cssi/SciSciGPT-SciSciNet huggingface dataset:
Monitoring infiltration in 3D using multi-channel ground-penetrating radar

Summary A constant rate infiltration experiment was conducted in a homogeneous sand tank and monitored with time-lapse multi-channel ground-penetrating radar (GPR) to observe patterns associated with wetting fronts and dynamic hydrologic conditions. The tank measures 4 m x 4 m x 2 m and is filled to a depth of 0.60m with medium-grained river sand. The tank is equipped with 16 individual drainage cells (1 m x 1 m) and two centrally located soil moisture probes embedded at depths of 0.1 m and 0.25 m which logged soil moisture at ten second intervals. An irrigation grid controlled with a peristaltic pump was set to a constant flux rate of 0.08 cm/min while the GPR data was collected at 16 representative times over the course of the experiment. At each measurement time two swaths of data were collected over the length of the tank, with each swath consisting of sixteen channels of 500 MHz radar data at four different offsets (7 lines at 0.25 m, 4 lines at 0.42 m, 3 lines at 0.62 m, and 1 line at 0.84 m). The unprocessed GPR data shows the development of a heterogeneous wetting front indicating non-uniform flow occurred within the tank. At early times, the wetting front reflection is coincident with the groundwave, however, as the experiment progresses the wetting front reflection propagates downward and appears to develop a preferred direction. While the GPR data capture the overall nonuniform movement of the wetting front, questions remain about the detailed heterogeneities associated with the wetting front. For example, diffractions observed along the wetting front reflection provide evidence of fingering. Further data analysis and processing of the multi-channel GPR will lead to improved images of the complex behavior along the wetting front and improved insight into preferential flow behaviors in the vadose zone.
Apparatus for Testing Rotating Heat Pipes

*† ‡ A test apparatus, that will be used to study the heat transfer performance of rotating heat pipes, has been designed and built. The apparatus allows for simultaneous testing of a pair of crank-shaped rotating heat pipes operating near room temperature. The test rig is designed to support heat pipes with an on-axis rotating condenser section, an off-axis eccentrically rotating evaporator section, and a curved adiabatic section. Due to the length of the heat pipes (55”), the distance from the axis of rotation to the off-axis evaporator section (9.5”), and the maximum rotation speed (5500 rpm), care had to be taken in the design of a substantial support structure for the heat pipes, the selection of a drive system, and the design of the mounting frame. These design issues, as well as safety considerations associated with the test apparatus, are discussed here. Preliminary test data for stationary and low-speed tests are also presented.
Novel Therapeutics for Diabetes: Uptake, Usage Trends, and Comparative Effectiveness

The number of available therapies for treating type 2 diabetes has grown considerably in recent years. This growth has been fueled by availability of newer medications, whose benefits and risks have not been fully established. In this study, we review and synthesize the existing literature on the uptake, efficacy, safety, and cost-effectiveness of novel antidiabetic agents. Specifically, we focus on three drug classes that were introduced in the market recently: thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Not surprisingly, we find that the usage trends reflect the efficacy and safety profile of these novel drugs. The use of TZDs increased initially but decreased after a black-box warning was issued for rosiglitazone in 2007 that highlighted the cardiovascular risks associated with using the drug. Conversely, DPP-4 inhibitors and GLP-1 receptor agonists gained market shares due to their efficacy in glycemic control as an add-on treatment to metformin. DPP-4 inhibitors were the most commonly prescribed agents among the three novel drug classes, likely because they are relatively less expensive, have better safety profile, are administered orally, and are weight neutral. Sitagliptin was the most preferred DPP-4 inhibitor. The level of evidence on the comparative effectiveness, safety, and cost implications of using novel antidiabetic agents remains low and further studies with long-term follow-ups are needed.
Investigation of the Change of SF_6 Decomposition Products with Discharge Condition

Measurement and analysis of the SF6 decomposition products is important to safe operation of electrical equipment.A simulated discharge test method for SF6 insulated electrical equipment is established,and SF6 decomposition products under different simulated discharge conditions are hence investigated via gas chromatography,ion chromatography and detector tube method with regard to the generation process and volume fraction of the products to find the characteristic products which can characterize different discharge faults.This study provides theory and method for judging SF6 insulated electrical equipment’s internal state by quantitative detection of SF6 decomposition products,which may be of significance in early diagnosis and prediction of abrupt faults of the equipment due to discharge.
Approximation-tolerant model-based compressive sensing

