cssi/SciSciGPT-SciSciNet huggingface dataset:
3D Printing of Microfluidics for Point of Care Diagnosis

Microfluidic lab-on-a-chip (MLOC) technology is a promising approach for point-of-care (POC) diagnosis; low reagent consumption, high sensitivity and quick analysis time are the most prominent benefits. However, microfabrication of MLOCs utilizes specialized techniques and infrastructure, making conventional fabrication time consuming and difficult. While relatively inexpensive production techniques exist for POC diagnoses, such as replication of polymer-based (e.g., PDMS) microfluidic POC devices on lithographic molds, this approach has limitations including: further hydrophilic surface modifications of PDMS, inability to change lithographic mold Z dimensions, and slow prototyping. In contrast, stereo-lithographical (SLA) printing can integrate all of the necessary fabrication resources in one instrument, allowing highly versatile microfluidic devices to be made at low cost. In this paper, we report two microfabrication approaches of microfluidics utilizing (SLA) 3D printing technology: I) Direct SLA printing of channels and structures of a monolithic microfluidic POC device; II) Indirect fabrication, utilizing SLA 3D printed molds for PDMS based microfluidic device replication. Additionally, we discuss previous work providing a proof of concept of applications in POC diagnosis, using direct 3D printing fabrication (approach I). The robustness and simplicity of these protocols allow integrating 3D design and microfabrication with smartphone-based disease diagnosis as a stand-alone system, offering strong adaptability for establishing diagnostic capacity in resource-limited areas and low-income countries.Copyright © 2017 by ASME
Epigenetic regulation of DNA repair mediated by the histone methyltransferase DOT1L

In eukaryotic cells, the homologous recombination (HR) and non-homologous end joining (NHEJ) pathways are required for the repair of DNA double strand breaks (DSB). In mammals, histone modification and histone variant exchange into nucleosomes at sites of DSB generate an open chromatin state necessary for repair to take place. How histone modifications contribute to histone variant exchange at DSB sites, and how this process results in DNA repair remain unresolved. Here we show that Disruptor of telomeric silencing -1 like (DOT1L) is required for H2A.Z histone variant exchange at DSB sites. Cells from Dot1L-/- mice have increased genomic instability and defects in DNA repair. Loss of either DOT1L or its methylation activity results in decreased H2A.Z incorporation at DSB sites, increased amounts of single strand DNA, and significantly reduced repair activity by homologous recombination.
Turbulent Aeroheating Measurements on a 7-deg Half-Angle Sphere-Cone in a High-Enthalpy CO2 Expansion Tunnel

A database of heating and pressure measurements on a 7-deg half-angle cone in a highenthalpy expansion tunnel in CO2 has been generated to support development and validation of computational models to be employed in the design of future Mars missions. Laminar, transitional, and turbulent simulations were performed at the test conditions for comparisons with the data. Close agreement was obtained for both fully-laminar and fully turbulent conditions. For the remaining transitional/turbulent conditions, agreement to within, or slightly more than, the estimated experimental uncertainty was demonstrated. The influence of transition intermittency and transition length models on predicted heating levels was demonstrated, as were differences in turbulent heating predictions generated using various algebraic, one-equation, and two-equation turbulence models. These comparisons provide some measure of confidence in turbulent simulation capabilities; however, because the data were not obtained on a relevant entry vehicle geometry, it is not possible to fully quantify computational uncertainties for the definition of Mars mission aerothermodynamic environments at this time
Early versus late tracheostomy after decompressive craniectomy for stroke

Stroke patients requiring decompressive craniectomy are at high risk of prolonged mechanical ventilation and ventilator-associated pneumonia (VAP). Tracheostomy placement may reduce the duration of mechanical ventilation. Predicting which patients will require tracheostomy and the optimal timing of tracheostomy remains a clinical challenge. In this study, the authors compare key outcomes after early versus late tracheostomy and develop a useful pre-operative decision-making tool to predict post-operative tracheostomy dependence. We performed a retrospective analysis of prospectively collected registry data. We developed a propensity-weighted decision tree analysis to predict tracheostomy requirement using factors present prior to surgical decompression. In addition, outcomes include probability functions for intensive care unit length of stay, hospital length of stay, and mortality, based on data for early (≤ 10 days) versus late (> 10 days) tracheostomy. There were 168 surgical decompressions performed on patients with acute ischemic or spontaneous hemorrhagic stroke between 2010 and 2015. Forty-eight patients (28.5%) required a tracheostomy, 35 (20.8%) developed VAP, and 126 (75%) survived hospitalization. Mean ICU and hospital length of stay were 15.1 and 25.8 days, respectively. Using GCS, SOFA score, and presence of hydrocephalus, our decision tree analysis had 63% sensitivity and 84% specificity for predicting tracheostomy requirement. The early group had fewer ventilator days (7.3 versus 15.2, p < 0.001) and shorter hospital length of stay (28.5 versus 44.4 days, p = 0.014). VAP rates and mortality were similar between the two groups. Withdrawal of treatment interventions shortly post-operatively confounded mortality outcomes. Early tracheostomy shortens duration of mechanical ventilation and length of stay after surgical decompression for stroke, but it did not impact mortality or VAP rates. A decision tree is a practical tool that may be helpful in guiding pre-operative decision-making with patients’ families.
Sub-anesthetic doses of ketamine attenuate nicotine self-administration in rats.

