithms discussed in this paper, these inherent non-linearities can be reduced to below 3 nm. In addition, wavelength sweep capability enables measurement of the absolute surface separation. This experimental design creates a unique set of displacement measuring capabilities not previously combined in a single interferometer.
Producer Exploration can Generate Categories without Audiences

Category theory argues that markets function as an interface between producer candi- dates and audiences that evaluate those candidates. Audiences lump similar producer into categories in order to ...
Laser Atherectomy Combined With Drug-Coated Balloon Angioplasty Is Associated With Improved 1-Year Outcomes for Treatment of Femoropopliteal In-Stent Restenosis:

Purpose: To examine whether laser atherectomy combined with drug-coated balloons (laser + DCB) can improve the outcomes of femoropopliteal (FP) in-stent restenosis (ISR). Methods: A dual-center ret...
Gene expression profiles of the meniscus avascular phenotype: A guide for meniscus tissue engineering.

Avascular (Avas) meniscus regeneration remains a challenge, which is partly a consequence of our limited knowledge of the cells that maintain this tissue region. In this study, we utilized microarrays to characterize gene expression profiles of intact human Avas meniscus tissue and of cells following culture expansion. Using these data, we examined various 3D culture conditions to redifferentiate Avas cells toward the tissue phenotype. RNA was isolated from either the tissue directly or following cell isolation and 2 weeks in monolayer culture. RNA was hybridized on human genome arrays. Differentially expressed (DE) genes were identified by ranking analysis. DAVID pathway analysis was performed and visualized using STRING analysis. Quantitative PCR (qPCR) on additional donor menisci (tissues and cells) were used to validate array data. Avas cells cultured in 3D were subjected to qPCR to compare with the array-generated data. A total of 387 genes were DE based on differentiation state (>3-fold change; p < 0.01). In Avas-cultured cells, the upregulated pathways included focal adhesion, ECM-receptor interaction, regulation of actin cytoskeleton, and PDGF Signaling. In 3D-cultured Avas cells, TGFβ1 or combinations of TGFβ1 and BMP6 were most effective to promote an Avas tissue phenotype. THBS2 and THBS4 expression levels were identified as a means to denote meniscus cell phenotype status. We identified the key gene expression profiles, new markers and pathways involved in characterizing the Avas meniscus phenotype in the native state and during in vitro dedifferentiation and redifferentiation. These data served to screen 3D conditions to generate meniscus-like neotissues. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1947-1958, 2018.
The effect of a service dog on salivary cortisol awakening response in a military population with posttraumatic stress disorder (PTSD)

Recent studies suggest a therapeutic effect of psychiatric service dogs for military veterans with posttraumatic stress disorder (PTSD), but are limited by self-report biases. The current study assessed the effect of PTSD service dogs on the salivary cortisol awakening response (CAR) and arousal-related functioning in a population of military veterans with PTSD. Participants included 73 post-9/11 military veterans with PTSD including 45 with a service dog and 28 on the waitlist to receive one. Saliva samples were collected on two consecutive weekday mornings at awakening and 30 min later to quantify the cortisol awakening response (CAR) and its area under the curve (AUCi) in addition to standardized survey measures of anxiety, anger, sleep quality and disturbance, and alcohol abuse. There was a significant main effect of having a service dog on both the CAR and the AUCi, with individuals with a service dog exhibiting a higher CAR and AUCi compared to those on the waitlist. Results also revealed that those with a service dog reported significantly lower anxiety, anger, and sleep disturbance as well as less alcohol abuse compared to those on the waitlist, with medium to large effect sizes. Although those with a service dog reported significantly less PTSD symptom severity, CAR was not significantly associated with PTSD symptoms within or across group. In conclusion, results indicate that the placement of a PTSD service dog may have a significant positive influence on both physiological and psychosocial indicators of wellbeing in military veterans with PTSD. Although clinical significance cannot be confirmed, a higher CAR/AUCi among those with a service dog may indicate better health and wellbeing in this population. Future within-subject, longitudinal research will be necessary to determine potential clinical significance and impact of individual differences.
Potential Effect of Cyclophosphamide on Bleb Survival in Five Patients with Multiple Sclerosis Who Underwent Glaucoma Surgery