The goal of sparse recovery is to recover a k-sparse signal x e Rn from (possibly noisy) linear measurements of the form y = Ax, where A e Rmxn describes the measurement process. Standard results in compressive sensing show that it is possible to recover the signal x from m = O(k log(n/k)) measurements, and that this bound is tight. The framework of model-based compressive sensing [BCDH10] overcomes the lower bound and reduces the number of measurements further to O(k) by limiting the supports of x to a subset M of the (nk) possible supports. This has led to many measurement-efficient algorithms for a wide variety of signal models, including block-sparsity and tree-sparsity.Unfortunately, extending the framework to other, more general models has been stymied by the following obstacle: for the framework to apply, one needs an algorithm that, given a signal x, solves the following optimization problem exactly:[EQUATION](here x[n]\Ω denotes the projection of x on coordinates not in Ω). However, an approximation algorithm for this optimization task is not sufficient. Since many problems of this form are not known to have exact polynomial-time algorithms, this requirement poses an obstacle for extending the framework to a richer class of models.In this paper, we remove this obstacle and show how to extend the model-based compressive sensing framework so that it requires only approximate solutions to the aforementioned optimization problems. Interestingly, our extension requires the existence of approximation algorithms for both the maximization and the minimization variants of the optimization problem.Further, we apply our framework to the Constrained Earth Mover's Distance (CEMD) model introduced in [SHI13], obtaining a sparse recovery scheme that uses significantly less than O(k log(n/k)) measurements. This is the first non-trivial theoretical bound for this model, since the validation of the approach presented in [SHI13] was purely empirical. The result is obtained by designing a novel approximation algorithm for the maximization version of the problem and proving approximation guarantees for the minimization algorithm described in [SHI13].
Leadless Cardiac Devices—Pacemakers and Implantable Cardioverter-Defibrillators

Since the initial introduction of pacemakers and defibrillators, the rapid growth in microcircuit and battery technology has increased the longevity demands and exposed the vulnerabilities of transvenous leads. Over a half of century later, leadless pacemaker and defibrillation systems are just reaching the clinical arena. Despite the remarkable advantages of leadless pacing systems, the data are still quite limited and broad implementation of these technologies need to occur in a cautious and deliberate fashion as the peri-procedural risks remains high. Two of the three systems, NanostimTM (St. Jude Medical) and Micra Transcatheter Pacing System (Medtronic Inc.), have shown the greatest applicability, although they are currently only limited to single chamber pacing and procedural risks are modest. The WiCSTM-LV system (EBR Systems, Inc.) is anatomically limited and benefits a small subset of patients. Leadless implantable cardioverter-defibrillator (ICD) therapy, the subcutaneous ICD (S-ICD, Cameron Health/Boston Scientific), has demonstrated encouraging short-term safety and efficacy data supporting its use. Since its introduction, modifications to the implant procedure, pre-screening of patients, and programming of the devices have reduced procedural-related complications and inappropriate shocks. The S-ICD is a promising technology, but it is premature to conclude that it will supplant conventional ICDs. At this current time, the S-ICD may benefit select patients, such as those with recurrent bacteremia, vascular access limitations, and who may be prone to transvenous lead failure.
The Relationship Between User Mouse-based Performance And Subjective Usability Assessments:

Objective metrics, such as effectiveness and efficiency, are often considered to be the best website usability measurements. User performance metrics that can be collected remotely, such as mouse c...
Identification of Distinct Cytokine and Chemokine Clusters That Correlate with Outcome In B-Cell Chronic Lymphocytic Leukemia: Implications for Disease Pathogenesis

Abstract Abstract 1368 The growth and accumulation of B-cell chronic lymphocytic leukemia (CLL) cells requires survival and migratory signals supplied by endogenously produced cytokines and chemokines. Multiplex cytokine and chemokine analyses revealed that CCL2, CCL3, CCL4, IL-1b, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12, CXCL9, CXCL11, TNFa, IFNg, IFNa, and IL-17 levels are significantly elevated in the serum of CLL patients (84 total) as compared to healthy age-matched subjects (48 total; p median) versus low ( 21.5 yr; p=0.01), while high serum levels of Clus3 cytokines independently correlated with longer survival times (Clus3HI 21.6 yr versus Clus3LOW 12.5 years; p=0.05). The levels of Clus2 did not correlate with CLL patient survival. Combination analyses revealed that patients with high levels of Clus1 in the absence of Clus2 had significantly shorter survival times (10 yr) relative to patients with high levels of Clus1 cytokines in the presence of Clus2 (10yr vs 16yr; p=0.0018). In contrast, there was no significant difference between survival in patients with high levels of Clus1 in either the presence or absence of Clus3HI. Taken together, this suggests a beneficial modulatory role of cluster 2 cytokines. CONCLUSIONS: Application of multiplex bead immunoassays has allowed us to identify a set of cytokines and chemokines that are elevated within the context of CLL, to rank these secreted factors with respect to their importance in discriminating CLL from controls, and to identify those factors whose expression correlates with CLL disease prognosis. Complementary bioinformatics analysis allowed identification of three distinct clusters of cytokines and chemokines whose integrated expression levels reflect different CLL patient outcomes. Disclosures: No relevant conflicts of interest to declare.
Distributed quickest detection with optional observations at the fusion center

In this paper, decentralized change point detection problem with optional observations at the fusion center is considered. In the model considered, there are two sensors: a peripheral sensor and a coordinating sensor. At each time, the peripheral sensor decides whether to stop and send an alarm to the coordinating sensor or to continue making observations. Once the coordinating sensor receives an alarm from the peripheral sensor, the coordinate sensor has the option to take its own observations or to stop immediately and raise a final alarm. Under a Bayesian setup, using tools from multiple optimal stopping time theory, we obtain optimal decision rules for both the peripheral sensor and the coordinating sensor that achieve a desirable tradeoff between the detection delay and false alarm.
Shape Analysis and Deployment of the ExaVolt Antenna