Abstract Smoking cessation strategies are of prime medical importance. Despite availability of various pharmacological agents in combating addiction to nicotine, more effective medications are needed. Based on recent findings, the glutamatergic system in the brain may provide novel targets. Here, we evaluated the effects of acute administration of sub-anesthetic doses of ketamine, an NMDA receptor antagonist, in both male and female Sprague-Dawley rats trained to self-administer nicotine. Animals were injected subcutaneously with 5, 7.5 and 10 mg/kg ketamine or saline and the effects on the number of intravenous nicotine infusions during a 45 min session was measured. Ketamine treatment significantly reduced nicotine self-administration in a dose-dependent manner. Moreover, a differential sensitivity between the sexes was observed as male rats responded to a lower dose of ketamine and with higher magnitude of effect than female rats. It is concluded that glutamatergic receptor manipulations may offer a novel and potentially sex-dependent intervention in nicotine addiction.
Definitive chemoradiation for locally-advanced oral cavity cancer: A 20-year experience.

Abstract Objectives Definitive chemoradiation (CRT) for oral cavity squamous cell carcinoma (OC-SCC) is often criticized for poor efficacy or toxicity. We describe a favorable 20-year experience of primary CRT for locally-advanced OC-SCC. Materials and Methods Patients with locally-advanced, stage III/IV OC-SCC receiving primary concomitant CRT on protocols from 1994 to 2014 were analyzed. Chemotherapy included fluorouracil and hydroxyurea with other third agents. Radiotherapy (RT) was delivered once or twice daily to a maximum dose of 70–75 Gy. Intensity-modulated RT (IMRT) was exclusively used after 2004. Progression-free survival (PFS), overall survival (OS), locoregional control (LRC), and distant control (DC) were calculated by the Kaplan-Meier method and compared across treatment decades using the log-rank test. Rates of osteoradionecrosis (ORN) requiring surgery were compared across treatment decades using the Chi-square test. Results 140 patients with locally-advanced OC-SCC were treated with definitive CRT. Of these, 75.7% had T3/T4 disease, 68.6% had ≥N2 nodal disease, and 91.4% had stage IV disease. Most common primary sites were oral tongue (47.9%) and floor of mouth (24.3%). Median follow-up was 5.7 years. Five-year OS, PFS, LRC, and DC were 63.2%, 58.7%, 78.6%, and 87.2%, respectively. Rates of ORN and long-term feeding tube dependence were 20.7% and 10.0%, respectively. Differences in LRC (P = 0.90), DC (P = 0.24), PFS (P = 0.38), OS (P = 0.10), or ORN (P = 0.38) were not significant across treatment decades. Conclusion Definitive CRT is a viable and feasible strategy for organ preservation for patients with locally-advanced OC-SCC.
Adiposity, body composition and ventricular-arterial stiffness in the elderly: the Atherosclerosis Risk in Communities Study.

AIM Weight gain appears to accelerate age-related ventricular-arterial stiffening, which has been implicated in the development of heart failure (HF), but it is unclear whether body fat accumulation underpins this association. We evaluated the relationship of adiposity, using measures of body composition, with ventricular-arterial stiffness among the elderly in the community. METHODS AND RESULTS Adiposity was accessed through body mass index (BMI), waist circumference, and body fat percentage. We studied the association of these measures with carotid-femoral pulse wave velocity (cfPWV), arterial elastance index (EaI), left ventricular (LV) end-systolic elastance index (EesI) and LV end-diastolic elastance index (EedI) in 5520 community-based, elderly Atherosclerosis Risk in Communities (ARIC) Study participants, who underwent echocardiography between 2011 and 2013. BMI and waist circumference were directly associated with EaI, EedI and EesI even after adjusting for age, sex, race, hypertension, diabetes mellitus, heart rate, prevalent coronary heart disease and HF. After further adjustment for BMI, body fat percentage demonstrated significant independent linear relationships with EaI [standardized beta coefficient (β)=0.17, P<0.001], EesI (β=0.08, P=0.003) and EedI (β=0.20, P<0.001), and significant non-linear relationships with cfPWV (P=0.033). CONCLUSION In this biracial community-based cohort, increased adiposity was associated with increased ventricular-arterial stiffness among the elderly and suggests a potential mechanism by which obesity might contribute to the development of HF.
Revisiting the plasticity of human spatial cognition

In a recent study by Haun et al. (2011), Dutch-speaking children who prefer an egocentric (left/right) reference frame when describing spatial relationships, and Haillom-speaking children who use a geocentric (north/south) frame were found to vary in their capacity to memorize small-scale arrays using their language-incongruent system. In two experiments, we reconcile these results with previous findings by Li et al. (2011) which showed that English (egocentric) and Tseltal Mayan (geocentric) speakers can flexibly use both systems. In Experiment 1, attempting to replicate Haun et al., we found that English- but not Tseltal-speaking children could use their language-incongruent system. In Experiment 2, we demonstrate that Tseltal children can use an egocentric system when instructed nonverbally without left/right language. We argue that Haun et al.'s results are due to the Haillom children's lack of understanding of left/right instructions and that task constraints determine which system is easier to use.
Decision Making for Emergency Medical Services

