cssi/SciSciGPT-SciSciNet huggingface dataset:
Production and immunogenicity of multiple antigenic peptide (MAP) constructs derived from the S1 glycoprotein of infectious bronchitis virus (IBV)

Synthetic peptides were prepared as multiple antigenic peptide (MAP) constructs to the S1 glycoprotein of infectious bronchitis virus (IBV). The MAP system has been used in the production of anti-peptide and anti-protein antibodies. It has an advantage over linking peptides to a highly immunogenic carrier molecule because antibodies are not produced to the MAP core matrix of lysine residues. Two 25-residue peptides were synthesized to the Arkansas serotype and two were synthesized to the Massachusetts serotype of IBV. The peptide sequences correspond to amino acid residues 64 to 88 and to residues 117 to 141 for each of the IBV serotypes. A MAP construct for each peptide was prepared by linking 4 copies of a peptide to the immunogenetically inert core matrix of lysine residues. The MAP constructs were used to immunize specific pathogen free chickens. Anti-peptide ELISA titers and the dot immunobinding assay against the homologous peptide were positive for all of the sera tested whereas the anti-whole virus ELISA titers and virus neutralization titers were negative for all of the sera tested. Hyperimmune sera against whole virus did not cross react with synthetic peptides made to the heterologous virus suggesting a possible role for the MAP constructs in a serotype specific dot blot or ELISA test for IBV.
Non-violence as respect for all suffering: Thoughts inspired by Eyad El Sarraj

This paper, first presented at a memorial conference for the Palestinian psychiatrist and activist Eyad el-Sarraj, examines the connection between non-violence and acknowledgement of injuries and trauma in the Israel-Palestine context. It explores the complexity of mutual recognition in a situation of actual oppression, suggesting the counter-intuitive value of the victim’s power to humanize the perpetrator. It develops the idea of the third, the witness and the framing opposition ‘only one can live’ versus ‘every life matters,’ drawing on Primo Levi’s evocation of ‘the drowned and the saved’ and placing the issue of dignifying suffering alongside recognition of the ‘monstrousness’ in each subject and in relation to the productivity of the ethos of ‘Ubuntu.’
Creation of an Ileocolic Bladder after Cystectomy

AbstractA divided segment of ileum and colon is used to create a neobladder after cystectomy with a cecourethral anastomosis to provide volitional voiding with continence. Such a bladder provides for good sensation with a large low pressure reservoir and an antireflux ureteral anastomosis. The standard nerve-sparing cystoprostatectomy is performed and no segment of the bladder or prostate is left to compromise the cancer operation. In female or male patients with diffuse carcinoma in situ a similar reservoir with a plicated ileocutaneous anastomosis also can provide continence with intermittent catheterization. Four patients with a urethral anastomosis have day and nighttime continence, and 2 with a cutaneous stoma have 4 to 5-hour dry intervals. Ultimately, it is possible for a patient to void with good urinary control and to have sexual function after cystectomy.
Molecular Dynamics Simulations of Protein Folding

I illustrate the use of the replica exchange molecular dynamics (REMD) algorithm to study the folding of a small (57 amino acids) protein that folds into a three-helix bundle, protein A. The REMD is a trivially parallel method that uses multiple copies of the system of interest to study the canonical ensemble equilibrium properties. Each replica represents a different thermodynamic state, usually at different temperatures. This method enhances the configurational sampling of proteins and allows us to study folding in simulations that are much shorter than the folding timescale for the system at ambient temperature. I show that using REMD and the Amber force field, I can obtain stable configurations of protein A whose backbone root mean square distance (RMSD) is within 0.17 nm of the nuclear magnetic resonance (NMR)-determined structure without biasing the system toward the folded structure. The simulations are done in explicit solvent and starting from nearly extended configurations. This calculation shows that currently available force fields and enhanced sampling methods perform reasonably well in describing the folded structure of small proteins.
P-003 development of an endovascular magnetic filter device to enable high dose intra-arterial chemotherapy: finite element modeling

