cssi/SciSciGPT-SciSciNet huggingface dataset:
Pressure Assisted Crystallization of MnAl Thin Films

The effect of hot isostatic pressure processing (HIP) on MnAl films has been compared to vacuum annealing for the purpose of obtaining substantial amounts of tau phase MnAl in films under 200 nm. Films were deposited by dc sputtering from both MnAlNiC an MnAl targets. As-deposited films were nearly amorphous. Post deposition annealing in vacuum produced only small amounts of the ferromagnetic tau-phase in films thinner than 200 nm. In all instances, regardless of substrate and sputtering target, the use of HIP in place of vacuum annealing increased the degree of crystallinity of the samples when compared to those annealed in vacuum. For the 100 nm samples deposited from the MnAlNiC target, these changes in crystallinity were accompanied by changes in the M-H loops of the samples. MnAlNiC HIP samples had improved magnetic properties compared to those of equal thickness annealed in vacuum. The 100 nm HIP sample sputtered from the MnAl target also showed an increase in moment, though the changes were not as dramatic as those seen in the samples sputtered from the MnAlNiC target. The 50 nm films from both targets also showed a change in crystallinity when compared to vacuum annealed samples. These films, unlike the 100 nm films, had ferromagnetic properties that were no better than those of the vacuum annealed samples. This suggests that while the 2 kbar of pressure used in this study assists in the formation of tau-phase in 100 nm films, the appropriate pressure for forming tau-phase in 50 nm films is yet to be determined.
Random Perturbations of Aeroelastic and Mechanical Systems

Abstract Nonlinearity and noise play a significant role in an enormous range of subjects across the entire spectrum of science and engineering. This paper integrates the ideas from random dynamical systems, homogenization methods and Monte Carlo methods to develop a general collection of new mathematical techniques that describe the behavior of the complex dynamical systems.
Building Hope for Positive Youth Development: Research, Practice, and Policy

Within the field of positive youth development (PYD), a key goal is to identify strengths of youth that will help explain why some adolescents are able to develop into successful young adults by working toward productive goals and selecting positive behaviors, whereas others follow developmental paths marked by problematic behaviors. In this chapter, we describe the importance of hope in positive development. We define hope as having three key ingredients: intentional self-regulation, positive future expectations, and connectedness. We provide evidence from the 4-H Study of PYD to show how these three ingredients work together to promote the Five Cs of PYD and youth contribution. We make recommendations for practitioners to incorporate or enhance each of these hope ingredients in their youth development programs as well as how to recognize hopelessness among youth and how to intervene. We conclude the chapter with priorities for youth policy, such as allocating funding for programs and program evaluations that take a comprehensive and integrative approach to youth development programming. We believe that hope should be a cornerstone of youth programming and that practitioners, researchers, and policy-makers can be intentional in promoting hope to ensure all young people have opportunities to thrive.
Federal Legislation and the Future of Surgical Practice

The author reviews past effects of federal legislation on surgical practice and the present status of federal legislative influence. Hope for the future of maintained excellence in surgical practice must lie with the education of the public, who are responsible for electing legislators.
Mating Behavior of the Endemic Hawaiian Cricket Leptogryllus elongatus (Orthoptera: Gryllidae: Oecanthinae)

Hawaiian tree crickets are remarkably speciose and phenotypically diverse and yet we know very little about their behavior. I present the first description of courtship and mating in a member of this group. Leptogryllus elongatus Perkins inhabit the hollow fronds of giant tree ferns on the windward slope of Mauna Kea, on the Big Island of Hawaii. Unlike all other tree crickets, except for the closely related genus Thaumatogryllus, Leptogryllus lack a stridulum to produce song and have no auditory tympanum. In the absence of song, courtship in L. elongatus appears to be vibratory and tactile, in the form of tremulation and tapping of the male cerci against the body of the female. Tremulation by male L. elongatus takes the form of a rhythmic “push-up” beginning at first contact and continuing until the postcopulatory dismount. During courtship, the male maneuvers his abdomen beneath the female and the female dorsally mounts the male. As in other tree crickets, copulation results in transfer of a small spermatophore composed on a external sperm sack and a tube running inside the genitalia of the dorsally mounted female. The rate of tremulation is relatively constant from first contact until copulation. Tremulation rate decreases after spermatophore transfer but increases dramatically when the female begins to move off the male. Another key difference is the lack of metanotal gland feeding in L. elongatus. Nevertheless, L. elongatus display prolonged postcopulatory mounted courtship which delays removal of the spermatophore by the female.
RIP for Dielectrics

The continued success of Si integrated circuit (IC) technology has virtually benefited every industry. The major impacts have been in the areas of computation, information, automobiles, entertainment, medical, and defense industries.
Examine the Potential of Robots to Teach Autistic Children Emotional Concepts: A Preliminary Study

In this preliminary study, we developed a set of humanoid robot body movements which are used to express four basic emotional concepts and a set of learning activities. The goal of this study is to collect feedback from subject matter experts and validate our design. We will integrate them to improve the designs and guide autistic children to learn emotional concepts. To validate our designs, we conducted an online survey among general public people and four in-person interviews among subject matter experts. Results show that the body movement Happiness and Sadness could express emotions accurately, while the Anger and Fear movements need more improvements. According to the subject matter experts, this robot mediate instruction is engaging and appropriate. To better match autistic children, the instructional content should be tailored for individual learners.
A new approach to protein structure mining and alignment