When a medical emergency is recognized, citizens of communities across the USA call 9-1-1. As taxpayers, citizens assume that their local Emergency Medical Services (EMS) agency is always ready to respond quickly and provide necessary treatments to save lives, alleviate pain and suffering, or otherwise address citizens’ concerns. Designing and operating EMS emergency response systems is a major area of research which directly affects communities. One of the primary goals of this research is to provide EMS administrators with viable ambulance location models for improving response times. The first step toward improving response times is to improve forecasting methods. Accurate forecasting provides EMS administrators with pertinent information about when and where calls for ambulances are likely to originate. Given this information EMS administrators can then attempt to locate their ambulances to maximize coverage over a given geographical area. However, calls for ambulances vary both temporally and spatially, forcing EMS administrators to frequently relocate their ambulances as demand patterns change. Forecasting the changes in these demand patterns, as well as determining the different locations ambulances need to be placed at different times of the day, is an important aspect in the successful day-to-day operations for any EMS administrator. However, frequent relocations cause fatigue and loss of morale among ambulance personnel. Our research enables EMS administrators to address these concerns while delivering highest-quality service with limited resources.
Cicerone: stereotactic neurophysiological recording and deep brain stimulation electrode placement software system

Stereotactic neurosurgery and neurophysiological microelectrode recordings in both humans and monkeys are typically done with conventional 2D atlases and paper records of the stereotactic coordinates. This approach is prone to error because the brain size, shape, and location of subcortical structures can vary between subjects. Furthermore, paper record keeping is inefficient and limits opportunities for data visualization. To address these limitations, we developed a software tool (Cicerone) that enables interactive 3D visualization of co-registered magnetic resonance images (MRI), computed tomography (CT) scans, 3D brain atlases, neurophysiological microelectrode recording (MER) data, and deep brain stimulation (DBS) electrode(s) with the volume of tissue activated (VTA) as a function of the stimulation parameters. The software can be used in pre-operative planning to help select the optimal position on the skull for burr hole (in humans) or chamber (in monkeys) placement to maximize the likelihood of complete microelectrode and DBS coverage of the intended anatomical target. Intra-operatively, Cicerone allows entry of the stereotactic microdrive coordinates and MER data, enabling real-time interactive visualization of the electrode location in 3D relative to the surrounding neuroanatomy and neurophysiology. In addition, the software enables prediction of the VTA generated by DBS for a range of electrode trajectories and tip locations. In turn, the neurosurgeon can use the combination of anatomical (MRI/CT/3D brain atlas), neurophysiological (MER), and electrical (DBS VTA) data to optimize the placement of the DBS electrode prior to permanent implantation.
Nanofabrication: Principles to Laboratory Practice

This book is designed to introduce typical cleanroom processes, techniques, and their fundamental principles. It is written for the practicing scientist or engineer, with a focus on being able to transition the information from the book to the laboratory. Basic theory such as electromagnetics and electrochemistry is described in as much depth as necessary to understand and explain the current practice and their limitations. Examples from various areas of interest will be covered, such as the fabrication of photonic devices including photo detectors, waveguides, and optical coatings, which are not commonly found in other fabrication texts.
Convolutional Neural Networks Based Ball Detection in Tennis Games

In recent years sport video research has gained a steady interest among the scientific community. The large amount of video data available from broadcast transmissions and from dedicated camera setups, and the need of extracting meaningful information from data, pose significant research challenges. Hence, computer vision and machine learning are essential for enabling automated or semi-automated processing of big data in sports. Although sports are diverse enough to present unique challenges on their own, most of them share the need to identify active entities such as ball or players. In this paper, an innovative deep learning approach to the identification of the ball in tennis context is presented. The work exploits the potential of a convolutional neural network classifier to decide whether a ball is being observed in a single frame, overcoming the typical issues that can occur dealing with classical approaches on long video sequences (e.g. illumination changes and flickering issues). Experiments on real data confirm the validity of the proposed approach that achieves 98.77% accuracy and suggest its implementation and integration at a larger scale in more complex vision systems.
LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance.

Targeting autophagy in cancer cells and in the tumor microenvironment are current goals of cancer therapy. However, components of canonical autophagy play roles in other biological processes, adding complexity to this goal. One such alternative function of autophagy proteins is LC3-associated phagocytosis (LAP), which functions in phagosome maturation and subsequent signaling events. Here, we show that impairment of LAP in the myeloid compartment, rather than canonical autophagy, induces control of tumor growth by tumor-associated macrophages (TAM) upon phagocytosis of dying tumor cells. Single-cell RNA sequencing (RNA-seq) analysis revealed that defects in LAP induce pro-inflammatory gene expression and trigger STING-mediated type I interferon responses in TAM. We found that the anti-tumor effects of LAP impairment require tumor-infiltrating T cells, dependent upon STING and the type I interferon response. Therefore, autophagy proteins in the myeloid cells of the tumor microenvironment contribute to immune suppression of T lymphocytes by effecting LAP.
Sleep apnea screening is uncommon after stroke.