The purpose of this case series was to report the potential role of cyclophosphamide (CY) on bleb survival and to evaluate the safety of the trabeculectomy procedure under immunosuppressant systemic therapy. Five eyes of five patients with unresponsive to intraocular pressure (IOP) lowering medication, progressive glaucoma, underwent mytomicin C (MMC) augmented phaco-trabeculectomy, performed by the same surgeon, A.G., during the period from May 2015 to January 2016. All patients were treated with low doses of systemic CY at the time of surgery, to control their relapsing progressive multiple sclerosis (MS) form. During a mean follow-up period of 20.6 ± 8.1 months, for cases of “complete success” (when the IOP was < 15 mmHg without glaucoma therapy) were observed, while one case was classified as a “qualified success” since the IOP was ≤ 15 mmHg with β-blocker drops. There were no bleb infections, nor bleb-related complications. This study reports the safety of performing the filtration surgical procedure under immunosuppressant systemic therapy and provides a possible explication of CY anti-fibrotic mechanism and its possible role on bleb survival. Our findings may suggest new perspectives of study in this field.
An Overview of Inflammation

Inflammation is the reaction of tissues to injury and is designed to eliminate the cause of damage and pave the way for healing. A particularly important purpose of an inflammatory response is to provide a first line of defense against infection. The clinical signs of acute inflammation (redness, swelling, heat, and pain) have been recognized since antiquity. Three major physiological changes occur in inflamed tissues. Dilation of blood vessels increases the flow of blood to the area of damage, whereas increased permeability of the vessel wall allows plasma constituents to enter the surrounding injured tissue. Circulating white blood cells also emigrate from the blood to the tissues, where they clear microbes and debris and initiate reactions of the immune response. Collectively, these changes deliver to a damaged tissue the components that are needed to deal with the insult. A complicated network of cells and chemical mediators must cooperate first to ignite the reactions of inflammation and then to dampen them when the crisis has been resolved. Inflammation is intended to benefit the body, and most often, it fulfills this goal. However, an inflammatory response can go awry, resulting in collateral damage to healthy tissues and exacerbation of disease.
Diagnostic for Verifying the Thrust Vector Requirement of the AEPS Hall-Effect Thruster and Comparison to the NEXT-C Thrust Vector Diagnostic

A diagnostic has been designed and fabricated to verify the thrust vector requirement for the Advanced Electric Propulsion System (AEPS) Hall Effect Rocket with Magnetic Shielding (HERMeS) thruster. This diagnostic will be used to verify that the propulsion system thrust vector offset from the mounting surface normal vector does not exceed 1.5 degrees over the entire throttling range and over the course of 23,000 hours of thruster testing. The diagnostic will also not violate the thruster's required voltage standoff capability in the presence of carbon backsputter by being minimally intrusive and not significantly adding to the facility backsputtered rate. Based on these requirements, an appropriate diagnostic design was determined to comprise of an array of 23 Faraday probes swept through the plume in an arc 1m from the thruster to map the beam current density. The beam current density centroid of the plume is assumed to track the thrust vector within an acceptable level of uncertainty. Additionally, a reference system, including optical alignment to the mounting surface normal vector and tilt sensors, was devised to periodically calibrate the probe position and motion throughout the long duration wear test campaign. Initial measurements of the thruster plume have been acquired to demonstrate the diagnostics functionality, verify procedures, and assess any necessary improvements prior to implementation of the diagnostic during the AEPS Engineering Development Unit (EDU) long duration wear test. To illustrate the merits of differing approaches to thrust vector determination for different classes of electric propulsion thrusters, NASA's Evolutionary Xenon Thruster-Commercial (NEXT-C) thrust vector diagnostic design details and recent data are also discussed (Appendix A).
Use of NO Chemisorption for the Study of Catalyst Support Interactions

Previously it was shown that nitric oxide chemisorbs on a series of supported transition metal surface ions at room temperature, with one NO molecule being adsorbed per surface ion. The study of NO chemisorption on supported cobalt and nickel oxides has been pursued further to characterize the catalyst-support interactions. On cobalt aluminate the chemisorption was found to be very small. This was explained by the shielding of the tetrahedrally coordinated cobaltous ions from the surface by the oxygen ions in this spinel compound. The explanation is supported by the ion-scattering spectra of the COA12O4 surface. Measurement of the NO uptake of cobalt and nickel oxide catalysts variously supported, after heat-treatments at successively increasing temperatures, has revealed the different character of the support-catalyst interaction. On zirconia, the area of the NO uptake reaches the value of the BET area. On alumina, there is diffusion of the cobalt or nickel ions into the bulk of the support accompanied by spinel formation. Diffusion into the bulk occurs also, to some degree, on preformed cobalt-aluminate support. The supported cobalt and nickel catalysts represent complex systems and at low metal ion loadings on a zirconia support, multiple NO adsorption on a surface metal ion was noted.
Favoring 'Home Grown Power': Do the RPS Modifications Contained in the Massachusetts' Green Communities Act of 2008 Violate the Commerce Clause?