Purpose A temporary endovascular magnetic filter was developed to remove iron oxide particles conjugated to chemotherapeutics from the blood, preventing chemotherapeutics from circulating where it is not needed to reduce systemic toxicity and enable higher dose therapy. Magnetically targeted drug delivery through filtration could play an important role in expanding intra-arterial therapy to head and neck cancer. Previous proof-of-concept established rapid high-capacity binding of iron oxide particles in swine serum in vitro , and preliminary demonstration of qualitative efficacy in vivo in a porcine model. In this study, we aim to optimize the filtration efficacy of the prototype through finite element magnetic modeling. Method Magnetic modeling was performed in 2D using Finite Element Method Magnetics (FEMM) software (Brighton, MA). Prototype designs consisting of individual neodymium N52 magnets were simulated to optimize the following parameters: i) magnetization across length vs diameter, ii) magnet orientations aligned or reversed, iii) magnet spacing, and iv) magnet length. The average magnetic flux gradient (∇By) was computed across a unit length consisting of one magnet and adjoining gap space as shown in [Figure 1A][1]. ∇By is directly correlated to the magnetic force on an iron particle, and was plotted as against D, distance from the surface of the magnet. Designs with greater ∇By at high D were considered more effective. Results Designs with magnetization across the length and reversed (like polarities facing and repelling each other), had slightly higher ∇By than designs with magnetization across the diameter and aligned (opposite polarities facing and attracting each other). Magnetization across the length and aligned, and magnetization across the diameter and reversed both had low ∇By at high D. For designs with magnetization across the length and reversed orientations as shown in [Figure 1B][1], reduced spacing between magnets increased ∇By. Reduced magnet length increased ∇By at low D, at the expense of ∇By at high D. Conclusions The current endovascular magnetic filter prototype could be improved by using longer magnets magnetized across the length in the reversed orientation with like polarities repelling each other and minimal spacing between magnets. ![Abstract P-003 Figure 1][2] Abstract P-003 Figure 1 Disclosures C. Sze: 1; C; NIH NCI. 5; C; ChemoFilter. M. Mabray: None. P. Lillaney: None. S. Kondapavulur: None. D. Liu: None. M. Wilson: 1; C; NIH NCI. 6; C; Penumbra. S. Hetts: 1; C; NIH NCI. 6; C; Penumbra. [1]: #F1 [2]: pending:yes
Ultrafast time-resolved photon-number statistics

Optical homodyne tomography1 (OHT) has previously been used to determine the quantum state of fields,2 and thus the photon-number statistics3 of these fields in the 300-ps regime. We have demonstrated the use of OHT to measure the time-resolved photon-number statistics of a 5-ns pulsed field with a sampling time of 130 fs and time resolution of 60 ps. The ultrafast sampling allows us to measure the statistics of very-broadband fields, such as that of a diode laser below threshold.
An Exploration of the Associations of Alcohol-Related Social Media Use and Message Interpretation Outcomes to Problem Drinking Among College Students

ABSTRACTCollege students’ use of digital communication technology has led to a rapid expansion of digital alcohol marketing efforts. Two surveys (total usable n = 637) were conducted to explore college students’ experiences with alcohol-related social media, their decision making related to alcohol use, and their problematic drinking behaviors. Study results indicated that students’ use of alcohol-related social media predicted their problem drinking behaviors. In addition, students’ wishful identification, perceived desirability, perceived similarity, and normative beliefs predicted their expectancies for drinking alcohol. Finally, students’ expectancies for drinking alcohol predicted their problematic drinking behaviors.
Surgery for Benign Thyroid Disease Causing Tracheoesophageal Compression

Even though the incidence of multinodular goiter is decreasing in the United States, still we see a large number of neglected goiters causing pressure effects on the surrounding structures. Both tracheal and esophageal displacement cause compression symptoms. However, tracheal compression may lead to acute airway distress. Eighteen per cent of our patients presented with acute airway problems, requiring emergency admission or intubation. Surgical intervention has been our preferred approach whenever there are signs or symptoms of tracheoesophageal compression. Fifty-five per cent of patients had only tracheal compression, while 18 per cent had only esophageal compression. Twenty-seven per cent had compression of both trachea and esophagus. Eighty-five per cent of patients had some symptoms of compression, while only 15% were asymptomatic despite large goiters. Compression symptoms and acute problems were noticed more frequently in patients with substernal goiters. Our preoperative work-up regularly included complete history, physical examination, indirect laryngoscopy, and airway radiography. Barium studies were performed if patients had dysphagia. Computed tomography scans were utilized if there was mediastinal extension. Pulmonary flow volume studies were used to locate the site of compression. However, decisions relative to surgical intervention were based primarily on clinical judgment. Since the postoperative morbidity is minimal in surgery for thyroid abnormalities, we strongly recommend early surgical intervention in patients with tracheoesophageal compression caused by enlarged thyroids.
Biocontrol of Spider Mites in California Strawberry Production

Field experiments were conducted in 2013 and 2014 to evaluate the predation efficacy of four commercially available predatory mites (Phytoseiidae): Phytoseiulus persimilis, Neoseiulus californicus,...
Atmospheric Radiative Transfer and Climate

In this chapter, the basics of radiative transfer through the atmosphere are introduced. The key role of trace constituents such as water vapor, carbon dioxide, and ozone are explained. The physics behind the selective absorption of longwave frequencies by polyatomic molecules is introduced. The radiative transfer equation is derived and simplified to obtain an understanding of radiative equilibrium. The effect of clouds on radiative transfer through the atmosphere is described, including the influence of water content and particle radius. The concept of radiative–convective equilibrium is developed and a sophisticated model is used to show the dependence of the vertical profile of temperature on key trace gases that absorb solar or terrestrial radiation. The radiative–convective equilibrium model is used to show the effect of different cloud types on the energy balance and surface temperature of Earth. The cloud radiative effect is defined and observations of it shown, along with observed distributions of different cloud types.
Using Family-Based Exposure With Response Prevention to Treat Obsessive-Compulsive Disorder in Young Children: A Case Study