Abstract Objective/Background To assess (1) pre and post-stroke screening for sleep apnea (SA) within a population-based study without an academic medical center, and (2) ethnic differences in post-stroke sleep apnea screening among Mexican Americans (MAs) and non-Hispanic whites (NHWs). Patients/Methods MAs and NHWs with stroke in the Brain Attack Surveillance in Corpus Christi project (2011–2015) were interviewed shortly after stroke about the pre-stroke period, and again at approximately 90 days after stroke in reference to the post-stroke period. Questions included whether any clinical provider directly asked about snoring or daytime sleepiness or had offered polysomnography. Logistic regression tested the association between these outcomes and ethnicity both unadjusted and adjusted for potential confounders. Results Among 981 participants, 63% were MA. MAs in comparison to NHWs were younger, had a higher prevalence of hypertension, diabetes, and never smoking, a higher body mass index, and a lower prevalence of atrial fibrillation. Only 17% reported having been offered SA diagnostic testing pre-stroke, without a difference by ethnicity. In the post-stroke period, only 50 (5%) participants reported being directly queried about snoring; 86 (9%) reported being directly queried about sleepiness; and 55 (6%) reported having been offered polysomnography. No ethnic differences were found for these three outcomes, in unadjusted or adjusted analyses. Conclusions Screening for classic symptoms of SA, and formal testing for SA, are rare within the first 90 days after stroke, for both MAs and NHWs. Provider education is needed to raise awareness that SA affects most patients after stroke and is associated with poor outcomes.
Diagnosis and Treatment of Primary Headache Disorders in Older Adults.

Objectives To provide a unique perspective on geriatric headache and a number of novel treatment options that are not well known outside of the headache literature. Design Review of the most current and relevant headache literature for practitioners specializing in geriatric care. Results Evaluation and management of headache disorders in older adults requires an understanding of the underlying pathophysiology and how it relates to age‐related physiological changes. To treat headache disorders in general, the appropriate diagnosis must first be established, and treatment of headaches in elderly adults poses unique challenges, including potential polypharmacy, medical comorbidities, and physiological changes associated with aging. Conclusion The purpose of this review is to provide a guide to and perspective on the challenges inherent in treating headaches in older adults. J Am Geriatr Soc 66:2408–2416, 2018.
Terror in the dirt: Sensory determinants of host seeking in soil-transmitted mammalian-parasitic nematodes

Infection with gastrointestinal parasitic nematodes is a major cause of chronic morbidity and economic burden around the world, particularly in low-resource settings. Some parasitic nematode species, including the human-parasitic threadworm Strongyloides stercoralis and human-parasitic hookworms in the genera Ancylostoma and Necator, feature a soil-dwelling infective larval stage that seeks out hosts for infection using a variety of host-emitted sensory cues. Here, we review our current understanding of the behavioral responses of soil-dwelling infective larvae to host-emitted sensory cues, and the molecular and cellular mechanisms that mediate these responses. We also discuss the development of methods for transgenesis and CRISPR/Cas9-mediated targeted mutagenesis in Strongyloides stercoralis and the closely related rat parasite Strongyloides ratti. These methods have established S. stercoralis and S. ratti as genetic model systems for gastrointestinal parasitic nematodes and are enabling more detailed investigations into the neural mechanisms that underlie the sensory-driven behaviors of this medically and economically important class of parasites.
Efficient Synthetic Methodology for the Construction of Dihydronaphthalene and Benzosuberene Molecular Frameworks.

Abstract Benzosuberene analogues (1 and 2) and dihydronaphthalene analogues (3 and 4) function as potent inhibitors of tubulin polymerization, demonstrate pronounced cytotoxicity (low nM to pM range) against human cancer cell lines, and are promising vascular disrupting agents (VDAs). As such, these compounds represent lead anticancer agents with potential translatability towards the clinic. Methodology previously established by us (and others) facilitated synthetic access to a variety of structural and functional group modifications necessary to explore structure activity relationship considerations directed towards the development of these (and related) molecules as potential therapeutic agents. During the course of these studies it became apparent that the availability of synthetic methodology to facilitate direct conversion of the phenolic-based compounds to their corresponding aniline congeners would be beneficial. Accordingly, modified synthetic routes toward these target phenols (benzosuberene 1 and dihydronaphthalene 3) were developed in order to improve scalability and overall yield [45-57% (1) and 32% (3)]. Moreover, benzosuberene-based phenolic analogue 1 and separately dihydronaphthalene-based phenolic analogue 3 were successfully converted into their corresponding aniline analogues 2 and 4 in good yield (>60% over three steps) using a palladium catalyzed amination reaction.
Is Locker Room Talk Really Just Talk? An Analysis of Normative Sexual Talk and Behavior

Current sexual violence prevention initiatives have focused on addressing and changing societal norms that are supportive of sexual assault. One area of focus has been the way in which people descr...
Functional and structural similarities of D7 proteins in the independently-evolved salivary secretions of sand flies and mosquitoes