The ExaVolt Antenna (EVA) is the next generation balloon-borne ultra-high energy (UHE) particle observatory under development for NASA’s suborbital super-pressure balloon program in Antarctica. Unlike a typical mission where the balloon lifts a gondola that carries the primary scientific instrument, the EVA mission is a first-of-its-kind in that the balloon itself is part of the science instrument. Specifically, a toroidal RF reflector is mounted onto the outside surface of a superpressure balloon (SPB) and a feed antenna is suspended inside the balloon, creating a high-gain antenna system with a synoptic view of the Antarctic ice sheet. The EVA mission presents a number of technical challenges. For example, can a stowed feed antenna be inserted through an opening in the top-plate? Can the feed antenna be deployed during the ascent? Once float altitude is achieved, how might small shape changes in the balloon shape affect the antenna performance over the life of the EVA mission? The EVA team utilized a combination of testing with a 1/20-scale physical model, mathematical modeling and numerical simulations to probe these and related questions. While the problems are challenging, they are solvable with current technology and expertise. Experiments with a 1/20-scale EVA physical model outline a pathway for inserting a stowed feed into a SPB. Analysis indicates the EVA system will ascend, deploy and assume a stable configuration at float altitude. Nominal shape changes in an Antarctic SPB are sufficiently small to allow the use of the surface of the balloon as a high-gain reflector.
Diagnostics, Control and Performance Parameters for the BELLA High Repetition Rate Petawatt Class Laser

A laser system producing controllable and stable pulses with high power and ultrashort duration at high repetition rate is a key component of a high energy laser-plasma accelerator (LPA). Precise characterization and control of laser properties are essential to understanding laser-plasma interactions required to build a 10-GeV class LPA. This paper discusses the diagnostics, control and performance parameters of a 1 Hz, 1 petawatt (PW) class laser at the Berkeley Lab Laser Accelerator (BELLA) facility. The BELLA PW laser provided up to 46 J on target with a 1% level energy fluctuation and 1.3-μrad pointing stability. The spatial profile was measured and optimized by using a camera, wavefront sensor, and deformable mirror (ILAO system). The focus waist was measured to be r0 = 53 μm and the fraction of energy within the circular area defined by the first minimum of the diffraction pattern (r = 67 μm) was 0.75. The temporal profile was controlled via the angle of incidence on a stretcher and a compressor, as well as an acousto-optic programmable dispersive. The temporal pulse shape was measured to be about 33 fs in full width at half maximum (WIZZLER and GRENOUILLE diagnostics). In order to accurately evaluate peak intensity, the energy-normalized peak fluence, and energy-normalized peak power were analyzed for the measured spatial and temporal mode profiles, and were found to be 15 kJ/(cm2 J) with 6% fluctuation (standard deviation) and 25 TW/J with 5% fluctuation for 46-J on-target energy, respectively. This yielded a peak power of 1.2 PW and a peak intensity of 17×1018 W/cm2 with 8% fluctuation. A method to model the pulse shape for arbitrary compressor grating distance with high accuracy was developed. The pulse contrast above the amplified spontaneous emission pedestal was measured by SEQUOIA and found to be better than 109. The first order spatiotemporal couplings (STCs) were measured with GRENOUILLE, and a simulation of the pulse's evolution at the vicinity of the target was presented. A maximum pulse front tilt angle of less than 7 mrad was achieved. The reduction of the peak power caused by the first order STCs was estimated to be less than 1%. The capabilities described in thispaper are essential for generation of high quality electron beams.
In-situ stability control of energy-producing anaerobic biological reactors through novel use of ion exchange fibers

Anaerobic biological treatment of high-strength organic industrial wastes is preferred over aerobic treatment as it produces a methane-rich biogas, has much lower energy requirements, and produces significantly less biosolids. Process stability and reactor failure are of concern, however, for waste streams that exhibit large variations in organic loading, which can cause detrimental pH fluctuations, and that have the potential for accidental input of toxic metals. Here, we demonstrate for the first time that the use of ion exchange fibers (IXFs) can provide passive resilience to these failure modes, without requiring operator oversight or reactive process control via chemical addition. IXFs have the advantage of rapid kinetics due to their small size, and they can be readily inserted and withdrawn as woven mats or porous pillows. This approach is demonstrated here using the weak-acid IXF FIBAN X-1 and the strong-base FIBAN A-1. FIBAN X-1 passively stabilized anaerobic reactors by (i) buffering pH fluctuat...
Systems change to improve tobacco use identification and referral in the chiropractic setting: a pilot study.