The shift to a greater blend of domestically harvested, local, decentralized renewable power is characterized not just as a climate change necessity, but also as the dawn of a clean energy economy. Concerned about losing the potential benefits of this sea change in energy sourcing and supply, many states have built protections for local resource types into their state renewable portfolio standards. But, what are the implications for interstate commerce when a state sets up energy markets or regulatory regimes that serve to afford differential treatment to out-of-state resources? The paper looks at the Dormant Commerce Clause through the lens of the Massachusetts' RPS as amended by the Green Communities Act of 2008, and asks whether a system that provides Renewable Energy Credits with an eye towards an energy supplier's geographic origin can past constitutional muster.
Fundamentals of Automobile Body Structure Design

Provides comprehensive coverage of the fundamental principles of automobile body structure design. The focus is on creation of a body structure concept rather than analysis, and the models presented are intended to give the reader insight into the behaviour of body structural systems not available from complex analysis tools such as finite elements analysis.
Influence of carcinoid syndrome on the clinical characteristics and outcomes of patients with gastroenteropancreatic neuroendocrine tumors undergoing operative resection.

Background The incidence, clinical characteristics, and long-term outcomes of patients with gastroenteropancreatic neuroendrocrine tumors and carcinoid syndrome undergoing operative resection have not been well characterized. Methods Patients undergoing resection of primary or metastatic gastroenteropancreatic neuroendrocrine tumors between 2000 and 2016 were identified from an 8-institution collaborative database. Clinicopathologic and postoperative characteristics as well as overall survival and disease-free survival were compared among patients with and without carcinoid syndrome. Results Among 2,182 patients who underwent resection, 139 (6.4%) had preoperative carcinoid syndrome. Patients with carcinoid syndrome were more likely to have midgut primary tumors (44.6% vs 21.4%, P Conclusion Among patients undergoing operative resection of gastroenteropancreatic neuroendrocrine tumors, the prevalence of preoperative carcinoid syndrome was low. Although operative intervention with resection or especially debulking in patients with carcinoid syndrome was disappointing and often failed to improve symptoms, after controlling for markers of tumor burden, carcinoid syndrome was not independently associated with worse disease-free survival or overall survival.
Achievement of English as New Language Learners in Monitor Status: A Cross Sector Comparison from Denver.

ABSTRACTThis study uses administrative data to measure the effect of attending a charter school in Denver, Colorado on the achievement of reclassified English as New Language (ENL) students during ...
Reiterating Performatives: The Writer, the Reader and the Risks of Literary Action

“Reiterating Performatives” turns to theoretical work by Jacques Derrida and critical work by Edwidge Danticat to fashion a more capacious, inclusive theory of the writer, and of writing, than those usually understood to have been offered historically by either traditional literary criticism or the strains of post-structural theory that have put that criticism under such acute interrogation over the past fifty years. Without losing sight of the question of latinidad introduced in the previous section, this section focuses primarily on the question of the literary through its analysis of the figure and the work of the writer.
Psychometric Characteristics of the DANVA-2 in High-Functioning Children with ASD.

This study examined psychometric characteristics of the Diagnostic Analysis of Nonverbal Accuracy—Second Edition (DANVA-2) in 121 children, ages 6 to 13 years, with high-functioning autism spectrum disorder (HFASD). Internal consistency for adult and child faces subtests were .70 and .75, respectively. Immediate test–retest reliability in the total sample (N = 121) ranged from .78 to .84. Reliability for two subsamples for 5- (n = 21) and 12-week (n = 21) intervals ranged from .75 to .90 and from .43 to .68, respectively. DANVA-2 scores strongly converged with two measures of emotion recognition but were unrelated to parent ratings of social functioning and ASD symptoms. Significant correlations (small to medium) were found between DANVA-2 scores and child age, IQ, and language ability.
Neurotensin as a source of cyclic AMP and co-mitogen in fibrolamellar hepatocellular carcinoma.