The habit of blood feeding evolved independently in many insect orders of families. Sand flies and mosquitoes belong to separate lineages of blood-feeding Diptera and are thus considered to have evolved the trait independently. Because of this, sand fly salivary proteins differ structurally from those of mosquitoes, and orthologous groups are nearly impossible to define. An exception is the long-form D7-like proteins that show conservation with their mosquito counterparts of numerous residues associated with the N-terminal domain binding pocket. In mosquitoes, this pocket is responsible for the scavenging of proinflammatory cysteinyl leukotrienes and thromboxanes at the feeding site. Here we show that long-form D7 proteins AGE83092 and ABI15936 from the sand fly species, Phlebotomus papatasi and P. duboscqi, respectively, inhibit the activation of platelets by collagen and the thromboxane A2 analog U46619. Using isothermal titration calorimetry, we also demonstrate direct binding of U46619 and cysteinyl leukotrienes C4, D4 and E4 to the P. papatasi protein. The crystal structure of P. duboscqi ABI15936 was determined and found to contain two domains oriented similarly to those of the mosquito proteins. The N-terminal domain contains an apparent eicosanoid binding pocket. The C-terminal domain is smaller in overall size than in the mosquito D7s and is missing some helical elements. Consequently, it does not contain an obvious internal binding pocket for small-molecule ligands that bind to many mosquito D7s. Structural similarities indicate that mosquito and sand fly D7 proteins have evolved from similar progenitors, but phylogenetics and differences in intron/exon structure suggest that they may have acquired the ability to bind vertebrate eicosanoids independently, indicating a convergent evolution scenario.
Diagnostic modalities and nonoperative treatment of lumbar spinal stenosis

Abstract Lumbar spinal stenosis is a common and disabling condition with increasing prevalence in the United States. It is seen in the setting of degenerative lumbar pathology such as degenerative disc disease, spondylolisthesis or degenerative scoliosis and typically results in symptoms of neurogenic claudication – pain in the buttocks or legs that occurs with walking or standing and resolves with sitting or lumbar flexion. While diagnosis can typically be made with a thorough history and physical exam, functional tests such as walking exercise treadmill protocols can be used to increase specificity. Plain radiography with flexion-extension views are the initial imaging modality and demonstrate alignment, instability, bone density, and overall degenerative findings. Magnetic resonance imaging (MRI) is the imaging test of choice since it provides excellent detail of the bony anatomy as well as neural elements without the use of ionizing radiation. Canal cross-sectional area less than 100 to 130 mm2 is generally the threshold for central stenosis, whereas a lateral recess height ≤ 2 mm, lateral recess depth ≤ 3 mm, or a lateral recess angle
Wearing Divine Words: In Life and Death

AbstractThe present paper writes a biography of the silver amulets discovered at the mortuary site of Ketef Hinnom in Jerusalem. While past studies have focused upon the content of the inscriptions...
Gas chromatographic analysis of amino acids as the N-heptafluorobutyryl isobutyl esters

The N-heptafluorobutyryl isobutyl derivatives of proteic amino acids are well resolved by gas chromatography and form the basis of a convenient, rapid assay. The derivatives are prepared by acid-catalyzed esterification at 120 degrees C for 20 min in 3N HCl-isobutanol followed by acylation with heptafluorobutyric anhydride at 150 degrees C for 10 min. The reaction sequence is performed without any transfers or extractions and thus is compatible with microscale analysis. A complete proteic amino acid profile can be completed in less than 20 min by using a packed column or less than 10 min by using a capillary column in combination with an elevated oven temperature program rate. Physiological sample matrixes, which frequently contain a complex mixture of components, and thus require maximum resolution, can be assayed in less than 1 h using a program rate of 4 degrees C/min. A capillary column is recommended for this application. Capillary column chromatography, in combination with a nitrogen-specific detector, is useful for identifying and assaying nonproteic amino acids in physiological sample matrixes. Frequently, a prior cleanup of the sample can be avoided.
The Stavropol’ riot: emerging civil culture and its limits

ABSTRACTRacial and ethnic violence is widespread in the West, including the USA, and is hardly a specific attribute of post-Soviet Russia. It is not caused by post-Soviet Russia’s unwillingness to ...
Conformational flexibility of adenine riboswitch aptamer in apo and bound states using NMR and an X-ray free electron laser