Tobacco use remains a leading cause of death and disability in the United States. Health professionals need to address the use of tobacco products by their patients, but chiropractic clinical systems often remain unsupported and underappreciated in their role to facilitate tobacco use cessation. This pilot study tested an intervention to assist a chiropractic community to implement sustainable health systems changes for tobacco use based on U.S. Public Health Service guidelines. Chiropractors were educated on the Ask, Advise, Refer (AAR) approach, provided with ongoing guidance, and followed for six months to assess systems change. The study was conducted from March 2016 to July 2017. Evidence of a systematic process in place to conduct AAR was present in all clinics by the end of the fourth month of the intervention period. Although no clinic had sustained health system change for full AAR, all six of the clinics made progress in the individual AAR components. Furthermore, five clinics achieved sustained system change for the Ask component, as after systems change was achieved, the rate of tobacco user identifications did not drop below 50%. For the Advise component, five clinics succeeded in having individual months of ≥50% of tobacco users being advised, and three clinics achieved the formal definition of systems change. For the Refer component, no clinic achieved system change, although four had individual months of ≥50% of tobacco users being referred. The patient quit rate was 13.3% (n = 15) for the 30-day follow-up and 16.7% (n = 6) for the three-month follow-up. This study demonstrates the feasibility of implementing a health systems change in the chiropractic setting to identify tobacco users, to advise them to quit, and to refer users for cessation services.
Rhetorical Confinement, Contrasting Metaphors, and Cultural Polarities "Yes we can" Meets "Carnage in the cities"

Abstract In this study we contrast metaphors and metaphorical stories in President Trump’s 2017 inaugural address with those of former President Barack Obama’s first inaugural address. We draw on the concept of ‘rhetorical confinement’ (Patterson, 2011) to show how the contrasting life trajectories of the two leaders are reflected in the contrasting themes and tone established by their metaphorical language. We argue that Obama’s rhetorical tone, including his use of metaphors, was at least in part a response to the compound constraints of race and class. In contrast, Trump’s rhetorical tone and use of metaphors reflects and reinforces his image as a political outsider, as a challenge to the constraints of ordinary political discourse. The contrast between the rhetorically confined politeness of Obama’s discourse (lampooned as ‘political correctness’ by many of his opponents) and the unconstrained crudeness of Trump’s discourse (lauded as ‘telling it like it is’) apparently legitimates the open expression of previously suppressed resentments and encourages an extreme rhetoric that is symptomatic of, and may contribute to, the growing polarization in American political discourse.
Effects of lipopolysaccharide-induced inflammation on hypoxia and inflammatory gene expression pathways of the rat testis

Bacterial infection and inflammation of the testis impairs fertility, yet an understanding of inflammatory responses of the testis is incomplete. We are interested in identifying gene pathways involved in the detection and clearance of infectious microbes in the male reproductive tract. In previous studies in our lab focused on hypoxia-responsive genes of the testis, preliminary experiments suggested that genes classically categorized as hypoxia genes are also activated during antimicrobial responses. The purpose of this study was to identify hypoxia and inflammatory gene pathways that contribute to antimicrobial protection of the testis and to consider possible cross-talk and interactions between these pathways. Inflammation was induced in Sprague-Dawley rats using P. aeruginosa or E. coli lipopolysaccharide (LPS). Levels of hypoxia-inducible factor-1 (HIF-1α) protein and nuclear factor kappa B (NF-κB) were measured, and hypoxia and inflammatory gene expression patterns in testis were analyzed by gene expression profiling using real-time quantitative PCR arrays. In LPS-treated rats, HIF-1α protein increased with no change in Hif-1α mRNA. Western Blot analysis also demonstrated no change in NF-κB and inhibitory NFKB alpha (IκBα) protein levels following LPS treatment. Five hypoxia pathway genes (Angptl4, Egr1, Ier3, Pai1, and Glut1), and 11 inflammatory pathway genes (Ccl12, Cc13, Cd14, Cxcl10, Icam1, Il10, Il1b, Il6, Nfkbia, Tlr2, Tnf) up-regulated after 3 h of inflammation. Angptl4, Ccl12, Cc13, Cd14, Egr1, Nfkbia, Tlr2, and Tnf remained elevated at 6 h. Six genes were up-regulated at 6 h only (Bhlhe40, C3, Jak2, Nlrp3, Slc11a1, Tlr1). One gene (Tlr5) was down-regulated after 3 h and no genes at 6 h. Electrophoretic mobility shift assay results suggest a decrease in NF-κB binding activity following LPS treatment. Testicular HIF-1α is up-regulated following LPS-induced inflammation. In contrast to other tissues, in which HIF-1α is up-regulated through transcriptional activation via NF-κB, we conclude that HIF-1α in the testis is not up-regulated through an increase in Hif-1α mRNA or through NF-κB-dependent mechanisms. Hypoxia pathway genes and genes involved in Toll-like receptor (TLR) and cytokine-mediated signaling comprise major functional categories of up-regulated genes, demonstrating that both hypoxia and classic inflammatory pathways are involved in inflammatory responses of the testis.
Pyrolytic lignin from fast pyrolysis bio-oil via cold-water precipitation: Optimal separation conditions and properties