Cognitive-behavioral therapy (CBT) using exposure with response prevention (ERP) is the treatment of choice for obsessive-compulsive disorder (OCD); however, developmental modifications should be considered when treating young children. This article presents a case study illustrating family-based CBT using ERP with a 7-year-old boy. The delivery of ERP for this case was guided by 3 main principles: (a) family involvement with a focus on reducing family accommodation, (b) understanding the functional relation between the client's obsessions and compulsions, and (c) creating conditions to facilitate habituation during exposure. Outcomes for this case indicate significant improvement in functioning and OCD symptoms. Results highlight the importance of family involvement and the applicability of using a function-based habituation framework when delivering ERP to this unique population.
Defective signaling, osteoblastogenesis and bone remodeling in a mouse model of connexin 43 C-terminal truncation

In skeletal tissue, loss or mutation of the gap junction protein connexin 43 (Cx43, also known as GJA1) in cells of the osteoblast lineage leads to a profound cortical bone phenotype and defective tissue remodeling. There is mounting evidence in bone cells that the C-terminus (CT) of Cx43 is a docking platform for signaling effectors and is required for efficient downstream signaling. Here, we examined this function, using a mouse model of Cx43 CT-truncation (Gja1 K258Stop). Relative to Gja1+/- controls, male Gja1-/K258Stop mice have a cortical bone phenotype that is remarkably similar to those reported for deletion of the entire Cx43 gene in osteoblasts. Furthermore, we show that the Cx43 CT binds several signaling proteins that are required for optimal osteoblast function, including PKCδ, ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1, respectively) and β-catenin. Deletion of the Cx43 CT domain affects these signaling cascades, impacting osteoblast proliferation, differentiation, and collagen processing and organization. These data imply that, at least in bone, Cx43 gap junctions not only exchange signals, but also recruit the appropriate effector molecules to the Cx43 CT in order to efficiently activate signaling cascades that affect cell function and bone acquisition.
Enhanced mechanical properties of W1−yMoyO3 nanocomposite thin films

We report on the enhanced mechanical properties of ∼60 nm thick W-Mo-O nanocomposite films, which are of current interest as structural and electrode materials in photo-related energy technologies. W-Mo-O films were sputter-deposited onto Si(100) by varying the growth temperature (Ts) ranging from 25 to 500 °C. The molybdenum (Mo) content in the films was varied in the range of y = 0.05–0.15 by employing the W-Mo target with a variable Mo content. Structural and mechanical characterization was performed to understand the combined effect of the Mo content and Ts on the structure and mechanical behavior of W-Mo-O films. The results indicate that the effect of Ts is significant on the growth and microstructure of W-Mo-O films. The effect of the Mo-content is reflected in elevating the Ts needed for film crystallization coupled with the average grain-size reduction. Structural studies revealed that the W-Mo-O films were amorphous for Ts ≤ 300 °C, at which point amorphous-to-crystalline transformation occurs. ...
The Final Problem: Constructing Coherence in the Holmesian Canon

The death and resurrection of Sherlock Holmes, a contrarian reading in which Holmes helps the murderer, and the century-long tradition of the Holmesian Great Game with its pseudo-scholarly readings in light of an ironic conviction that Holmes is real and Arthur Conan Doyle merely John Watson’s literary agent. This paper relies on these events in the afterlife of Sherlock Holmes in order to trace an outline of the author function as it applies to the particular case of Doyle as the author of the Sherlock Holmes stories. The operations of the author function can be hard to identify in the encounter with the apparently natural unity of the individual work, but these disturbances at the edges of the function make its effects more readily apparent. This article takes as its starting point the apparently strong author figure of the Holmesian Great Game, in which “the canon” is delineated from “apocrypha” in pseudo-religious vocabulary. It argues that while readers willingly discard provisional readings in the face of an incompatible authorial text, the sanctioning authority of the author functions merely as a boundary for interpretation, not as a personal-biographical control over the interpretation itself. On the contrary, the consciously “writerly” reading of the text serves to reinforce the reliance on the text as it is encountered.The clear separation of canon from apocrypha, with the attendant reinforced author function, may have laid the ground not only for the acceptance of contrarian reading, but also for the creation of apocryphal writings like pastiche and fan fiction.
Abstract 391: Endogenous Drp1 Modulates Cardiac Respiration Through mPTP and Independent of Fission