Riboswitches are structured cis-regulators mainly found in the untranslated regions of messenger RNA. The aptamer domain of a riboswitch serves as a sensor for its ligand, the binding of which triggers conformational changes that regulate the behavior of its expression platform. As a model system for understanding riboswitch structures and functions, the add adenine riboswitch has been studied extensively. However, there is a need for further investigation of the conformational dynamics of the aptamer in light of the recent real-time crystallographic study at room temperature (RT) using an X-ray free electron laser (XFEL) and femtosecond X-ray crystallography (SFX). Herein, we investigate the conformational motions of the add adenine riboswitch aptamer domain, in the presence or absence of adenine, using nuclear magnetic resonance relaxation measurements and analysis of RT atomic displacement factors (B-factors). In the absence of ligand, the P1 duplex undergoes a fast exchange where the overall molecule exhibits a motion at kex ~ 319 s−1, based on imino signals. In the presence of ligand, the P1 duplex adopts a highly ordered conformation, with kex~ 83 s−1, similar to the global motion of the molecule, excluding the loops and binding pocket, at 84 s−1. The µs–ms motions in both the apo and bound states are consistent with RT B-factors. Reduced spatial atomic fluctuation, ~ 50%, in P1 upon ligand binding coincides with significantly attenuated temporal dynamic exchanges. The binding pocket is structured in the absence or presence of ligand, as evidenced by relatively low and similar RT B-factors. Therefore, despite the dramatic rearrangement of the binding pocket, those residues exhibit similar spatial thermal fluctuation before and after binding.
Abortion patients' preferences for care and experiences accessing services in Louisiana.

Abstract Objective The objective was to compare abortion patients' expectations and preferences for care with their experiences accessing services in Louisiana where there are numerous restrictive abortion laws. Study design Between June 2018 and January 2019, we conducted in-depth interviews with 35 English-speaking Louisiana residents who were ≥ 18 years of age and seeking care from the three in-state facilities to explore their perspectives and experiences locating, obtaining and paying for abortion services. We analyzed interview transcripts using a theme-based approach and categorized themes into dimensions of health care access: availability/accessibility, accommodation, acceptability and affordability. Results Participants were surprised to learn that there were so few facilities providing abortion, which required some of them to drive between 1 and 3 h to the nearest clinic. Many were unable to schedule their visits at a convenient time or obtain care as early in pregnancy as desired because the next available appointment was often a week or more away. Protestor activity and congested waiting rooms did not provide most patients their desired level of privacy, but participants expressed diverse views about other approaches to care that would maintain their confidentiality. To pay for an unplanned health care expense that was not covered by insurance, many participants deferred paying monthly bills and borrowed money, which contributed to financial hardships and additional delays in care. Conclusions Many Louisiana abortion patients' expectations and preferences for care are not being met across multiple dimensions of health care access assessed in this study, and the state's highly regulated policy environment may limit options for tailoring services to patients' needs. Implications Abortion patients in Louisiana value accessible, timely, private and affordable services, but a constrained network of providers and medically unnecessary requirements make it difficult for them to obtain patient-centered care. Federal- and state-level policy changes, as well as local initiatives, could ensure abortion patients have access to quality, evidence-based services.
Lack of utility of tracheal aspirates in the management of suspected pneumonia in intubated neonates.

Objectives To evaluate the utility of tracheal aspirates in suspected pneumonia in intubated neonates and to measure the burden of antibiotic use associated with a positive tracheal aspirate culture. Design Retrospective cohort study between January 2016 and December 2017. Setting A level IV neonatal intensive care unit (NICU). Patients Intubated patients with a tracheal aspirate culture. Methods Data on temporally associated clinical measures of illness, laboratory and radiographic testing, and clinical demographic information were analyzed. Results Positive tracheal aspirate cultures were associated with lower birth weight and a normal immature to total neutrophil ratio (I/T ratio). Positive tracheal aspirates were not significantly associated with clinical, laboratory, or radiographic markers used in clinical practice to screen for infection. Despite the lack of positive clinical associations, a positive tracheal aspirate culture was associated with increased risk of prolonged antibiotic exposure. Conclusion These findings suggest that positive tracheal aspirates do not always represent clinical infection and may result in unnecessary antibiotic exposure.
The psychological speciesism of humanism

Humanists argue for assigning the highest moral status to all humans over any non-humans directly or indirectly on the basis of uniquely superior human cognitive abilities. They may also claim that humanism is the strongest position from which to combat racism, sexism, and other forms of within-species discrimination. I argue that changing conceptual foundations in comparative research and discoveries of advanced cognition in many non-human species reveal humanism’s psychological speciesism and its similarity with common justifications of within-species discrimination.
Expression in Escherichia Coli, Purification, and Functional Reconstitution of Human Steroid 5α-Reductases.

The potent androgen 5α-dihydrotestosterone irreversibly derives from testosterone via the activity of steroid 5α-reductases (5αRs). The major 5αR isoforms in most species, 5αR1 and 5αR2, have not been purified to homogeneity. We report here the heterologous expression of polyhistidine-tagged, codon-optimized human 5αR1 and 5αR2 cDNAs in Escherichia coli. A combination of the nonionic detergents Triton X-100 and Nonidet P-40 enabled solubilization of these extremely hydrophobic integral membrane proteins and facilitated purification with affinity and cation-exchange chromatography methods. For functional reconstitution, we incorporated the purified isoenzymes into Triton X-100-saturated dioleoylphosphatidylcholine liposomes and removed excess detergent with polystyrene beads. Kinetic studies indicated that the 2 isozymes differ in biochemical properties, with 5αR2 having a lower apparent Km for testosterone, androstenedione, progesterone, and 17-hydroxyprogesterone than 5αR1; however, 5αR1 had a greater capacity for steroid conversion, as reflected by a higher Vmax than 5αR2. Both enzymes preferred progesterone as substrate over other steroids, and the catalytic efficiency of purified reconstituted 5αR2 exhibited a sharp pH optimum at pH 5. Intriguingly, we found that the prostate-cancer drug-metabolite 3-keto-∆ 4-abiraterone is metabolized by 5αR1 but not 5αR2, which may serve as a structural basis for isoform selectivity and inhibitor design. The functional characterization results with the purified reconstituted isoenzymes paralleled trends obtained with HEK-293 cell lines stably expressing native 5αR1 and 5αR2. Access to purified human 5αR1 and 5αR2 will advance studies of these important enzymes and might help to clarify their contributions to steroid anabolism and catabolism.
Self-Silencing and Online Learning