// Kimberly J. Riehle 1 , Heidi L. Kenerson 1 , Kevin M. Riggle 1 , Rigney Turnham 2 , Kevin Sullivan 1 , Renay Bauer 1 , John D. Scott 2 and Raymond S. Yeung 1 1 Department of Surgery, University of Washington, Seattle, WA, USA 2 Department of Pharmacology, University of Washington, Seattle, WA, USA Correspondence to: Kimberly J. Riehle, email: kriehle@uw.edu Keywords: liver cancer; protein kinase A; fibrolamellar; neurotensin; epidermal growth factor Received: March 04, 2019 Accepted: July 28, 2019 Published: August 20, 2019 ABSTRACT Fibrolamellar hepatocellular carcinomas (FL-HCCs) possess a unique mutation that encodes a chimeric form of protein kinase A (DNAJ-PKAc), which includes a chaperonin binding domain. DNAJ-PKAc retains most of the biochemical properties of the native enzyme, however, and activity remains dependent on cAMP. We thus speculated that a persistent source of cAMP is necessary to promote FL-HCC carcinogenesis, and that neurotensin (NTS) may drive cAMP production in this setting, given that NS serum and tumor levels are elevated in many patients with FL-HCC. We examined expression of NTS pathway components in human FL-HCCs and paired normal livers, and determined the role of NTS in driving proliferation in tumor slice cultures. Cultured hepatocytes were used to determine interactions between NTS and other proliferative pathways, and to determine the effects of NTS on cAMP production and PKA activity. We found that the NTS pathway is up-regulated in human FL-HCCs, and that NTS activates cAMP and PKA in hepatocytes. NTS increases proliferation in the presence of epidermal growth factor (EGF), and NTS-induced proliferation is dependent on NTSR1 and the EGFR/MEK pathway. We conclude that NTS serves as a co-mitogen in FL-HCC, and provides a source of cAMP to facilitate ongoing activation of DNAJ-PKAc.
High molecular weight DNA isolation method from diverse plant species for use with Oxford Nanopore sequencing

Abstract The ability to generate long reads on the Oxford Nanopore Technologies sequencing platform is dependent on the isolation of high molecular weight DNA free of impurities. For some taxa, this is relatively straightforward; however, for plants, the presence of cell walls and a diverse set of specialized metabolites such as lignin, phenolics, alkaloids, terpenes, and flavonoids present significant challenges in the generation of DNA suitable for production of long reads. Success in generating long read lengths and genome assemblies of plants has been reported using diverse DNA isolation methods, some of which were tailored to the target species and/or required extensive labor. To avoid the need to optimize DNA isolation for each species, we developed a taxa-independent DNA isolation method that is relatively simple and efficient. This method expands on the Oxford Nanopore Technologies high molecular weight genomic DNA protocol from plant leaves and utilizes a conventional cetyl trimethylammonium bromide extraction followed by removal of impurities and short DNA fragments using commercially available kits that yielded robust N50 read lengths and yield on Oxford Nanopore Technologies flow cells.
Endothelial Cells Derived from Human Vessel Walls Contain a Complete Hierarchy of Endothelial Progenitor Cells.