One of the largest areas of focus in bioinformatic and data mining research has been on the protein domain. These research efforts have included protein structure prediction, folding pathway prediction, sequence alignment, ab initio simulation, structure alignment, substructure detection and many others. In this work, we deal with substructure detection and sequence alignment. Substructure detection is generally defined as the mining of a molecule's 3D structure in order to find interesting/frequent domains. Sequence alignment involves determining the similarity of two (or more) protein molecules based on the how well their amino acid sequences "match." There are potential pitfalls when trying solve both of these problems, however. In the case of substructure mining, focusing solely on structural information can lead to the discovery of biologically irrelevant substructures. With sequence alignment, the alignment results can vary greatly, depending on the substitution matrix used. In this paper we describe a method that combines the benefits of both substructure mining and sequence alignment in an attempt to determine the similarity between protein molecules. In the absence of biological information, our work will quickly and efficiently mine a protein molecule in order to determine frequent local structures. With the addition of biological sequence information, however, our algorithm provides a way to align proteins with similar local structures and sequence, yielding a global alignment between molecules. We present a novel structure mining/alignment algorithm as well as some additional work into a new clustering metric for amino acids based on several different physiochemical properties. This metric is used with our alignment algorithm in order to provide a mechanism for globally aligning protein molecules.
See measurements on bulk samples of lucite and lexan

The measurement of secondary electron emission (SEE) coefficients of many materials is covered in detail in the book by Bruining [1]. Some of the current interest in the SEE is generated by the importance of the electron multiplication process in the surface flashover of insulators in high voltage equipment [2]. Measurement of the SEE on the surface of dielectrics is difficult and only a few reports exist in the literature [3]. The major experimental problem is the charging which occurs on the dielectric surface when the SEE coefficient is not equal to one. This problem has been overcome by some experimenters by using such thin films of the dielectric that charge deposited on the surface would leak off rapidly through the material in spite of the high resistivity [4]. This approach is suitable for investigating the fundamental properties of materials but may not be relevant to the properties of, a commercially produced material from which an insulator is produced. Accordingly, we have devised a method by which bulk samples can be tested.
Visualization of big high dimensional data in a three dimensional space

This paper studies feasibility and scalable computing processes for visualizing big high dimensional data in a 3 dimensional space by using dimension reduction techniques. More specifically, we propose an unsupervised approach to compute a measure that is called visualizability in a 3 dimensional space for a high dimensional data. This measure of visualizability is computed based on the comparison of the clustering structures of the data before and after dimension reduction. The computation of visualizability requires finding an optimal clustering structure for the given data sets. Therefore, we further implement a scalable approach based on K-Means algorithm for finding an optimal clustering structure for the given big data. Then we can reduce the volume of a given big data for dimension reduction and visualization by sampling the big data based on the discovered clustering structure of the data.
A multidomain enzyme, with glycerol-3-phosphate dehydrogenase and phosphatase activities, is involved in a chloroplastic pathway for glycerol synthesis in Chlamydomonas reinhardtii

Summary Understanding the unique features of algal metabolism may be necessary to realize the full potential of algae as feedstock for the production of biofuels and biomaterials. Under nitrogen deprivation, the green alga C. reinhardtii showed substantial triacylglycerol (TAG) accumulation and up-regulation of a gene, GPD2, encoding a multidomain enzyme with a putative phosphoserine phosphatase (PSP) motif fused to glycerol-3-phosphate dehydrogenase (GPD) domains. Canonical GPD enzymes catalyze the synthesis of glycerol-3-phosphate (G3P) by reduction of dihydroxyacetone phosphate (DHAP). G3P forms the backbone of TAGs and membrane glycerolipids and it can be dephosphorylated to yield glycerol, an osmotic stabilizer and compatible solute under hypertonic stress. Recombinant Chlamydomonas GPD2 showed both reductase and phosphatase activities in vitro and it can work as a bifunctional enzyme capable of synthesizing glycerol directly from DHAP. In addition, GPD2 and a gene encoding glycerol kinase were up-regulated in Chlamydomonas cells exposed to high salinity. RNA-mediated silencing of GPD2 revealed that the multidomain enzyme was required for TAG accumulation under nitrogen deprivation and for glycerol synthesis under high salinity. Moreover, a GPD2-mCherry fusion protein was found to localize to the chloroplast, supporting the existence of a GPD2-dependent plastid pathway for the rapid synthesis of glycerol in response to hyperosmotic stress. We hypothesize that the reductase and phosphatase activities of PSP-GPD multidomain enzymes may be modulated by post-translational modifications/mechanisms, allowing them to synthesize primarily G3P or glycerol depending on environmental conditions and/or metabolic demands in algal species of the core Chlorophytes. This article is protected by copyright. All rights reserved.
Estimations of membrane potentials in Streptococcus faecalis by means of a fluorescent probe