Social influences play a large role in legal education, and they may lead to self-silencing, group polarization, hidden profiles, and cascade effects. In some cases, class discussion may converge on a view that is, in fact, supported by only a minority of students, who do not hear what others actually think or have to say. In other cases, the view is supported by a majority, but uninformed by the minority or minorities. The result can be a failure to take advantage of the information, experiences, or perspectives that students actually have. Given a certain distribution of social norms, or bad luck, conservative students might be silenced; the same is true of students with certain religious convictions, libertarian students, students with far-left views, female students, and students of color. Online learning might be designed or used in such a way as to reduce the relevant risks.
Controlling Ion Coordination Structure and Diffusion Kinetics for Optimized Electrode-Electrolyte Interphases and High-Performance Si Anodes

The cycling performance of batteries is largely determined by the electrode-electrolyte interphase associated with the chemical and electrochemical properties of electrolyte salts and solvents. In ...
The grounds of our freedom

Frankfurt’s ‘Alternate Possibilities and Moral Responsibility’ broke with the tradition of understanding the kind of freedom required for responsibility in terms of alternative possibilities. At th...
PD-1 and LAG-3 blockade improve anti-tumor vaccine efficacy.

Concurrent blockade of different checkpoint receptors, notably PD-1 and CTLA-4, elicits greater anti-tumor activity for some tumor types, and the combination of different checkpoint receptor inhibi...
Including Atmospheric Extinction in a Performance Evaluation of a Fixed Grid of Solar Panels

Solar power is being used to satisfy a higher and higher percentage of our energy needs. We must be able to evaluate the performance of the hardware. Here we present an analysis of the performance of a fixed grid of 13 solar panels installed in the spring of 2021. We confirm that the power output is linearly proportional to the cosine of the angle of the incidence of sunlight with respect to the vector perpendicular to the panels. However, in order to confirm this, we need to consider the dimming effect of the Earth's atmosphere on the intensity of the Sun's light, which is to say we need to rely on astronomical photometric methods. We find a weighted mean value of 0.168 +/- 0.007 mag/airmass for the extinction term, which corresponds to the sea level value at a wavelength of about 0.76 microns. As the efficiency of the solar panels is expected to degrade slowly over time, the data presented here provide a baseline for comparison to the future performance of the system.
Isolation of Nuclei from Mouse Dorsal Root Ganglia for Single-nucleus Genomics

Primary somatosensory neurons, whose cell bodies reside in the dorsal root ganglion (DRG) and trigeminal ganglion, are specialized to transmit sensory information from the periphery to the central nervous system. Our molecular understanding of peripheral sensory neurons has been limited by both their heterogeneity and low abundance compared with non-neuronal cell types in sensory ganglia. We describe a protocol to isolate nuclei from mouse DRGs using iodixanol density gradient centrifugation, which enriches for neuronal nuclei while still sampling non-neuronal cells such as satellite glia and Schwann cells. This protocol is compatible with a range of downstream applications such as single-nucleus transcriptional and epigenomic assays.
El turismo y los inicios de una industria en Chile (1910-1950)

espanolEn este articulo se reconstruyen, de manera exploratoria, los antecedentes estadisticos del desarrollo del turismo en Chile entre 1910 y 1950, que permiten dimensionar sus alcances como actividad economica importante. Se parte del supuesto de que los estudios historicos sobre la materia han privilegiado enfoques socioculturales para analizar el fenomeno turistico, dando por supuesto muchas veces la existencia de una oferta y demanda turisticas, de una politica sobre la materia y de un mercado laboral atractivo para desempenarse en el. A traves de la recopilacion de informacion proveniente de guias y folletos turisticos, leyes y reglamentos, anuarios estadisticos, entre otros, se busca dimensionar los alcances reales que tuvo el turismo como actividad economica, lo que hizo posible la formulacion temprana de una politica de fomento turistico por parte del Estado chileno desde fines de la decada de 1920. EnglishThis article reconstructs in an exploratory way the statistical background of the development of tourism in Chile in the first decades of the twentieth century that allows to dimension its scope as an important economic activity. It is assumed that historical studies on the subject have privileged socio-cultural approaches to analyze the tourist phenomenon, often assuming the existence of a tourist offer and demand, a policy on the subject and an attractive labor market. Through the collection of information from tourist guides and brochures, laws and regulations, statistical yearbooks, among others, it seeks to measure the real scope of tourism as an economic activity, which made the early formulation of a tourism promotion policy possible by the Chilean State since the late 1920s.
An audit and feedback system for effective quality improvement in head and neck surgery: Can we become better surgeons?