Endothelial progenitor cells (EPCs) can be isolated from adult peripheral and umbilical cord blood. EPCs are thought to originate from bone marrow, circulate in peripheral blood, and migrate to sites of angiogenesis. However, the number of circulating EPCs in peripheral blood is remarkably low, and recent genetic studies show that the contribution of bone marrow derived EPCs to newly formed vascular networks is minimal. Further, while endothelial cells (ECs) derived from vessel walls are widely considered to be differentiated mature ECs, these cells retain extensive proliferative potential and can be passaged for at least 40 population doubling in vitro. Based on these observations, we tested whether EPCs potentially reside in vessel walls utilizing a newly developed single cell deposition assay (Blood, 2004). Analogous to a paradigm established in the hematopoietic cell system, we can utilize this assay to reproducibly identify the following EPCs: (1) high proliferative potential - endothelial colony forming cells (HPP-ECFC), which form macroscopic colonies that form secondary and tertiary colonies upon replating, (2) low proliferative potential - endothelial colony forming cells (LPP-ECFC), which form colonies greater than 50 cells, but do not form secondary colonies upon replating, (3) endothelial cell clusters (EC-clusters) that contain less than 50 cells, and (4) mature terminally differentiated endothelial cells (EC), which do not divide. Utilizing this assay, we compared the clonogenic potential of 1000 single adult human dermal microvascular endothelial cells (HMVECds), human umbilical vein endothelial cells (HUVECs), human umbilical artery endothelial cells (HUAECs), human coronary artery endothelial cells (HCAECs), and human aortic endothelial cells (HAECs) to the potential of adult peripheral and umbilical cord blood derived EPCs. We conducted four independent experiments. Remarkably, we demonstrate that a complete hierarchy of EPCs can be identified in EC populations derived from every vessel wall tested (Table I and n=4). Further, we show that ECs derived from each vessel wall cell population tested contain more proliferative EPCs (LPP-ECFCs and HPP-ECFCs) compared to EPCs derived from adult peripheral blood. Percent of 1,000 Single Cells Plated | | Mature EC | EC-Cluster | LPP-ECFC | HPP-ECFC | |:--------- | --------- | ---------- | -------- | -------- | | HUVEC | 42±6 | 18±2 | 29±9 | 11±5 | | HAEC | 37±3 | 23±8 | 21±4 | 20±6 | | HMVECd | 65±9 | 21±6 | 12±4 | 2±0.6 | | HCAEC | 46±2 | 18±2 | 20±2 | 16±2 | | HUAEC | 41±1 | 10±1 | 27±4 | 21±2 | | Adult EPC | 81±9 | 9±1 | 12±8 | 0.2±0.2 | | Cord EPC | 50±20 | 7±2 | 20±10 | 23±9 | Thus, this study provides evidence that a diversity of EPCs exists in human vessels and provides a new conceptual framework for determining both the origin and function of EPCs in maintaining vessel integrity and contributing to new sites of angiogenesis.
Decarbonizing agriculture through the conversion of animal manure to dietary protein and ammonia fertilizer

The decarbonization of agriculture faces many challenges and has received a level of attention insufficient to abate the worst effects of climate change and ensure a sustainable bioeconomy. Agricultural emissions are caused both by fossil-intensive fertilizer use and land-use change, which in turn are driven in part by increasing demand for dietary protein. To address this challenge, we present a synergistic system in which organic waste-derived biogas (a mixture of methane and carbon dioxide) is converted to dietary protein and ammonia fertilizer. This system produces low-carbon fertilizer inputs alongside high-quality protein, addressing the primary drivers of agricultural emissions. If the proposed system were implemented across the United States utilizing readily available organic waste from municipal wastewater, landfills, animal manure, and commercial operations, we estimate 30% of dietary protein intake and 127% of ammonia usage could be displaced while reducing land use, water consumption, and greenhouse gas emissions.
Network Data Analysis to Support Risk Management in an IoT Environment

The expansion of the internet of things (IoT) across the world has created security concerns for organizations and consumers alike. Numerous researchers have shown that IoT vulnerabilities are increasing and that tools should be used to stop them or detect them. This paper explores the use of data analysis to help organizations manage the security of IoT networks using the National Institute of Standards and Technology (NIST) Risk Management Framework (RMF). This paper does not concentrate on the end tool, but rather demonstrates the ability to analyze IoT traffic and discern whether or not an attack has been carried out or is in progress. We focus on the ‘monitor’ portion of the framework and demonstrate data analysis of whether an attack has been carried out. We use machine learning and analytical tools to accomplish this analysis. Knowing what the attack looks like allows for practical applications of toolsets.
Prospective Double-Blinded Randomized Field-Based Clinical Trial of Metoclopramide and Ibuprofen for the Treatment of High Altitude Headache and Acute Mountain Sickness