Membrane potentials in Streptococcus faecalis (faecium) were estimated by means of the fluorescent probe, 1,1′-dihexyl-2,2′-oxycarbocyanine. In the absence of D-glucose the potential was −60 to −70 mV for normal cells suspended in 0.09 M NaCl + 0.01 M Tris-HCl at pH 7.5. When metabolism was initiated by the addition of D-glucose the cells became hyperpolarized (internal becomes more negative). The new potential, −130 to −140 mV, was fully manifested 35 seconds after the glucose was added. N,N′-dicyclohexylcarbodiimide, a membrane ATPase inhibitor prevented the hyperpolarization seen upon the addition glucose. The results are consistent with the view that glycolyzing cells generate a considerasble electrical potential across the cell membrane.
Historical Geoinformation on the Web: Lessons Learned from the Chapter 91 Pilot Project

Publisher Summary This chapter describes the “New Bedford, Massachusetts Chapter 91” website. It is a licensing program that has been continuously enforced in Massachusetts since 1866. Individuals, corporations, and public agencies must obtain permits to place new structures or fills, change the use of existing structures or fills, or dredge in Massachusett's tidelands. In the years 2000-2001, a pilot project was conducted to test the feasibility of transferring the Chapter 91 database, which consists of about 20,000 licenses to a digital format. The project involved the creation of a geographical database, and the design of a website through which the public can access Chapter 91 information. The website is limited to New Bedford, which is one of the two areas chosen for the pilot project and is composed of four main parts: an explanatory section on Chapter 91, a feedback link, a section describing the pilot project, and a section containing the database. The website exemplifies the difficulties of using geographic information technologies with historical data and shows the benefits of adding multimedia capabilities to geographic information system (GIS) and cartography.
Central Nervous System Imaging

Brain tumor imaging has four main goals, namely, evaluating lesion extent, estimating tumor grade, identifying associated complications, and defining a comprehensive differential diagnosis. It assesses the relationship of the lesion to various brain structures and identifies associated findings, such as increased intracranial pressure, impending herniation, hydrocephalus, hemorrhagic transformation, and mass effect. A comprehensive differential diagnosis is usually established based on the patient’s age, tumor location, and specific imaging findings.
Cluster analysis describes constellations of cardiac anomalies presenting in spinal anomaly patients.

Cardiac anomalies are prevalent in patients with bony spinal anomalies. Prior studies evaluating incidences of bony congenital anomalies of the spine are limited. The Kids’ Inpatient Database (KID) yields national discharge estimates of rare pediatric conditions like congenital disorders. This study utilized cluster analysis to study patterns of concurrent vertebral anomalies, anal atresia, cardiac malformations, trachea-esophageal fistula, renal dysplasia, and limb anomalies (VACTERL anomalies) co-occurring in patients with spinal congenital anomalies. Retrospective review of KID 2003–2012. KID-supplied hospital- and year-adjusted weights allowed for incidence assessment of bony spinal anomalies and cardiac, gastrointestinal, urinary anomalies of VACTERL. K-means clustering assessed relationships between most frequent anomalies within bony spinal anomaly discharges; k set to n − 1(n = first incidence of significant drop/little gain in sum of square errors within clusters). There were 12,039,432 KID patients 0–20 years. Incidence per 100,000 discharges: 2.5 congenital fusion of spine, 10.4 hemivertebra, 7.0 missing vertebra. The most common anomalies co-occurring with bony vertebral malformations were atrial septal defect (ASD 12.3%), large intestinal atresia (LIA 11.8%), and patent ductus arteriosus (PDA 10.4%). Top congenital cardiac anomalies in vertebral anomaly patients were ASD, PDA, and ventricular septal defect (VSD); all three anomalies co-occur at 6.6% rate in this vertebral anomaly population. Cluster analysis revealed that of bony anomaly discharges, 55.9% of those with PDA had ASD, 34.2% with VSD had PDA, 22.9% with LIA had ASD, 37.2% with ureter obstruction had LIA, and 35.5% with renal dysplasia had LIA. In vertebral anomaly patients, the most common co-occurring congenital anomalies were cardiac, renal, and gastrointestinal. Top congenital cardiac anomalies in vertebral anomaly patients were ASD, PDA, and VSD. VACTERL patients with vertebral anomalies commonly presented alongside cardiac and renal anomalies.
Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices

The popularity of non-invasive cosmetic improvement of the skin has continued to grow amongst patients and practitioners alike.
Neuroendocrine basis of seasonal reproduction.