Abstract The paper reports the properties of pyrolytic lignin (PL) separated from a fast pyrolysis bio-oil via cold-water precipitation under various conditions. Three different mixing methods were deployed, including magnetic stirring, high-speed homogenizing and ultrasonication. The results show that the proportion of water in the bio-oil/water mixture plays a significant role in achieving complete bio-oil separation for PL production. In systems with a low water proportion (85%, corresponding to added-water/bio-oil ratio of 4), incomplete separation occurs regardless the stirring conditions. In systems with 95% water (corresponding to added-water/bio-oil ratio of 17), continuous magnetic stirring at a low speed after bio-oil addition (e.g. 750 rpm for 1 h) can be an alternative method to high-speed homogenizing (at 6000 rpm) or even repeated washing process for complete bio-oil separation for PL preparation. The PL samples prepared from these complete separation processes have similar properties in terms of elemental compositions and aromatic structure etc. For the PL samples prepared from incomplete separation in systems with a low water proportion (85%), the PL samples mostly remain in the container and are in a sticky gummy form. Compared to the powder-like PL obtained on filter paper from complete separation, those sticky PL samples have higher yields, lower molecular weights, lower carbon contents and less condensed aromatic ring structures.
Hypocretin Receptor 1 Regulation of Dopamine Neurotransmission and Motivated Behavior

Abstract Hypocretin- (also known as orexin) containing neurons of the lateral hypothalamus project widely throughout the brain and are implicated in a range of behaviors via signaling at hypocretin receptor 1 (HCRTr1) and hypocretin receptor 2. These neurons send a moderate, but influential, projection to the dopaminergic ventral tegmental area which—as part of the mesolimbic dopamine system—is highly implicated in motivated behavior and substance abuse. In this chapter, we will explore the contribution of HCRTr1 to dopamine neurotransmission and its consequential importance to addiction-related processes. Following, we review evidence for HCRTr1 involvement in supporting drug-associated behavior across behavioral models of addiction. We then discuss HCRTr1 regulation of ventral tegmental dopamine neuron activity and its impact on dopamine neurotransmission in the nucleus accumbens, and address hypocretin-dopamine interactions and their effects in females. Finally, we propose that HCRTr1 regulation of dopamine release influences behavioral responses to drug-associated cues.
VESSEL PREPARATION IMPROVES DRUG ELUTING STENT (DES) EXPANSION PARAMETERS VERSUS DIRECT CORONARY STENTING IN NON-COMPLEX LESIONS AS ASSESSED BY HIGH-RESOLUTION OPTICAL COHERENCE TOMOGRAPHY (OCT)

DES may be deployed with or without vessel prep in uncalcified CAD. It is unknown if vessel prep improves DES expansion/apposition vs. high-pressure direct stenting and if the architecture of individual DES platforms impacts expansion. High-resolution OCT is an ideal tool for measuring DES sizing/
The Support, Education, and Advocacy (SEA) Program of Care for Women With Metastatic Breast Cancer: A Nurse-Led Palliative Care Demonstration Program

Background:Women with metastatic breast cancer (MBC) experience unique symptom management and psychosocial needs due to aggressive, yet palliative treatment with a progressive, chronic illness.Obje...
Religion and Its Intersections: Spirituality, Secularism and Religion Among Black Diasporic Communities in Higher Education

AbstractA reinvigorated commitment to the study of religion, spirituality, faith, secularism, meaning-making, purpose, and interfaith dialogue in higher education is evidenced through the productio...
Age-dependent Lidocaine Pharmacokinetics During Lumbar Peridural Anesthesia with Lidocaine Hydrocarbonate or Lidocaine Hydrochloride

Lumbar peridural anesthesia with 20 ml of 2% lidocaine hydrochloride (HCI) or lidocaine hydrocarbonate (CO2) and epinephrine 1:200,000 was administered to 50 men ranging in age from 22 to 78 years. Venous blood samples were obtained over an 8-hour period to determine clearance (CI), half-life (t 1/2), volume of distribution (Vd), and peak concentration. There were no significant pharmacokinetic differences between the two lidocaine salts. Subgroups of patients younger than 40 (n = 9) and older than 55 (n = 33) years were compared. Lidocaine clearance was 33% lower in the older group (0.81 ± 0.30 vs. 0.54 ± 0.15 L/min, p 0.05) in older patients. There was a weak but statistically significant negative correlation between clearance and age for the entire group of 50 patients r = −0.41 (p
Publishing: Academic and University Presses

Since the emergence of the modern university press nearly 150 years ago, these academic publishers have played an essential role in the world of scholarship, not only by making knowledge widely available through the books they publish but also by validating the quality of those books through the process of peer review and by actively engaging with authors to generate ideas for future works. The advent of three relatively new trends – corporate consolidation, globalization, and digitization – has now brought scholarly publishing to a crossroads, and how presses respond to these forces will determine their role in the years to come.
Electric Pulse Pretreatment for Enhanced Lipid Recovery from Chlorella protothecoides

Developing effective, energy-efficient methods to extract lipids from microalgae remains a challenge in bioenergy. This study assesses electric pulse (EP) pretreatments to enhance lipid extraction from Chlorella protothecoides. In tandem with solvent extraction, we applied 10, 50, 100, 200, and 300 60 kV/cm, 60 ns duration EPs or 3, 17, 33, 67, and 100 60 kV/cm, 300 ns duration EPs to match the energy density u applied to the sample for each EP duration. Lipid recovery increased with increasing u for each EP duration until reaching a maximum for 17 300 ns EPs (the second lowest u) and 100 60 ns EPs (the third lowest u) to achieve a 13.3% and 16.1% increase in lipid extraction, respectively. Lipid extraction declined at higher u due to increased cell lysis. The largest net energy released calculated from the difference between the energy available from the extracted lipids and the applied energy of the EPs occurred at the lowest u for each EP duration. Applying trains of 100 μs EPs induced qualitatively similar behavior. These results suggest that a more detailed parametric study may optimize EP parameters for net energy release for specific microalgae and solvents.
Evaluation of Quantitative Relationship Between Target Expression and Antibody-Drug Conjugate Exposure Inside Cancer Cells.