Introduction High altitude headache (HAH) and acute mountain sickness (AMS) are common pathologies at high altitudes. There are similarities between AMS and migraine headaches, with nausea being a common symptom. Several studies have shown ibuprofen can be effective for AMS prophylaxis, but few have addressed treatment. Metoclopramide is commonly administered for migraine headaches but has not been evaluated for HAH or AMS. We aimed to evaluate metoclopramide and ibuprofen for treatment of HAH and AMS. Methods We performed a prospective, double-blinded, randomized, field-based clinical trial of metoclopramide and ibuprofen for the treatment of HAH and AMS in 47 adult subjects in the Mount Everest region of Nepal. Subjects received either 400 mg ibuprofen or 10 mg metoclopramide in a 1-time dose. Lake Louise Score (LLS) and visual analog scale of symptoms were measured before and at 30, 60, and 120 min after treatment. Results Subjects in both the metoclopramide and ibuprofen arms reported reduced headache severity and nausea compared to pretreatment values at 120 min. The ibuprofen group reported 22 mm reduction in headache and 6 mm reduction in nausea on a 100 mm visual analog scale at 120 min. The metoclopramide group reported 23 mm reduction in headache and 14 mm reduction in nausea. The ibuprofen group reported an average 3.5-point decrease on LLS, whereas the metoclopramide group reported an average 2.0-point decrease on LLS at 120 min. Conclusions Metoclopramide and ibuprofen may be effective alternative treatment options in HAH and AMS, especially for those patients who additionally report nausea.
Using Multiple Imputation with GEE with Non-monotone Missing Longitudinal Binary Outcomes.

This paper considers multiple imputation (MI) approaches for handling non-monotone missing longitudinal binary responses when estimating parameters of a marginal model using generalized estimating equations (GEE). GEE has been shown to yield consistent estimates of the regression parameters for a marginal model when data are missing completely at random (MCAR). However, when data are missing at random (MAR), the GEE estimates may not be consistent; the MI approaches proposed in this paper minimize bias under MAR. The first MI approach proposed is based on a multivariate normal distribution, but with the addition of pairwise products among the binary outcomes to the multivariate normal vector. Even though the multivariate normal does not impute 0 or 1 values for the missing binary responses, as discussed by Horton et al. (Am Stat 57:229–232, 2003), we suggest not rounding when filling in the missing binary data because it could increase bias. The second MI approach considered is the fully conditional specification (FCS) approach. In this approach, we specify a logistic regression model for each outcome given the outcomes at other time points and the covariates. Typically, one would only include main effects of the outcome at the other times as predictors in the FCS approach, but we explore if bias can be reduced by also including pairwise interactions of the outcomes at other time point in the FCS. In a study of asymptotic bias with non-monotone missing data, the proposed MI approaches are also compared to GEE without imputation. Finally, the proposed methods are illustrated using data from a longitudinal clinical trial comparing four psychosocial treatments from the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, where patients’ cocaine use is collected monthly for 6 months during treatment.
Abstract A21: Compound PIK3CA mutations support a mutational dose-response model for oncogene activation and response to PI3K inhibitor targeted therapy in breast cancer

PIK3CA mutations represent the most frequent oncogenic driver lesion found across all human cancers. Given that single PIK3CA mutations are a predictive biomarker for response to PI3K inhibition, and that these clinical benefits are small, we hypothesized that additional genomic factors may cooperate with single PIK3CA mutations in oncogenesis and response to PI3K inhibitors. We analyzed several large pan-cancer datasets and have discovered a phenomenon of dual PIK3CA mutations in 15% of all PIK3CA-mutant cancers, including breast cancer. Dual PIK3CA mutations are clonal, are found in both primary untreated and metastatic tumors, and are enriched at conserved amino acid positions. We have proved that the majority of dual PIK3CA mutations—including the most frequent dual PIK3CA mutant combinations in breast cancer—are in cis compound mutations (i.e., on the same allele, resulting in a protein molecule with two mutations) in patient samples and cell lines, as shown through multiple sequencing techniques including long-range single-molecule real-time sequencing (SMRT-seq). Compound PIK3CA mutations increase PI3K pathway signaling and growth proliferation in nontransformed cells and cancer cells in vitro and in vivo. Biochemical experiments using recombinant PI3K complexes reveal a mechanism where compound mutants increase PI3K complex thermal instability, resulting in increased kinase activity and liposome binding as compared to single mutants. Compound PIK3CA mutations render cells more sensitive to the PI3Kα inhibitors BYL719 and GDC-0077 than single PIK3CA mutations. These data translate to the clinic, where patients with dual PIK3CA-mutant metastatic breast cancer exhibit more durable responses to PI3K inhibition versus patients with single PIK3CA-mutant breast tumors. Our data support a novel mutational dose-response model for oncogene activation, where compound mutations amplify PI3K signaling and growth to a greater degree than single mutants, resulting in increased sensitivity to PI3Kα inhibitor targeted therapy. These findings also have therapeutic relevance, where compound PIK3CA mutations may be a superior predictive biomarker for response to PI3Kα inhibitors than single PIK3CA mutations, across PIK3CA-mutant cancers. Citation Format: Neil Vasan, Jared Johnson, Hong Shao, Pedram Razavi, Alexander Gorelick, Erik Ladewig, Alesia Antoine, Hardik Shah, Eneda Toska, Guotai Xu, Abiha Kazmi, Barry Taylor, Komal Jhaveri, Maura Dickler, Elisa de Stanchina, Eduard Reznik, Raul Rabadan, Melissa Smith, Robert Sebra, Lewis Cantley, Maurizio Scaltriti, Jose Baselga. Compound PIK3CA mutations support a mutational dose-response model for oncogene activation and response to PI3K inhibitor targeted therapy in breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A21.
Retire In-Home: A New Way to Use a Home to Guarantee Retirement Income