Publisher Summary This chapter discusses the strategy of seasonal breeding, the role of photoperiod in timing the annual reproductive cycle, the hypothalamo-pituitary mechanisms that mediate photoperiodic regulation of estrous cyclicity, and the photoperiodic pathway to luteinizing hormone (LH) pulse generator. To understand how photic input to the LH pulse generator leads to seasonal changes in gonadal activity, the sequence of endocrine events that normally leads to ovulation during the estrous cycle of the ewe must be considered. These preovulatory events occur during a 2–3 day follicular phase and include a precipitous drop in progesterone, a progressive rise in tonic LH secretion, a sustained increase in estradiol secretion, and the LH surge. The pivotal step in this sequence is the sustained increase in tonic LH secretion. A great deal of insight has been gained into the complex interplay between the neural and endocrine response systems that underlie the seasonal reproductive process in the short-day breeding ewe. Specifically, light cues activate retinal photoreceptors and are transmitted via a monosynaptic tract to the suprachiasmatic nuclei of the hypothalamus. After interacting with the circadian system, the photic information is relayed to the pineal gland that transduces the neural message into a hormonal signal in the form of a circadian rhythm of melatonin secretion. The pattern of this melatonin signal, which is interpreted as inductive or suppressive, sets the frequency of the LH pulse generator and determines the capacity of this neural oscillator to respond to the negative feedback action of estradiol. The resulting changes in the episodic pattern of gonadotropin secretion, in turn, dictate whether or not estrous cycles can occur.
Evaluation and differential diagnosis of keratoconjunctivitis sicca.

Patients with S ogren's syndrome (SS) have a high incidence of immune mediated ocular inflammation, making them more susceptible to infectious agents. However, the more common manifestation seen in patients with SS is immune mediated noninfectious inflammation of the lacrimal glands and ocular surface, resulting in decreased tear production and inflammatory changes on the ocular surface known as SS associated keratoconjunctivitis sicca (SS-KCS). Two categories of SS-KCS are recognized: aqueous deficient dry eye (decreased tear production by lacrimal glands) and evaporative dry eye (increased evaporative loss of tears from the ocular surface). There are a variety of tests for the differential diagnosis of SS-KCS, including the Schirmer test, with or without anesthetic; vital dye staining of the ocular surface for surface abnormalities; tear osmolarity; and lid margins evaluation. Current treatment of KCS involves artificial tears and punctal occlusion. New and emerging treatment options using androgens to suppress glandular inflammation and muscarinic M3 agonists, i.e., cevimeline and pilocarpine, show promise as treatment options for SS-KCS.
Carbonic Anhydrase Inhibition and Cerebral Cortical Oxygenation in the Rat

The carbonic anhydrase inhibitor, acetazolamide (Maren, 1967), has been used clinically for many years as a treatment for the prevention of the symptoms, primarily headaches, of acute exposure to altitude hypoxia, as originally demonstrated by Cain and Dunn (1966). This effect was thought to be due to a drug-induced metabolic acidosis that compensated for an altitude-induced respiratory alkalosis. Furthermore, it had already been noticed that acetazolamide administration was followed by increased cerebral blood flow (Cotev et al., 1968; Ehrenreich et al., 1961; Posner and Plum, 1960), an observation that has often been confirmed since. Nevertheless, the effects of acetazolamide on metabolism and blood flow in the brain and their relationships to the physiological mechanisms of action of acetazolamide have not been well studied.
Modification of Food Proteins by Non-Enzymatic Methods

The effective utilization of proteins in food systems is dependent on tailoring the protein’s functional characteristics to meet the complex needs of the manufactured food products. Many food proteins, particularly those from plant sources, require modification to improve such functional properties as solubility, whippability and emulsification activity. Chemical treatments used for modification can be classified into two main groups: enzymatic and non-enzymatic methods. This chapter concerns chemical methods that modify food proteins non-enzymatically. For enzymatic modification, the reader should refer to Chapter 8 of this book. Even though enzymatic modifications are considered safer for food uses and therefore more desirable, many non-enzymatic methods have been proven safe. Indeed, because of their simple approach, ready availability and great effectiveness, non-enzymatic methods are always desirable and often irreplaceable. Reviews on food protein modifications for improved functionality are available in the literature.1–3 This review covers only non-enzymatic modifications with an emphasis on current developments.
Gut Disease in Systemic Sclerosis—New Approaches to Common Problems

The goal of this manuscript is to discuss the new diagnostic and potential treatment options for gut disease in systemic sclerosis (SSc). The concepts of quantification of gut perfusion and motility are reviewed. The risks of empiric therapeutics and challenges of studying the microbiome in SSc are discussed. There are diagnostics that can provide information on gut perfusion and function that are of value in SSc. Easily implemented diagnostic tests are critical to avoid complications of empiric therapy. The role of the microbiome and drugs that target dysmotility are areas of active research. SSc-related gastrointestinal tract involvement can be heterogeneous in clinical presentation and disease course. Noninvasive gastrointestinal measurement techniques that quantify neural communications with microvasculature in SSc can potentially guide the proper addition and discontinuation of therapeutics. The role of the microbiome and the role of nitric oxide on gut function are important areas of research for understanding gut dysfunction in SSc.
The effect of supplementation of vitamin D in neurocritical care patients: RandomizEd Clinical TrIal oF hYpovitaminosis D (RECTIFY)