Background: The cardiac mitochondria exhibit a stable morphology with a rather low level of dynamic changes. However, fission and fusion proteins, such as dynamin-related protein 1 (DRP1) are abundant in the heart. Whether these proteins bear other functions in the heart than mitochondrial dynamics regulation are largely unknown. We hypothesize that endogenous DRP1 in the heart regulates mitochondrial respiration independent of fission. Methods: Mitochondrial respiration was determined by measuring the OCR with Seahorse assay or Clark type electrode in adult rat cardiomyocytes or mitochondria isolated from adult mouse heart. Confocal imaging was used to quantify mitochondrial morphology in adult cardiomyocytes and H9C2 myoblasts. To evaluate the role of mitochondrial permeability transition pore (mPTP), we monitored superoxide flashes (SOF) and laser-induced mPTP openings, and used cyclophilin D knockout mice (CypD KO). Mitochondrial ROS and Ca2+ were also monitored. Results: Inhibiting the DRP1 GTPase activity by Mdivi-1 or overexpression of the dominant-negative mutant (DRP1-K38A) induced mild mitochondrial morphological changes in adult cardiomyocytes, and inhibited mitochondrial respiration. Modulation of fission/fusion by overexpressing DRP1 or treating cells with S3, a compound facilitates fusion, exhibited significant morphological changes, but failed to influence respiration. Therefore, endogenous DRP1 activity may regulate respiration in the heart and this effect is dissociated with morphological changes. Further, inhibiting DRP1 activity attenuated the frequency of SOF, indicating decreased transient mPTP openings, delayed laser-induced permanent mPTP opening, and increased mitochondrial Ca2+. Inhibiting DRP1 activity decreased mitochondrial ROS levels. The role of DRP1 inhibition on respiration absents in CypD KO myocytes, suggesting the involvement of mPTP in the modulation of respiration by endogenous DRP1. Conclusion: These results suggest that endogenous DRP1 positively regulates respiration in the heart. This effect is likely independent of its role in mitochondrial fission. DRP1 regulation of respiration may involve transient opening of mPTP and contribute to mitochondrial Ca2+ and ROS signaling.
Nitrogen-Doped Three-Dimensional Graphene-Supported Palladium Nanocomposites: High-Performance Cathode Catalysts for Oxygen Reduction Reactions

This study reports an effective strategy for fabricating three-dimensional nitrogen-doped graphene supports for palladium nanoparticles (Pd–N/3D-GNS) and studying the electrochemical activity of the synthesized nanocomposites toward oxygen electroreduction in alkaline media as well as implementing the nanocomposite as cathode catalysts in anion exchange membrane fuel cells (AEMFC). It was demonstrated that by embedding and etching an amorphous sacrificial silica template into the reduced graphene matrix, the as-prepared nanocomposites pyrolyzed into hierarchically porous 3D-nanosheets composed of interconnected nitrogen-doped graphene nanostacks, which was confirmed using transmission electron microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Palladium nanoparticles were then deposited on the N/3D-GNS supports using a surfactant-free technique and characterized using various surface analysis and potentiodynamic techniques. By analyzing the linear sweep voltammograms obtained ...
Student assessed integrated learning: SAILing to a holistic design of holistic engineering education

This Work-in-Progress paper presents a framework for students' holistic learning, growth, and development recently created at and for Northeastern University. The Student Assessed Integrated Learning (SAIL) initiative was introduced for the first time to 179 first-year students who had not designated their major prior to entering the University. Our preliminary data indicate that most students felt the SAIL framework informed how they viewed their past experiences and helped them to shape their academic, personal, and/or professional goals. Further data collection and analyses to investigate the SAIL framework's effectiveness in helping students articulate and shape holistic learning is ongoing.
Model evaluation of rapid 4-dimensional lung tomosynthesis.

Abstract Purpose This is an investigation of a lung motion digital tomosynthesis (DTS) model using combined stationary detector and stationary cold cathode x-ray sources at projection acquisition rates that exceed the present norms. The intent is to reduce anatomical uncertainties from artifacts inherent in thoracic 4-dimensional computed tomography (CT). Methods and materials Parameters necessary to perform rapid lung 4-dimensional DTS were studied using a conventional radiographic system with linear motion of the x-ray source and a simple hypothetical hardware performance model. Hypothetical rapid imaging parameters of sweep duration, projections per second, pulse duration, and tube current (mA) were derived on the basis of 0.5 mm and 1 mm motion captures per phase, 10 and 15 breaths per minute (bpm), 10 to 40 mm breathing amplitude, and 2 signal-to-noise ratio (SNR) levels. Anterior-posterior and lateral projection images of a normal size anthropomorphic thorax phantom with iodine contrast inserts were collected and reconstructed with an algebraic algorithm to study the effects of reduced x-ray output associated with field emission cold cathodes composed of carbon nanotubes or metal Spindt-type. Radiographic projections were collected at 3 SNR levels that were set at standard clinical DTS milliampere-seconds (mAs) and reduced corresponding to 50% and 25% standard DTS mAs to simulate a reduced x-ray output. Results The DTS SNR of the inserts was superior in all reconstructions at clinical mAs versus automatic exposure-control radiographs and superior in 3 of 4 at the 50% and 25% mAs levels. The most demanding performance parameters corresponding to 40 mm amplitude, 15 bpm, 0.5 mm motion capture limit, and 61 projections were sweep duration (10.4 msec), projection rate (5862 projections per second), pulse duration (0.161 msec), current 189 mA anterior-posterior, and 653 mA lateral. Conclusions Feasibility depends on the output performance of stationary cold cathode hardware being developed for DTS. Present image receptor technology can accommodate frame acquisition rates.
Innate Immune Signaling in Drosophila Blocks Insulin Signaling by Uncoupling PI(3,4,5)P3 Production and Akt Activation

In obese adipose tissue, Toll-like receptor signaling in macrophages leads to insulin resistance in adipocytes. Similarly, Toll signaling in the Drosophila larval fat body blocks insulin-dependent growth and nutrient storage. We find that Toll acts cell autonomously to block growth but not PI(3,4,5)P3 production in fat body cells expressing constitutively active PI3K. Fat body Toll signaling blocks whole-animal growth in rictor mutants lacking TORC2 activity, but not in larvae lacking Pdk1. Phosphorylation of Akt on the Pdk1 site, Thr342, is significantly reduced by Toll signaling, and expression of mutant AktT342D rescues cell and animal growth, nutrient storage, and viability in animals with active Toll signaling. Altogether, these data show that innate immune signaling blocks insulin signaling at a more distal level than previously appreciated, and they suggest that manipulations affecting the Pdk1 arm of the pathway may have profound effects on insulin sensitivity in inflamed tissues.
A modular approach for high-flux lactic acid production from methane in an industrial medium using engineered Methylomicrobium buryatense 5GB1.