There is a growing retirement crisis and most of the focus has been on the fact that individuals are not saving enough for retirement, may not have access to pension schemes, and find it difficult to choose from a wide range of retirement products. One solution that has been considered is to improve access to Reverse Mortgages (RMs) so that individuals can convert their (possibly) single largest asset into a through-death income stream. However, current RMs are complex with constraints on who can use them, and with multiple parties to the transaction to hedge residual risks. As a result, a limited number of institutions (and that too with government support) offer such products. These challenges may have also limited the use of RMs for the typical individual saving for retirement and are unlikely to solve the larger crisis. We suggest a new approach - “Retire In-Home” (Retire through Income from one’s Home) - that leverages recently proposed tradeable instruments to improve retirement security and hedge against standard-of-living risks. These include a bond called BFFS/SeLFIES, designed to secure real retirement income for a fixed term (with potentially a second new bond, called a LIVE bond, designed to protect individuals against longevity risk if individuals do not want to purchase deferred annuities because of annuity challenges). Further, the paper also shows how a new investor segment could be tapped to expand financing for such transactions as recommended by Prof. Robert C. Merton. This paper demonstrates how Retire In-Home could simplify this market and allow even the most financially unsophisticated individual to participate in this transaction. The paper works through three cases: (a) when death is known (or a term income); (b) when longevity risk is hedged with deferred annuities; and (c) when longevity risk is hedged with LIVE Bonds. The paper concludes with extensions including accounting for up-front lumpsum payments, forward-starting contracts and even multi-occupant situations.
Improving Critical Care Documentation and Billing Amongst Pediatric Hospital Medicine Providers

Variability in billing and coding among physicians often exists due to a lack of physician knowledge regarding billing. Billing errors or omissions can lead to significant institutional financial repercussions. The aim of our project is to improve clinical documentation and billing practices for specific critical care diagnosis (sepsis, respiratory failure due to bronchiolitis and status asthmaticus) by 25% from July 2017-December 2017 among Pediatric Hospital Medicine (PHM) providers at a …
Structures of chaperone-associated assembly intermediates reveal coordinated mechanisms of proteasome biogenesis.

The proteasome mediates most selective protein degradation. Proteolysis occurs within the 20S core particle (CP), a barrel-shaped chamber with an α7β7β7α7 configuration. CP biogenesis proceeds through an ordered multistep pathway requiring five chaperones, Pba1–4 and Ump1. Using Saccharomyces cerevisiae, we report high-resolution structures of CP assembly intermediates by cryogenic-electron microscopy. The first structure corresponds to the 13S particle, which consists of a complete α-ring, partial β-ring (β2–4), Ump1 and Pba1/2. The second structure contains two additional subunits (β5–6) and represents a later pre-15S intermediate. These structures reveal the architecture and positions of Ump1 and β2/β5 propeptides, with important implications for their functions. Unexpectedly, Pba1’s N terminus extends through an open CP pore, accessing the CP interior to contact Ump1 and the β5 propeptide. These results reveal how the coordinated activity of Ump1, Pba1 and the active site propeptides orchestrate key aspects of CP assembly. Cryo-EM structures of assembly intermediates of the proteasome 20S core particle show how the coordinated activity of chaperones orchestrates early steps in proteasome biogenesis.