OBJECTIVE Hypovitaminosis D is prevalent in neurocritical care patients, but the potential to improve patient outcome by replenishing vitamin D has not been investigated. This single-center, double-blinded, placebo-controlled, randomized (1:1) clinical trial was designed to assess the effect on patient outcome of vitamin D supplementation in neurocritical care patients with hypovitaminosis D. METHODS From October 2016 until April 2018, emergently admitted neurocritical care patients with vitamin D deficiency (≤ 20 ng/ml) were randomized to receive vitamin D3 (cholecalciferol, 540,000 IU) (n = 134) or placebo (n = 133). Hospital length of stay (LOS) was the primary outcome; secondary outcomes included intensive care unit (ICU) LOS, repeat vitamin D levels, patient complications, and patient disposition. Exploratory analysis evaluated specific subgroups of patients by LOS, Glasgow Coma Scale (GCS) score, and Simplified Acute Physiology Score (SAPS II). RESULTS Two-hundred seventy-four patients were randomized (intent-to-treat) and 267 were administered treatment within 48 hours of admission (as-treated; 61.2% of planned recruitment) and monitored. The mean age of as-treated patients was 54.0 ± 17.2 years (56.9% male, 77.2% white). After interim analysis suggested a low conditional power for outcome difference (predictive power 0.12), the trial was halted. For as-treated patients, no significant difference in hospital LOS (10.4 ± 14.5 days vs 9.1 ± 7.9 days, p = 0.4; mean difference 1.3, 95% CI -1.5 to 4.1) or ICU LOS (5.8 ± 7.5 days vs 5.4 ± 6.4 days, p = 0.4; mean difference 0.4, 95% CI -1.3 to 2.1) was seen between vitamin D3 and placebo groups, respectively. Vitamin D3 supplementation significantly improved repeat serum levels compared with placebo (20.8 ± 9.3 ng/ml vs 12.8 ± 4.8 ng/ml, p < 0.001) without adverse side effects. No subgroups were identified by exclusion of LOS outliers or segregation by GCS score, SAPS II, or severe vitamin D deficiency (≤ 10 ng/ml). CONCLUSIONS Despite studies showing that vitamin D can predict prognosis, supplementation in vitamin D-deficient neurocritical care patients did not result in appreciable improvement in outcomes and likely does not play a role in acute clinical recovery.Clinical trial registration no.: NCT02881957 (clinicaltrials.gov).
Scientism recognizes evidence only of the quantitative/general variety

Rationale, aims and objectives McHugh and Walker introduced a model of knowledge to demonstrate that EBM is a form of scientism that ignores important sources of knowledge thereby impairing the practice of medicine. We study the development of this model and explore additional applications. Methods Review of the relevant literature and identification of possible areas for fruitful application. Results We show that the McHugh and Walker model is closely related to the model of evidence considered earlier by Upshur et al. We also indicate that the utility of this model is not limited to showing scientism distorts clinical practice. Several representative applications are identified, including psychotherapy, the Salk polio vaccine trial, and the placebo effect. Conclusions Priority should be given to Upshur et al for the development of a model that has far-reaching application to medical epistemology. It is shown that all four of the types of evidence considered-qualitative/personal, qualitative/general, quantitative/general, and quantitative/personal-are required to adequately characterize epistemology in medical research and practice.
Compact ultrafast fiber lasers for multiphoton microscopy and precision measurements

We present on the development of ultrafast fiber lasers and their applications in nonlinear optical imaging and precision measurements. These compact femtosecond lasers have enabled multiphoton imaging of biological samples [1], precision rotation measurement [2], and gas sensing applications [3, 4]. Our multiphoton microscopes have enabled label free determination of the stages of dysplasia in Barrett’s esophagus [5], pancreatic cancer margin detection [6], and examined the nonlinear optical properties of materials [7]. We have also achieved real-time dual-comb spectroscopy measurements of gases without the need for complex servo locking systems with a high signal to noise ratio [8]. With these systems, we can gather sample information not available with traditional microscopy, create precision rotation sensing systems unlike any existing market solution, and resolve narrow absorption lines without the need for complex equipment.
A 7-nm FinFET CMOS PLL With 388-fs Jitter and −80-dBc Reference Spur Featuring a Track-and-Hold Charge Pump and Automatic Loop Gain Control

This article presents a phase-locked loop (PLL) design that overcomes design challenges imposed by FinFET CMOS nodes, notably high gate resistance and middle-end-of-line parasitics. We propose a track-and-hold charge pump (THCP) and an automatic loop gain control, which not only overcome these challenges but also improve the PLL jitter and reference spur performance. The proposed THCP achieves −115-dBc/Hz in-band phase noise while consuming only $53~\mu \text{W}$ , which is less than 1% of total PLL power consumption. The ring-based PLL achieves both 388-fsrms integrated jitter and reference spurs at −80 dBc. At 4.0 GHz, this PLL consumes 5.9 mW from a 0.9-V supply, translating to a figure of merit of −240.5 dB. The PLL is fabricated in the TSMC 7-nm FinFET CMOS technology.
Exploring Intercultural Communication. Language in Action: Zhu Hua. 2nd edition. London and New York: Routledge, 2018, 304 pp., ISBN 978-1315159010

?Cual es la relacion entre lenguaje, cultura y pensamiento?, ?que es lo que hace que la cultura sea relevante para alguien, en que contexto y con que propositos?, ?son todas las turbulencias que ap...
A high-affinity, partial antagonist effect of 3,4-diaminopyridine mediates action potential broadening and enhancement of transmitter release at NMJs.