Convergence of market drivers such as abundant availability of inexpensive natural gas and increasing awareness of its global warming effects have created new opportunities for the development of small-scale gas-to-liquid (GTL) conversion technologies that can efficiently utilize methane, the primary component of natural gas. Leveraging the unique ability of methanotrophs that use methane as carbon and energy source, biological GTL platforms can be envisioned that are readily deployable at remote petroleum drilling sites where large chemical GTL infrastructure is uneconomical to set-up. Methylomicrobium buryatense, an obligate methanotroph, has gained traction as a potential industrial methanotrophic host because of availability of genetic tools and recent advances in its metabolic engineering. However, progress is impeded by low strain performance and lack of an industrial medium. In this study, we first established a small-scale cultivation platform using Hungate tubes for growth of M. buryatense at medium-to-high-throughput that also enabled 2X faster growth compared to that obtained in traditional glass serum bottles. Then, employing a synthetic biology approach we engineered M. buryatense with varying promoter (inducible and constitutive) and ribosome-binding site combinations, and obtained a strain capable of producing l-lactate from methane at a flux 14-fold higher than previously reported. Finally, we demonstrated l-lactate production in an industrial medium by replacing nitrate with less-expensive ammonium as the nitrogen source. Under these conditions, l-lactate was synthesized at a flux approximately 50-fold higher than that reported previously in a bioreactor system while achieving a titer of 0.6 g/L. These findings position M. buryatense closer to becoming an industrial host strain of choice, and pave new avenues for accelerating methane-to-chemical conversion using synthetic biology.
Pharmacokinetics of High-Dose Propylene Glycol–Free Melphalan in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation

Abstract High-dose melphalan followed by autologous stem cell transplant (ASCT) is standard of care for eligible patients with multiple myeloma (MM). Evomela (propylene glycol–free melphalan HCl [PG-Free Mel]; Spectrum Pharmaceuticals, Irvine, CA) was approved by the US Food and Drug Administration as conditioning therapy for ASCT in MM in 2 daily 100-mg/m2 doses for a total dose of 200 mg/m2. In this phase II, open-label study PG-Free Mel (Evomela) conditioning was given at single dose of 200 mg/m2 on day −2 pre-ASCT to establish pharmacokinetic (PK) parameters and safety. Twenty-four patients (median age, 64 years) were enrolled between August 2016 and February 2017. Myeloablation followed by successful neutrophil engraftment occurred at a median of 10 days in all patients. Peak melphalan concentration was observed at 10 minutes after infusion, whereas there was considerable variation in the maximum plasma concentration (Cmax) and area under concentration time curve (AUC). Median Cmax was 7380 ng/mL (interquartile range [IQR], 6522 to 8027). Similarly, median AUC was 533,552 ng/mL∙min (IQR, 450,850 to 662,936). PG-Free Mel had an acceptable safety profile regardless of the exposure, with no mortality and an overall response rate of 96% and a very good partial response rate of 75%. In conclusion, although PG-Free Mel at a single dose of 200 mg/m2 was safe, considerable PK variability was observed with the highest quartile having an ~3-fold higher AUC than the first quartile, suggesting that strategies for higher targeted exposure could be explored in future trials to optimize clinical benefit.
Apolipoprotein B or Low-Density Lipoprotein Cholesterol: Is It Time for a Twenty-First-Century Lipid Marker?

The success of LDL cholesterol (LDL-C)2 as a risk marker and therapeutic target of cardiovascular disease is indisputable. However, new data suggest that apolipoprotein B (apoB) is a more relevant measure of lipid burden and heart disease risk. A recent analysis of the National Health and Nutrition Examination Survey (NHANES) compared apoB concentrations among individuals with similar LDL-C concentrations. The data show that patients with the highest concentrations of apoB were significantly more likely to have a cardiac event within 15 years (1). Despite accumulating evidence in favor of apoB, guidelines continue to focus solely on LDL-C. When comparing the 2 biomarkers, it is important to note that LDL-C is not a specific molecule, nor has it been consistently defined or measured. The origin and historical definition of LDL-C dates back to the renowned Framingham Heart …
The Power of Your Beliefs

I believe that women can be taught to use money as a powerful tool to live meaningful lives and to change the world. I also believe that female leaders must advocate and support all women in finance. I believe women with this power can create amazing results. This is my “why.” It is the reason for this book and it is the belief that supports my values and my vision which I discuss in Chapter 10.
Fluid replacement in burned patients.