Background We have established an evaluation system for measuring physician performance. We aimed to determine whether initial evaluation with surgeon feedback improved subsequent performance.
Adenosine decreases action potential duration by modulation of A- current in rat locus coeruleus neurons

The possibility that adenosine modulates voltage-dependent conductances in locus coeruleus neurons was investigated in current-clamp and voltage-clamp experiments in a totally submerged rat brain slice preparation. Adenosine (100 microM) reduced the duration of control action potentials and action potentials prolonged by 1 mM barium. Adenosine (100 microM) also reduced the amplitude and slightly reduced the duration of TTX-resistant "calcium" action potentials. Action potential duration was also reduced by the adenosine receptor agonist 2-chloroadenosine in a concentration-dependent manner and the adenosine-induced reduction of action potential duration was blocked by the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline, indicating that this action of adenosine is mediated by an adenosine receptor. The adenosine-induced reduction of action potential duration persisted in the presence of externally applied tetraethylammonium ion (6 mM) and cesium (3 mM). By contrast, adenosine did not reduce the duration of the action potential in the presence of 500 microM 4-aminopyridine (4-AP). Furthermore, 4-AP (30 microM) blocked the adenosine-induced reduction of action potential duration recorded in the presence of 1 mM barium. These data suggested that adenosine may be acting on the voltage-dependent, 4-AP-sensitive potassium current, IA. Single-electrode voltage clamp was used to study IA directly. IA was activated by depolarizing voltage pulses from a hyperpolarized holding potential and was blocked by 1 mM 4-AP. Adenosine (300 microM) enhanced IA by shifting the steady-state inactivation curve in the depolarizing direction.(ABSTRACT TRUNCATED AT 250 WORDS)
Airframe Technology for Energy Efficient Transport Aircraft

NASA has initiated a comprehensive Aircraft Energy Efficiency Program which is concerned with the development of approaches for reducing fuel consumption in new aircraft of the 1980-2000 time period. A review is presented of the airframe technologies selected for emphasis in the NASA program, taking into account an evaluation of their potential for reducing transport direct operating costs through fuel efficiency. Attention is given to the importance of fuel efficiency, the impact of advanced technology, advanced composite structures, the NASA composite primary structures program, advanced aerodynamics and active controls, supercritical wing geometry, active load and flutter control, and aspects of laminar flow control.
Adaptation of TCR Repertoires to Self-Peptides in Regulatory and Nonregulatory CD4+ T Cells

Currently, it is not understood how the specificity of the TCR guides CD4(+) T cells into the conventional lineage (Tconv) vs directing them to become regulatory (Treg) cells defined by the Foxp3 transcription factor. To address this question, we made use of the "Limited" (LTD) mouse, which has a restricted TCR repertoire with a fixed TCRbeta chain and a TCRalpha chain minilocus. The TCR repertoires of Tconv and Treg cells were equally broad, were distinct, yet overlapped significantly, representing a less strict partition than previously seen between CD4 and CD8 T cells. As a group, the CDR3alpha motifs showed a significant trend to higher positive charge in Treg than in Tconv cells. The Tconv and Treg repertoires were both reshaped between thymus and periphery. Reducing the array of peptides presented by MHC class II molecules by introducing the H2-DM(o/o) mutation into the LTD mouse led to parallel shifts in the repertoires of Tconv and Treg cells. In both cases, the CDR3alpha elements were entirely different and strikingly shortened, relative to normal LTD mice. These peculiar sequences conferred reactivity to wild-type MHC class II complexes and were excluded from the normal repertoire, even among Treg cells, indicating that some forms of self-reactivity are incompatible with selection into the Treg lineage. In conclusion, the Treg repertoire is broad, with distinct composition and characteristics, yet significantly overlapping and sharing structural constraints with the repertoire of conventional CD4(+) T cells.
Impact of a point system program in increasing fruit and vegetable consumption among university employees (1021.12)

The purpose of this pilot study was to determine the effectiveness of “Colorful choices,™” a competitive, incentive-based program aimed at improving fruit and vegetable consumption over a 4-week pe...
Tn7: smarter than we thought.

A notable feature of transposable elements — segments of DNA that can move from one position to another in genomes — is that they are highly prevalent, despite the fact that their translocation can result in mutation. The bacterial transposon Tn7 uses an elaborate system of target-site selection pathways that favours the dispersal of Tn7 in diverse hosts as well as minimizing its negative effects.
The Interaction of Radio Sources and X-ray-Emitting Gas in Cooling Flows

Recent observations of the interactions between radio sources and the X-ray-emitting gas in cooling flows in the cores of clusters of galaxies are reviewed. The radio sources inflate bubbles in the X-ray gas, which then rise buoyantly outward in the clusters transporting energy to the intracluster medium (ICM). The bright rims of gas around the radio bubbles are cool, rather than hot, and do not show signs of being strongly shocked. Energy deposited into the ICM over the lifetime of a cluster through several outbursts of a radio source helps to account for at least some of the gas that is missing in cooling flows at low temperatures.