3,4-Diaminopyridine (3,4-DAP) increases transmitter release from neuromuscular junctions (NMJs), and low doses of 3,4-DAP (estimated to reach ∼1 μM in serum) are the Food and Drug Administration (FDA)-approved treatment for neuromuscular weakness caused by Lambert-Eaton myasthenic syndrome. Canonically, 3,4-DAP is thought to block voltage-gated potassium (Kv) channels, resulting in prolongation of the presynaptic action potential (AP). However, recent reports have shown that low millimolar concentrations of 3,4-DAP have an off-target agonist effect on the Cav1 subtype ("L-type") of voltage-gated calcium (Cav) channels and have speculated that this agonist effect might contribute to 3,4-DAP effects on transmitter release at the NMJ. To address 3,4-DAP's mechanism(s) of action, we first used the patch-clamp electrophysiology to characterize the concentration-dependent block of 3,4-DAP on the predominant presynaptic Kv channel subtypes found at the mammalian NMJ (Kv3.3 and Kv3.4). We identified a previously unreported high-affinity (1-10 μM) partial antagonist effect of 3,4-DAP in addition to the well-known low-affinity (0.1-1 mM) antagonist activity. We also showed that 1.5-μM DAP had no effects on Cav1.2 or Cav2.1 current. Next, we used voltage imaging to show that 1.5- or 100-μM 3,4-DAP broadened the AP waveform in a dose-dependent manner, independent of Cav1 calcium channels. Finally, we demonstrated that 1.5- or 100-μM 3,4-DAP augmented transmitter release in a dose-dependent manner and this effect was also independent of Cav1 channels. From these results, we conclude that low micromolar concentrations of 3,4-DAP act solely on Kv channels to mediate AP broadening and enhance transmitter release at the NMJ.
Implementation of a Chatbot Mobile Health Intervention with Home Spirometry to Monitor Lung Transplant Recipients Remotely

Purpose The COVID-19 pandemic accelerated the need to develop remote monitoring of graft function in lung transplant (LT) recipients. While home spirometry has been used previously in LT, long-term engagement has been poor. We aimed to improve engagement and allow efficient data and symptom collection using Bluetooth enabled home spirometers coupled with a digital chatbot. Methods We implemented an automated, chat-based mobile health intervention via text message or email paired with Bluetooth-enabled hand-held spirometers. The chatbot engaged LT recipients weekly in a personalized, automated chat with symptom assessment, education modules, and spirometer data collection. Clinical team members received automatic notification of concerning symptoms or FEV1 declines of >10%. The correlation between home spirometry FEV1 values and lab-based values were assessed with Pearson's coefficient. Results We mailed home spirometers to 424 patients. Between 5/4/2020 and 10/21/2020, 311 patients enrolled in the automated chat and, of these, 273 patients submitted ≥1 FEV1 measure, (median 13; IQR 6-23) over 24 weeks. The largest drop in FEV1 engagement came after the first week in each patient's chat experience; 65% of those that submitted an FEV1 at baseline entered a value at week one and 72% at week two. However, after this initial decline, engagement remained stable through 24 weeks (57-72%, Figure 1.A). Home spirometry FEV1 correlated closely with in-lab spirometry (rho = 0.94) (Figure 1.B) Conclusion LT recipients engaged at high rates with a chatbot mobile health intervention and home spirometers to report their FEV1, allowing reliable home-based monitoring of LT recipients. Further investigation will be needed to improve engagement further. Given the projected need for social distancing, and increasing role of telemedicine for long-term management, a chatbot-linked home spirometer may be a powerful tool to detect early graft dysfunction.
The Development, Implementation, and Evaluation of an Acute Otitis Media Education Website.

Abstract Objective To develop, implement, and evaluate an acute otitis media (AOM) education website for clinician-educators. Methods We developed an education website following Kern's curriculum model. Results The website contained peer-reviewed content, educational objectives, library search pages to identify evidence-based resources, and a faculty toolbox with instructional and evaluation instruments. Pediatric clinician-educators were purposefully sampled from different clinic sites to evaluate the website. Semistructured interviews explored key website components for content and usability in clinical teaching. In grounded theory tradition, investigators used the constant comparative method with qualitative analysis software to identify themes and representative quotations. Eleven faculty members (9 females and 2 males with teaching experience from 6 to 26 years) participated in the study. Identified themes were: 1) value of visual impact for learning specific topics, 2) promotion of efficiency in teaching clinical topics, 3) varying approaches for using website, and 4) faculty's self-report of knowledge and self-efficacy needs. Conclusions An education website may enhance the teaching of AOM, accommodate different teaching preferences, promote efficiency in teaching, and advance clinician-educator knowledge and skills. Next steps include evaluation of learners’ perspectives, generalizability in varied teaching settings, and assessment of higher learning outcomes including impact on knowledge, skills, and patient outcomes.
Use of UHPC Jackets in Coastal Bridge Piles