Antibody-drug conjugates (ADCs) employ overexpressed cell surface antigens to deliver cytotoxic payloads inside cancer cells. However, the relationship between target expression and ADC efficacy remains ambiguous. In this manuscript, we have addressed a part of this ambiguity by quantitatively investigating the effect of antigen expression levels on ADC exposure within cancer cells. Trastuzumab-valine-citrulline-monomethyl auristatin E was used as a model ADC, and four different cell lines with diverse levels of human epidermal growth factor receptor 2 (HER2) expression were used as model cells. The pharmacokinetics (PK) of total trastuzumab, released monomethyl auristatin E (MMAE), and total MMAE were measured inside the cells and in the cell culture media following incubation with two different concentrations of ADC. In addition, target expression levels, target internalization rate, and cathepsin B and MDR1 protein concentrations were determined for each cell line. All the PK data were mathematically characterized using a cell-level systems PK model for ADC. It was found that SKBR-3, MDA-MB-453, MCF-7, and MDA-MB-468 cells had ∼800,000, ∼250,000, ∼50,000, and ∼10,000 HER2 receptors per cell, respectively. A strong linear relationship (R2 > 0.9) was observed between HER2 receptor count and released MMAE exposure inside the cancer cells. There was an inverse relationship found between HER2 expression level and internalization rate, and cathepsin B and multidrug resistance protein 1 (MDR1) expression level varied slightly among the cell lines. The PK model was able to simultaneously capture all the PK profiles reasonably well while estimating only two parameters. Our results demonstrate a strong quantitative relationship between antigen expression level and intracellular exposure of ADCs in cancer cells. SIGNIFICANCE STATEMENT In this manuscript, we have demonstrated a strong linear relationship between target expression level and antibody-drug conjugate (ADC) exposure inside cancer cells. We have also shown that this relationship can be accurately captured using the cell-level systems pharmacokinetics model developed for ADCs. Our results indirectly suggest that the lack of relationship between target expression and efficacy of ADC may stem from differences in the pharmacodynamic properties of cancer cells.
Plasma and intracellular pharmacokinetics of tenofovir disoproxil fumarate and emtricitabine in transgender women receiving feminizing hormone therapy.

Background Transwomen have an increased risk of HIV acquisition compared with other adults. Drug-drug interactions between pre-exposure prophylaxis (PrEP) and gender-affirming therapy are cited as a reason for poor PrEP uptake among transwomen. We evaluated plasma tenofovir and emtricitabine pharmacokinetics and their active intracellular anabolites, tenofovir-diphosphate and emtricitabine-triphosphate, in transwomen receiving feminizing hormones. Methods We enrolled HIV-negative transwomen (≥19 years) not receiving PrEP. Participants took oral tenofovir disoproxil fumarate/emtricitabine 300/200 mg daily for 14 days. Plasma was collected at 0 h (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 12 h on day 14 post-tenofovir disoproxil fumarate/emtricitabine dose. The plasma AUC0-24 was calculated using the trapezoidal rule and compared with historical HIV-negative cisgender adults as geometric mean ratios (GMRs, 90% CI). Secondarily, tenofovir-diphosphate and emtricitabine-triphosphate from PBMCs collected at 0 h and 12 h were reported descriptively as geometric means (90% CI). Clinical trials registration: NCT03270969. Results Among 15 transwomen (mean age 32 years), geometric mean tenofovir and emtricitabine plasma AUC0-24 were lower compared with controls: tenofovir, 2.10 versus 2.76 mg·h/L, GMR 0.76 (0.65-0.90), P = 0.01; emtricitabine, 9.15 versus 10.64 mg·h/L, GMR 0.86 (0.75-0.98), P = 0.07. Tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in the literature: 167.1 (146.6-190.5) fmol/106 cells and 15.4 (13.8-17.3) pmol/106 cells, respectively. Conclusions We observed lower plasma tenofovir and emtricitabine concentrations in transwomen compared with historical cisgender adults, yet intracellular tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in PBMCs. Understanding the differences of PrEP pharmacokinetics in plasma and tissue compartments and the resultant impact on efficacy remains important for transwomen.
Microstructural heterogeneity and mechanical anisotropy of 18Ni-330 maraging steel fabricated by selective laser melting: The effect of build orientation and height