The selection of the appropriate fluid replacement and of the manner of fluid delivery is dependent on a sound understanding of the pathophysiology of burn injury. The local and generalized fluid and protein shifts that occur dictate the type of fluid and the necessary monitoring techniques. Those caring for the burned patient must remain both flexible and knowledgeable in order to optimize results.
Preparation of Ultrafine Particles of Metal Oxides

Ultrafine particles of 0.01–10 µ and their preparation form the basis for a wide range of inorganic compounds which are utilized extensively in such fields as protective coatings, electronics, ceramics, paper, plastics, building materials, etc. Historically, the pigment industry has been a pioneer in this field extending their fine particle technology and products into many areas, other than coatings.
Dissection, Optimization, and Structural Analysis of a Covalent Irreversible DDAH1 Inhibitor.

Inhibitors of the human enzyme dimethylarginine dimethylaminohydrolase-1 (DDAH1) can control endogenous nitric oxide production. A time-dependent covalent inactivator of DDAH1, N5-(1-imino-2-chloroethyl)-l-ornithine (KI = 1.3 μM, kinact = 0.34 min–1), was conceptually dissected into two fragments and each characterized separately: l-norvaline (Ki = 470 μM) and 2-chloroacetamidine (KI = 310 μM, kinact = 4.0 min–1). This analysis suggested that the two fragments were not linked in a manner that allows either to reach full affinity or reactivity, prompting the synthesis and characterization of three analogues: two that mimic the dimethylation status of the substrate, N5-(1-imino-2-chloroisopropyl)-l-ornithine (kinact/KI = 208 M–1 s–1) and N5-(1-imino-2-chlorisopropyl)-l-lysine (kinact/KI = 440 M–1 s–1), and one that lengthens the linker beyond that found in the substrate, N5-(1-imino-2-chloroethyl)-l-lysine (Cl-NIL, KI = 0.19 μM, kinact = 0.22 min–1). Cl-NIL is one of the most potent inhibitors reported for ...
Use of user-centered design to create a smartphone application for patient-reported outcomes in atopic dermatitis

The ubiquity and convenience of smartphones carries great potential for collecting patient-reported data to address many gaps in research, especially those that rely on ongoing, real-time data collection. Health care apps have often suffered from low utility due to lack of consideration of the needs of multiple stakeholders. We employed an iterative user-centered design approach to create the myEczema smartphone application (app) to study the burden of disease of atopic dermatitis. We outline below the steps we took for developing myEczema for multiple stakeholders, including patients, clinicians, and researchers.
Prospective validation of the Parkland Grading Scale for Cholecystitis

Abstract Background The Parkland Grading Scale for Cholecystitis (PGS) was developed as an intraoperative grading scale to stratify gallbladder (GB) disease severity during laparoscopic cholecystectomy (LC). We aimed to prospectively validate this scale as a measure of LC outcomes. Methods Eleven surgeons took pictures of and prospectively graded the initial view of 317 GBs using PGS while performing LC (LIVE) between 9/2016 and 3/2017. Three independent surgeon raters retrospectively graded these saved GB images (STORED). The Intraclass Correlation Coefficient (ICC) statistic assessed rater reliability. Fisher's Exact, Jonckheere-Terpstra, or ANOVA tested association between peri-operative data and gallbladder grade. Results ICC between LIVE and STORED PGS grades demonstrated excellent reliability (ICC = 0.8210). Diagnosis of acute cholecystitis, difficulty of surgery, incidence of partial and open cholecystectomy rates, pre-op WBC, length of operation, and bile leak rates all significantly increased with increasing grade. Conclusions PGS is a highly reliable, simple, operative based scale that can accurately predict outcomes after LC. Table of contents summary The Parkland Grading Scale for Cholecystitis was found to be a reliable and accurate predictor of laparoscopic cholecystectomy outcomes. Diagnosis of acute cholecystitis, surgical difficulty, incidence of partial and open cholecystectomy rates, pre-op WBC, operation length, and bile leak rates all significantly increased with increasing grade.
Sphingosine Kinase Activates the Mitochondrial Unfolded Protein Response and Is Targeted to Mitochondria by Stress

Summary The mitochondrial unfolded protein response (UPRmt) is critical for maintaining mitochondrial protein homeostasis in response to mitochondrial stress, but early steps in UPRmt activation are not well understood. Here, we report a function for SPHK-1 sphingosine kinase in activating the UPRmt in C. elegans. Genetic deficiency of sphk-1 in the intestine inhibits UPRmt activation, whereas selective SPHK-1 intestinal overexpression is sufficient to activate the UPRmt. Acute mitochondrial stress leads to rapid, reversible localization of SPHK-1::GFP fusion proteins with mitochondrial membranes before UPRmt activation. SPHK-1 variants lacking kinase activity or mitochondrial targeting fail to rescue the stress-induced UPRmt activation defects of sphk-1 mutants. Activation of the UPRmt by the nervous system requires sphk-1 and elicits SPHK-1 mitochondrial association in the intestine. We propose that stress-regulated mitochondrial recruitment of SPHK-1 and subsequent S1P production are critical early events for both cell autonomous and cell non-autonomous UPRmt activation.
The Constitutionality of Immigration Sanctuaries and Anti-Sanctuaries: Originalism, Current Doctrine, and a Second-Best Alternative