Concrete deteriorates for a variety of reasons, but corrosion of steel reinforcement has been one of the most prevalent mechanisms of deterioration since concrete structures were introduced in the early 1900s. It affects many types of concrete elements, especially the substructures of coastal bridges. Steel reinforcement used in coastal bridge piles has exhibited corrosion damage within twenty years of construction. Therefore, it degrades the durability and reduces the service life of the bridges severely. As a result, it costs billions of dollars in rehabilitating or repairing the deficient components. The recent development of UHPC can mitigate these deficiencies because of its exceptional properties. However, the cost of UHPC is significantly higher than that of the conventional concrete. Therefore, it appears to be attractive to use UHPC jackets in coastal bridge piles, which allows to taking advantage of the superior properties of UHPC without using excessive amount of UHPC in the full section. This paper presents a study of the structural design of piles using UHPC jackets, including the working stress design and strength design. A numerical example of a square pile using a UHPC jacket is included to show how the flexural strength design can be handled.
Single-cell multiomics dissection of basal and antigen-specific activation states of CD19-targeted CAR T cells.

Background Autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 molecule have transformed the therapeutic landscape in patients with highly refractory leukemia and lymphoma, and the use of donor-generated allogeneic CAR T is paving the way for further breakthroughs in the treatment of cancer. However, it remains unknown how the intrinsic heterogeneities of these engineered cells mediate therapeutic efficacy and whether allogeneic products match the effectiveness of autologous therapies. Methods Using single-cell mRNA sequencing in conjunction with CITE-seq, we performed multiomics characterization of CAR T cells generated from healthy donor and patients with acute lymphoblastic leukemia. CAR T cells used in this study were manufactured at the University of Pennsylvania through lentiviral transduction with a CD19-4-1BB-CD3ζ construct. Besides the baseline condition, we engineered NIH-3T3 cells with human CD19 or mesothelin expression to conduct ex vivo antigen-specific or non-antigen stimulation of CAR T cells through 6-hour coculture at a 1:1 ratio. Results We delineated the global cellular and molecular CAR T landscape and identified that transcriptional CAR tonic signaling was regulated by a mixture of early activation, exhaustion signatures, and cytotoxic activities. On CD19 stimulation, we illuminated the disparities of CAR T cells derived from different origins and found that donor CAR T had more pronounced activation level in correlation with the upregulation of major histocompatibility complex class II genes compared with patient CAR T cells. This finding was independently validated in additional datasets from literature. Furthermore, GM-CSF(CSF2) expression was found to be associated with functional gene productions, but it induced little impact on the CAR T activation. Conclusions Through integrated multiomics profiling and unbiased canonical pathway analyses, our results unveil heterogeneities in the transcriptional, phenotypic, functional, and metabolic profiles of donor and patient CAR T cells, providing mechanistic basis for ameliorating clinical outcomes and developing next-generation ‘off- the-shelf’ allogeneic products.
Evaluating the risk of SARS-CoV-2 transmission to bats using a decision analytical framework

Preventing wildlife disease outbreaks is a priority issue for natural resource agencies, and management decisions can be urgent, especially in epidemic circumstances. With the emergence of SARS-CoV-2, wildlife agencies were concerned whether the activities they authorize might increase the risk of viral transmission from humans to North American bats but had a limited amount of time in which to make decisions. We provide a description of how decision analysis provides a powerful framework to analyze and re-analyze complex natural resource management problems as knowledge evolves. Coupled with expert judgment and avenues for the rapid release of information, risk assessment can provide timely scientific information for evolving decisions. In April 2020, the first rapid risk assessment was conducted to evaluate the risk of transmission of SARS-CoV-2 from humans to North American bats. Based on the best available information, and relying heavily on formal expert judgment, the risk assessment found a small possibility of transmission during summer work activities. Following that assessment, additional knowledge and data emerged, such as bat viral challenge studies, that further elucidated the risks of human-to-bat transmission and culminated in a second risk assessment in the fall of 2020. We update the first SARS-CoV-2 risk assessment with new estimates of little brown bat (Myotis lucifugus) susceptibility and new management alternatives, using findings from the prior two risk assessments and other empirical studies. We highlight the strengths of decision analysis and expert judgment not only to frame decisions and produce useful science in a timely manner, but also to serve as a framework to reassess risk as understanding improves. For SARS-CoV-2 risk, new knowledge led to an 88% decrease in the median number of bats estimated to be infected per 1000 encountered when compared to earlier results. The use of facemasks during, or a negative COVID-19 test prior to, bat encounters further reduced those risks. Using a combination of decision analysis, expert judgment, rapid risk assessment, and efficient modes of information distribution, we provide timely science support to decision makers for summer bat work in North America.
Establishing a Pecking Order for Finance Academics: Ranking of US Finance Doctoral Programs

The ranking of colleges, programs, departments and faculties has reached a feverish pitch in recent years. Missing from the vast list of rankings is research covering doctoral programs in finance. This study ranks 91 US finance doctoral programs based on productivity of current finance department faculty, graduates of those programs, and a survey of doctoral program directors/chairs. The resulting rankings should be of value to those seeking to earn a finance doctorate in the future as well as satisfy the natural curiosity of finance faculty regarding bragging rights on their respective doctoral programs.
The Risk Seems Too High": Thoughts and Feelings about COVID-19 Vaccination."