Distinguished by a marked combination of high strength and high fracture toughness, 18Ni-300 maraging steel (MS) is widely used for intricate tool and die applications. MS is also amenable to the powder bed fusion additive manufacturing process, providing unique opportunities to make small features and incorporate cooling channels in molds. In this study, tensile test samples were fabricated using selective laser melting to investigate the effects of built height and orientations on the evolution of the microstructure and the mechanical properties of the samples. The microstructure of the as-fabricated samples consists of the primary a-martensite phase and fine cellular microstructure (~0.66–0.83 µm) with the retained austenite ?-phase aggregated at the boundaries of the cells, resulting in an enhanced mechanical performance compared with traditional counterparts under the same condition (without post-heat treatments). Random grain orientations with weak textures are revealed in all samples. The XY-built samples display better tensile performance when compared to the Z-built samples due to the fine grain sizes and the retained ? phase. The bottom of the Z-built sample exhibits a higher hardness than other parts of the sample, which could be attributed to its finer cellular structure.
Time-reversal symmetry breaking with acoustic pumping of nanophotonic circuits

Achieving non-reciprocal light propagation via stimuli that break time-reversal symmetry, without magneto-optics, remains a major challenge for integrated nanophotonic devices. Recently, optomechanical microsystems in which light and vibrational modes are coupled through ponderomotive forces have demonstrated strong non-reciprocal effects through a variety of techniques, but always using optical pumping. None of these approaches has demonstrated bandwidth exceeding that of the mechanical system, and all of them require optical power; these are both fundamental and practical issues. Here, we resolve both challenges by breaking time-reversal symmetry using a two-dimensional acoustic pump that simultaneously provides a non-zero overlap integral for light–sound interaction and also satisfies the necessary phase-matching. We use this technique to produce a non-reciprocal modulator (a frequency shifting isolator) by means of indirect interband scattering. We demonstrate mode conversion asymmetry up to 15 dB and efficiency as high as 17% over a bandwidth exceeding 1 GHz. Time-reversal symmetry is broken via an acoustic pumping scheme enabling demonstration of a frequency shifting optical isolator with 15 dB asymmetry and 1 GHz bandwidth.
COVID-19 and Immigration: Reflections From the Penn State Law Center for Immigrants' Rights Clinic

Since the 2016 Presidential Election, the Center for Immigrants’ Rights Clinic (CIRC) at Penn State Law in University Park has been at the forefront of responding to rapidly changing immigration policies that include the “travel ban,” efforts to end a policy called “DACA”, policies to curb asylum at the southern border, and efforts to more easily exclude international students and scholars. Some of the tools CIRC has used to respond to these changes include easy to understand “fact sheets”, in person and virtual “town halls,” and legal support for individuals fighting deportation or seeking refuge. This essay will use CIRC as a case study to demonstrate how one set of student advocates used the same tools developed over three years of responding to ever-evolving immigration policies to respond to changes surrounding COVID-19. Specifically, we describe CIRC’s responses to changes at international borders, stalemates in immigration detention, expansions to asylum restrictions, and the status of DACA at the Supreme Court. This article explains how the same responses that have long been used to address the current administration's immigration changes can also be used to respond to immigration policy changes resulting from the COVID-19 pandemic. This essay discusses how CIRC responded to each significant immigration policy change arising out of COVID-19, as well as explains how CIRC moved from an in-person to remote platform in spring 2020 alongside many law clinics across the country, shares reflections from those students, and offers lessons that can be drawn for legal education moving forward.
Regional dynamics of fractal dimension of the LV endocardium from cine CT images

We present a method to leverage the high fidelity of CT to quantify regional left ventricular function using topography variation of the endocardium as a surrogate measure of strain. 4DCT images of 10 normal and 10 abnormal subjects, acquired with standard clinical protocols, were used. The topography of the endocardium was characterized by its regional values of fractal dimension (FD), computed using a box-counting algorithm developed in-house. The average FD in each of the 16 American Heart Association segments was calculated for each subject as a function of time over the cardiac cycle. The normal subjects showed a peak systolic percentage change in FD of 5.9% {+/-} 2% in all free-wall segments, while the abnormal cohort experienced a change of 2% {+/-} 1.2% (p < 0.00001). Septal segments, being smooth, did not undergo large changes in FD. Additionally, a principal component analysis was performed on the temporal profiles of FD to highlight the possibility for unsupervised classification of normal and abnormal function. The method developed is free from manual contouring and does not require any feature tracking or registration algorithms. The FD values in the free wall segments correlated well with radial strain and with endocardial regional shortening measurements.
Diaphragm Pacing in Lung Transplant Patients: To Identify and Treat Diaphragm Function Abnormalities