The Supreme Court’s immigration jurisprudence is fundamentally misguided, in the sense that it has little basis in the original meaning of the Constitution. In this essay, I will explain why I think so, and what the Court might do to ameliorate the effects of its past mistakes without overruling a raft of settled precedents. Part I analyzes the text of the Constitution, which offers a reasonably clear allocation of authority over immigration between the state and federal governments. The Foreign Commerce Clause empowers Congress to limit the entry of aliens onto American soil, and the Naturalization Clause authorizes Congress to set uniform criteria for admission to American citizenship. Nothing on the face of the Constitution permits Congress to displace the states’ residual authority over aliens, which includes the power to exclude or expel unsuitable persons from their own territory. Part II reviews early debates in Congress about the scope and nature of federal power over immigration. There were important disagreements, some of which resemble today’s policy debates, but Congress generally refrained from going much beyond what the text of the Constitution pretty clearly authorizes. Part III traces the evolution of Supreme Court doctrine. The Court began by rooting federal immigration authority primarily in the Foreign Commerce Clause, where it belongs, but then misinterpreted that Clause. In the late nineteenth century, the Justices made a dramatic and largely unexplained shift to a non-textual theory under which broad federal authority over immigration and aliens is treated as an inherent aspect of American sovereignty. Part IV shows that this doctrinal shift may not have had much practical significance. In non-immigration contexts, the Court eventually interpreted the Commerce Clause itself in a way that gave Congress practically the same far-reaching authority that the inherent power theory bestows in the immigration field. Thus, even if the Court had stuck with the Foreign Commerce Clause as the primary source of federal authority over immigration, the result would likely have been much the same as what the Court has mistakenly put in its place. Part V assumes that the Court is very unlikely to reconsider the well-established inherent power theory. In recent decades, however, the Justices have been experimenting with doctrinal devices designed to put some limits on the almost unlimited Commerce Clause authority that previous cases had mistakenly conferred on Congress. The paper concludes with two examples showing how these limiting doctrines can and should be used to resolve recent controversies in which some states have desired to pursue policy objectives to which federal officials object.
Abstract TP502: Childhood Cerebral Arteriopathy in Glycogen Storage Disease Type 1

Introduction: Glycogen storage disease type 1 (GSD1) is a rare genetic metabolic disorder caused by defects of glucose-6-phosphatase complex, resulting in a wide array of manifestations such as hep...
Rural-urban disparities in tobacco retail access in the southeastern United States: CVS vs. the dollar stores.

Abstract Objectives CVS, the largest US pharmacy chain, discontinued selling tobacco products in 2014; meanwhile, Family Dollar and Dollar General, the two largest dollar store chains, began selling tobacco in 2012 and 2013, respectively. The purpose of this study is to evaluate the differential change in tobacco retailer density (TRD) by rurality throughout 12 Southeastern US states. Methods Tobacco retailer density was calculated for CVS and dollar store locations and combined to represent retailer density change before and after policy changes. Bivariate analyses were conducted to compare the corporate-initiated changes in county-level retailer density across rurality categories. Results Findings suggest a statistically significant difference (p Conclusions Recent corporate policy changes on tobacco sales have increased access to tobacco retailers in rural counties considerably more than in urban counties, contributing to further disparities. CVS pharmacies discontinuing tobacco sales caused a decrease in retail density in urban areas, and the decision of the dollar stores locations initiating tobacco sales resulted in a greater burden to rural and small-metro counties.
Ultrafast and accurate 16S rRNA microbial community analysis using Kraken 2

For decades, 16S ribosomal RNA sequencing has been the primary means for identifying the bacterial species present in a sample with unknown composition. One of the most widely used tools for this purpose today is the QIIME (Quantitative Insights Into Microbial Ecology) package. Recent results have shown that the newest release, QIIME 2, has higher accuracy than QIIME, MAPseq, and mothur when classifying bacterial genera from simulated human gut, ocean, and soil metagenomes, although QIIME 2 also proved to be the most computationally expensive. Kraken, first released in 2014, has been shown to provide exceptionally fast and accurate classification for shotgun metagenomics sequencing projects. Bracken, released in 2016, then provided users with the ability to accurately estimate species or genus relative abundances using Kraken classification results. Kraken 2, which matches the accuracy and speed of Kraken 1, now supports 16S rRNA databases, allowing for direct comparisons to QIIME and similar systems. For a comprehensive assessment of each tool, we compare the computational resources and speed of QIIME 2’s q2-feature-classifier, Kraken 2, and Bracken in generating the three main 16S rRNA databases: Greengenes, SILVA, and RDP. For an evaluation of accuracy, we evaluated each tool using the same simulated 16S rRNA reads from human gut, ocean, and soil metagenomes that were previously used to compare QIIME, MAPseq, mothur, and QIIME 2. We evaluated accuracy based on the accuracy of the final genera read counts assigned by each tool. Finally, as Kraken 2 is the only tool providing per-read taxonomic assignments, we evaluate the sensitivity and precision of Kraken 2’s per-read classifications. For both the Greengenes and SILVA database, Kraken 2 and Bracken are up to 100 times faster at database generation. For classification, using the same data as previous studies, Kraken 2 and Bracken are up to 300 times faster, use 100x less RAM, and generate results that more accurate at 16S rRNA profiling than QIIME 2’s q2-feature-classifier. Kraken 2 and Bracken provide a very fast, efficient, and accurate solution for 16S rRNA metataxonomic data analysis.
A Rare Case of Pancytopenia Post Heart Transplant