The purpose of this study was to describe the thoughts and feelings of individuals expressing concerns about the COVID-19 vaccine. A qualitative descriptive study was conducted in order to examine the thoughts and feelings of participants who are hesitant about the COVID-19 vaccine. Data were collected from 754 participants using an online instrument. Emergent themes included a lack of knowledge about the safety of the COVID-19 vaccine; concerns over the speed of development, testing, and approval of these vaccines; reluctance to be among the first vaccinated; concerns about the motivations of government actors, pharmaceutical companies, and others involved in producing the COVID-19 vaccine; and hesitancy about vaccines generally.
The ovarian hormones and experimental menstruation

Abstract In castrate monkeys menstruation-like bleeding is caused by sudden discontinuance of a course either of estrogenic hormone or of progesterone. When the estrogen and progesterone are given simultaneously in suitable amounts, bleeding occurs if the progesterone is discontinued even though sufficient estrogen to prevent bleeding is still being administered. This observation offers a possible explanation of natural menstruation on the basis of recurrent action and inaction of the corpus luteum. Anovulatory menstruation offers a more obscure problem. The mechanism by which deprivation of the hormones sets up a disturbance of the endometrial blood vessels is still unexplained. From these considerations it is probable that pathologic uterine bleeding may be caused by fluctuations in levels of the ovarian hormones, and that no sharp distinction exists between menstruation and functional metrorrhagia. Such a concept opens the possibility of ultimate control of uterine hemorrhagic diseases.
Simple parallel biconnectivity algorithms for multicore platforms

We present two new algorithms for finding the biconnected components of a large undirected sparse graph. The first algorithm is based on identifying articulation points and labeling edges using multiple connectivity queries, and the second approach uses the color propagation technique to decompose the graph. Both methods use a breadth-first spanning tree and some auxiliary information computed during Breadth-First Search (BFS). These methods are simpler than the Tarjan-Vishkin PRAM algorithm for biconnectivity and do not require Euler tour computation or any auxiliary graph construction. We identify steps in these algorithms that can be parallelized in a shared-memory environment and develop tuned OpenMP implementations. Using a collection of large-scale real-world graph instances, we show that these methods outperform the state-of-the-art Cong-Bader biconnected components implementation, which is based on the Tarjan-Vishkin algorithm. We achieve up to 7.1× and 4.2× parallel speedup over the serial Hopcroft-Tarjan and parallel Cong-Bader algorithms, respectively, on a 16-core Intel Sandy Bridge system. For some graph instances, due to the fast BFS-based preprocessing step, the single-threaded implementation of our first algorithm is faster than the serial Hopcroft-Tarjan algorithm.
Adaptive obstacle avoidance using residual HJB corrections

An algorithm for learning transition cost estimates for obstacle avoidance and path planning in two-dimensional analog-valued obstacle fields is presented. The approximate transition costs are modeled with CMAC (cerebellar model articulated controller) neural architectures. Training sets are generated via residual transition cost model corrections obtained from the principle of optimality equations of dynamic programming, a discrete version of the Hamilton-Jacobi-Bellman (HJB) equation of optimal control. Two obstacle field resolutions, one fine and one coarse, are used to derive the cost updates. The set of updates then provides the next generation of training data to the neural architectures. >
Physiological changes due to age. Implications for drug therapy of congestive heart failure.

The segment of the population considered to be ‘elderly’ is consistently growing. At the same time, the number of patients with congestive heart failure continues to grow. Therefore, it is important to consider whether older patients with congestive heart failure have characteristics that identify an aging effect in addition to the obvious abnormalities produced by heart failure. Furthermore, it is important to determine the relevance of these abnormalities to the use of pharmacological therapy. Within a population of 128 consecutive heart failure patients, age-related increases of systemic vascular resistance, changes in baroreceptor responses, and increases of plasma noradrenaline (norepinephrine) levels were identified. In addition, an age-related reduction of renal function was clearly evident in patients >65 years of age. These changes affect the use of digoxin, diuretics and angiotensin converting enzyme (ACE) inhibitors. Most notably, marked reduction of renal function in such patients must be considered in the drug treatment of heart failure.
The significance of recruiting underrepresented minorities in medicine: an examination of the need for effective approaches used in admissions by higher education institutions.

The purpose of this paper is to examine the significance of recruiting underrepresented minorities in medicine (URM). This would include African Americans, Hispanics, and Native Americans. The research findings support the belief that URMs, upon graduating, are more likely to become practitioners in underserved communities, thereby becoming a resource that prompts us to find effective ways to help increase their college enrollments statewide. This paper analyzes the recruitment challenges for institutions, followed by a review of creative and effective approaches used by organizations and universities. The results have shown positive outcomes averaging a 50% increase in minority enrollments and retention. In other areas, such as cognitive development, modest gains were achieved in programs that were shorter in duration. The results nevertheless indicated steps in the right direction inspiring further program developments. Keywords: underrepresented in medicine; minority recruitment; diversity; medical education (Published: 4 September 2014) Citation: Med Educ Online 2014, 19 : 24891 - http://dx.doi.org/10.3402/meo.v19.24891