Purpose Lung disease and transplantation can lead to diaphragm dysfunction (DD). Phrenic neuropathy in lung transplants increases morbidity. Diaphragm pacing (DP) improves nerve recovery and prevents ventilator induced diaphragm dysfunction (VIDD). The FDA authorized temporary DP to decrease the burden of mechanical ventilators (MV) during the COVID-19 pandemic. We report the largest experience of DP in lung transplantation. Methods This is a retrospective analysis of an IRB approved prospective, non-randomized interventional experience at a single institution with two DP systems. A chronic DP system was laparoscopically implanted in those with identified (either pre or post-transplant) phrenic nerve injury. Post implantation, diaphragm stimulation ensued and results evaluated radiographically and with diaphragm electromyography (dEMG). Transplant recipients had the temporary DP system implanted percutaneously via their chest incision. Diaphragm activity was monitored with the electrodes and stimulation applied for MV weaning. Results 8 patients utilized DP with no device adverse events. 3 patients with DD, 6 months average post-transplant, had chronic DP implanted. All had evidence of subsequent recovery of diaphragm function. 1 patient had DP pre-transplant for unilateral DD with subsequent diaphragm recovery. At time of unilateral transplant on contralateral side a phrenic nerve injury was identified. DP was used during the recovery. 4 patients underwent implantation of temporary DP electrodes during lung transplant. 2 patients had bilateral dEMG identified post-operatively with uneventful recovery and removal of electrodes. 2 patient had no dEMG activity or movement bilaterally post-operatively. Retrospectively this was a pre-operative condition. 1 recovered diaphragm function at 2 weeks with DP therapy. The 2nd is still undergoing DP. 3 patients with phrenic nerve dysfunction post operatively also had intercostal nerve cryoanalgesia which decreases external intercostal muscles use for respiration. These 3 patients had prolonged ventilation difficulties. Conclusion DP was safely used in lung transplantation in identifying and improving recovery of phrenic nerve injuries and preventing VIDD. Intercostal nerve cryoanalgesia should not be used if there is DD. DP should be considered in all lung transplants for improved outcomes.
The Chicken or the Egg: Causality Between Trade and Innovation

While the literature is quite clear on the association between trade and innovation, there has been little explicit study of the direction of causality. This study uses all patents granted in the USA between 1987 and 1999, assigns them to probable industries of origin and sectors of use, then tests causality with trade flows in those same economic sectors. We run robustness checks on various measures of trade (imports versus exports, volume versus value of trade), and on various measures of innovation (patent counts, patent claims, citation-weighted patents, and patent counts weighted for originality or generality). Results at the aggregate level support the literature’s assumption that imports cause innovation which then leads to exports, but at the industry level, causality is more complicated, running in both directions from imports (or exports) to and from innovation.
Cost-Effectiveness Analysis of Minimally Invasive Trabecular Meshwork Stents with Phacoemulsification.

Purpose To investigate the costs and effects of implanting trabecular meshwork bypass stents during cataract surgery from a societal perspective in the United States. Design Cost-utility analysis using Markov models and efficacy/safety data from published pivotal or randomized control trials (RCTs) of devices investigated. Participants Patients aged 65 years and older with mild to moderate primary open-angle glaucoma with or without visually significant cataract. Methods With the use of Markov models, glaucoma progression through 4 glaucoma states (mild, moderate, advanced, severe/blind) and death were simulated over 35 years. The cohort with cataract entered the model and received cataract surgery with or without device implantation. We included a medication management only reference group to calculate total costs and outcomes for those without cataract. Intraocular pressure (IOP) reductions from RCTs were converted to glaucoma state transition probabilities using visual field (VF) mean deviation (MD) decline rates from the Early Manifest Glaucoma Trial. Progressive thinning of the retinal nerve fiber layer (RNFL) on OCT imaging related to IOP control warranted further intervention, including adding medication, selective laser trabeculoplasty (SLT), or incisional glaucoma surgery. We estimated whole costs at Medicare rates and obtained utility values for glaucoma states from previous studies. Incremental costs per quality-adjusted life-year (QALY) gained were evaluated at a QALY threshold of $50 000. One-way deterministic sensitivity analysis, scenario analyses, and probabilistic sensitivity analyses addressed parameter uncertainty and demonstrated model robustness. Main Outcome Measures Total costs, QALY, and incremental cost-effectiveness ratio (ICER). Results Over 35 years in the base case, the Hydrus (Ivantis, Inc.) implanted with cataract surgery arm cost $48 026.13 and gained 12.26 QALYs. The iStent inject (Glaukos Corp.) implanted with cataract surgery arm cost $49 599.86 and gained 12.21 QALYs. Cataract surgery alone cost $54 409.25 and gained 12.04 QALYs. Initial nonsurgical management cost $57 931.22 and gained 11.74 QALY. The device arms dominated or were cost-effective compared with cataract surgery alone within 5 years and throughout sensitivity analyses. The iStent inject arm was cost-effective in 94.19% of iterations in probabilistic sensitivity analyses, whereas the Hydrus arm was cost-effective in 94.69% of iterations. Conclusions Implanting the Hydrus Microstent or iStent inject during cataract surgery is cost-effective at a conservative QALY threshold.
Prostate Artery Embolization

Over the past decade, prostate artery embolization (PAE) has emerged as a minimally invasive treatment option for patients suffering from lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Literature over that time has moved from discussion of technique and technical feasibility of the procedure to comparisons of PAE with traditional surgical therapies such as transurethral resection of the prostate (TURP). In most studies of patients undergoing PAE, transfemoral arterial access was obtained to catheterize the prostatic arteries. More recently, the use of transradial access to perform PAE has been described. While technically challenging, the transradial technique offers several potential advantages in appropriately selected patients, which may improve the benefit-risk profile of PAE and improve patient satisfaction. We describe the history and applications of PAE, list the equipment needed to perform PAE, review the procedural steps and technical considerations, and provide a case example, all in the context of transradial access.