Introduction Hematologic malignancy following solid organ transplant is uncommon and no cases have been reported in heart transplant recipients. We present a case of acute promyelocytic leukemia (APL) after orthotopic heart transplant. Case Report 57 year-old, with dilated cardiomyopathy secondary to sarcoidosis and no history of malignancy underwent successful orthotopic heart transplant. He had one episode of cell mediated rejection which was treated with pulse dose steroids. He was on tacrolimus, cellcept and prednisone for maintenance immunosuppression. Ten months post-transplant, routine laboratory test revealed pancytopenia which was attributed to medication side effects. His cellcept and valcyte were discontinued. He received Filgrastim. Cytomegalovirus, Epstein-Barr virus, and Parvovirus B-19 infections were ruled out. He had recurrent episodes of decline in his absolute neutrophil counts and was referred to hematology. A bone marrow aspirate and smear showed left shift granulocytic maturation arrest in a promyelocytic/myelocytic stage and cells suggestive of Auer rod. FISH cytogenetics, with 23% positive for PML-RARA fusion gene, confirmed the diagnosis of APL. He was initiated on therapy with All-trans retinoic acid (ATRA). Treatment with arsenic trioxide was deferred due to concerns for cardiotoxicity. His treatment course was also remarkable for differentiation syndrome which responded to hydroxyurea and dexamethasone. Overall, he had good response to ATRA and repeat BMB showed normocellular marrow with trilineage hematopoiesis with no evidence of APL. Summary Clinicians should maintain a high degree of suspicion when patients with a history of OHT develop unexplained pancytopenia. A small case series revealed the population most commonly affected with post-transplant APL were males, with a median age of 50 years at diagnosis and within a median interval of two years post solid organ transplant. Our patient was able to achieve remission without the standard chemotherapeutic agents used to treat APL associated with cardiotoxicity such as arsenic trioxide and anthracycline. To our knowledge, this case is the first reported of post orthotopic heart transplant acute promyelocytic leukemia.
Parental Ethnic Identity and Its Influence on Children's Oral Health in American Indian Families.

Objectives: To examine the relationship between ethnic identity and oral health knowledge, beliefs, behavior, and outcomes in American Indian families. Methods: Secondary data were analyzed for 579 parent–child dyads in a randomized controlled trial aimed at reducing early childhood caries in a Northern Plains tribal community. Data included demographic characteristics; parental ethnic identity; oral health knowledge, beliefs, and behavior; and parental/pediatric oral health outcomes. Ethnic identity was assessed using two measures: perceived importance of tribal identity and tribal language proficiency. We examined the association of baseline ethnic identity with baseline and longitudinal oral health measures. Results: At baseline, importance of tribal identity was significantly associated with several oral health beliefs, and one’s locus of control measure (external-chance). Baseline scores on importance of tribal identity were also associated with one’s oral heath belief (perceived severity), the same locus of control measure, and oral health knowledge and behavior over the three years of study follow up. Tribal language proficiency was not associated with any study measures at baseline, although it was associated with parental oral health status over the three years. Conclusions: Ethnic identity was associated with a range of oral health constructs expected to influence American Indian children’s oral health.
Rejection, Repurposing and Renewal of the Self: Bodies as Texts in the Erotic Poetries of Carlos Drummond de Andrade and Ronaldo Wilson

This article presents a unique uncommon intertextual staging of two erotic poets whose writings intersect and divide at times, thematically and cross-temporally, to challenge our understanding of the erotic’s liminality. I examine the erotic poetry of Carlos Drummond de Andrade in O amor natural and Ronaldo Wilson’s Poems of the Black Object and Narrative of the Life of the Brown Boy and the White Man, to understand how the body is used to explore identity (re)construction. I show how the incorporation of the body as a source of expression in poetry can be read as transgressive, especially in these pieces.
Splicing factor SRSF1 is indispensable for regulatory T cell homeostasis and function.

The ability of regulatory T (Treg) cells to control the immune response and limit the development of autoimmune diseases is determined by distinct molecular processes, which are not fully understood. We show here that serine/arginine-rich splicing factor 1 (SRSF1), which is decreased in T cells from patients with systemic lupus erythematosus, is necessary for the homeostasis and proper function of Treg cells, because its conditional absence in these cells leads to profound autoimmunity and organ inflammation by elevating the glycolytic metabolism and mTORC1 activity and the production of proinflammatory cytokines. Our data reveal a molecular mechanism that controls Treg cell plasticity and offer insights into the pathogenesis of autoimmune disease.